Type 2 diabetes in adults

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

at initial diagnosis

1st line – lifestyle changes

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1st line –

lifestyle changes

Management of type 2 diabetes needs to be individualised, taking into account the particular requirements and circumstances of the patient, particularly in the context of multimorbidity.[36]

Diet and lifestyle are central to this management. Offer structured education to the patient (and/or their family members or carers) at and around the time of diagnosis, with annual reinforcement and review.[36]

Ongoing self-management education by a diabetes education nurse or dietitian promotes diabetes self-care and supports beneficial lifestyle changes.[36][103][104][105] This requires general nutrition and health lifestyle knowledge and an individualised nutrition and exercise plan based on an initial assessment and treatment goals. Interventions that enhance self-management can significantly reduce diabetes distress.[106]

Care of adults with type 2 diabetes must include prompt management of all major cardiovascular risk factors to individualised targets. In addition to glucose control, this includes smoking cessation, blood pressure control (see Blood pressure management), lipid control (see Lipid management), consideration of antiplatelet use for patients with high cardiovascular disease risk (see Antiplatelet therapy), and steps to reduce progression of diabetes-related kidney disease (see Add-on pharmacotherapy for patients with chronic kidney disease [CKD]).[36][80][107] If the patient smokes, give advice on smoking cessation and information on accessing smoking cessation services.[36][130] The European Society of Cardiology (ESC) recommends pharmacological therapies (e.g., nicotine replacement therapy, varenicline, bupropion) should be considered, as well as counselling, to improve cessation success rate.[80]

Nutritional advice should be tailored to the needs of the individual patient, and be provided by a healthcare professional with specific expertise and competencies in nutrition.[36] The European Association for the Study of Diabetes (EASD) guidelines for the dietary management of diabetes note that a range of foods and dietary patterns are suitable for diabetes management.[45] The National Institute for Health and Care Excellence (NICE) in the UK and the EASD recommend encouraging the patient to follow the same healthy eating advice as the general population.[36][45] In particular, encourage the patient to include minimally processed, high-fibre, low-glycaemic-index sources of carbohydrate in their diet (e.g., fruit, vegetables, nuts, seeds, wholegrains, and pulses); eat low-fat dairy products and oily fish; limit their intake of foods containing saturated and trans fatty acids; and minimise consumption of red and processed meats, sodium, sugar-sweetened beverages and refined grains.[36][45]

Give individualised recommendations for carbohydrate and alcohol intake, and meal patterns.[36] Reducing the risk of hypoglycaemia should be a particular aim for a person using insulin or an insulin secretagogue.[36]

Encourage an intake of free or added sugars below 10% of total energy intake.[45] Non-nutritive sweeteners can be used to replace sugars in foods and beverages.[34][45]

Although limited substitution of sucrose-containing foods for other carbohydrates in the meal plan is allowable, advise the patient to take care to avoid excess energy intake.[36]

Dietary fibre intake should be at least 35 g/day, with fibre-enriched foods and fibre supplements being considered when sufficient intake cannot be obtained from diet alone.[45]

Discourage the patient from eating food marketed specifically for people with diabetes.[36]

There is ongoing debate about the potential role of low-carbohydrate diets in people with type 2 diabetes. Evidence suggests such diets can be safe and effective in the short term in managing weight, and improving glycaemic control and cardiovascular risk.[109] One meta-analysis found no difference in glucose-lowering effects, weight, or low-density lipoprotein-cholesterol levels between low- and high-carbohydrate diets at 1 year or later.[110] Another meta-analysis concluded there was moderate- to low-quality evidence that some patients can achieve remission of their type 2 diabetes by following a low-carb diet for 6 months.[111] The EASD does not recommend very low-carbohydrate ketogenic diets.[45] The American Diabetes Association (ADA) recommends considering reduction of the overall carbohydrate intake for adults to improve glycaemic control.[34]

A variety of dietary patterns, which encompass some of the key principles outlined above, are recommended by the EASD, including the Mediterranean, Nordic, and vegetarian/vegan diets.[45] Mediterranean or plant-based dietary patterns with high unsaturated fat content are also recommended by the ESC to lower cardiovascular risk, with the former also recommended by the ADA.[34][80] There is growing evidence that Mediterranean and vegetarian/vegan diets improve glycaemia and other cardiometabolic risk factors in people with type 2 diabetes, with the Nordic diet improving BMI and other cardiometabolic risk factors.[45][112][113][114] However, care is required to avoid long-term exclusion of important nutrients.

There is insufficient evidence to recommend the routine use of herbal supplements and micronutrients (e.g., cinnamon, curcumin, vitamin D, aloe vera) to improve glycaemic control in patients with diabetes.[34]

Integrate dietary advice with a personalised diabetes management plan that includes other aspects of lifestyle modification, including increasing physical activity and losing weight.[28][34][115][116][117][118]

Encourage the patient to reduce sedentary behaviour and be more physically active.[34][115] Also encourage the patient to incorporate activity into their daily life (e.g., brisk walking, gardening, cycling).[115][117] In this way, the patient can gradually increase the amount and intensity of activity they do.[115] Advise the patient to do 45-60 minutes of moderate-intensity activity a day, particularly if they do not reduce their energy intake, in order to prevent obesity. Advise people who have been living with obesity and have lost weight that they may need to do 60-90 minutes of activity a day to avoid regaining weight.[117]

A systematic review and meta-analysis of observational studies concluded that physical activity, even below recommended amounts, was associated with reduced incidence of diabetes-related complications.[119]

Both the ADA and the ESC recommend advising patients about optimal minimum weekly levels of aerobic exercise: 150 minutes per week at moderate-intensity, or 75 minutes per week at vigorous-intensity (if there are no contraindications).[34][80] They further recommend that, in addition to aerobic exercise, resistance exercise should be performed at least twice weekly (provided it is not contraindicated) for additional benefit.[34][80] Both advise that all people with diabetes should be encouraged to increase their levels of any physical activity (e.g., walking, gardening, housework, yoga, dancing, swimming) above baseline, even if they do not meet optimal recommended exercise levels.[34][80]

The ESC additionally recommends: adaptation of exercise interventions to comorbidities and/or diabetes complications (e.g., frailty, neuropathy, retinopathy); consideration of behavioural theory-based interventions to encourage exercise behaviours; and the use of structured exercise interventions for patients with established cardiovascular disease (CVD) (with consideration of an exercise stress test prior to initiating a structured exercise programme).[80]

If the patient has overweight, set an initial body weight loss target of 5% to 10%.[36] Evidence suggests that weight loss of >5% in adults with overweight or obesity improves glycaemic control, lipid levels, and blood pressure.[80]

Weight loss management programmes with a healthy eating and physical activity plan resulting in an energy deficit have the potential for type 2 diabetes remission.[45][49][120][121] The EASD recommends a low-energy total diet replacement programme (e.g., 3500 kJ/day [840 kcal/day] for 12-20 weeks), provided by trained health professionals, with carefully adjusted glucose-lowering and antihypertensive medications, to provide sufficient weight loss to induce remission of type 2 diabetes (10% to 15% body weight or greater).[45]

The Diabetes Remission Clinical Trial (DiRECT) of supported weight loss management for people diagnosed with type 2 diabetes within the previous 6 years, and a BMI of 27kg/m² to 45 kg/m², found that almost half of participants achieved remission to a non-diabetic state and were off antidiabetic drugs at 12 months.[120] At 2 years, more than one third of trial participants had sustained remission.[122]

Support the patient with evidence-based treatments to achieve and maintain weight loss. With the aid of trained health professionals, a variety of weight-loss diet types and macronutrient compositions can be used, provided that they meet other dietary recommendations.[45] This includes nutritionally complete low-energy formula products; however, neither extreme high-carbohydrate, nor very low-carbohydrate ketogenic diets are recommended by the EASD.[45] Following success of a pilot scheme, the National Health Service in England is expanding its programme of 3-month total diet replacement soups and shakes for people diagnosed with type 2 diabetes in the last 6 months.[123]

Consider screening for sleep health, including symptoms of sleep disorders, disruption to sleep due to diabetes symptoms or management needs, and worry about sleep.[34] Consider referring to a sleep specialist.[34]

Obesity and diabetes are risk factors for sleep apnoea, and inadequate sleep may affect glycaemic control.[34]

Studies have shown that adherence to a healthy lifestyle (e.g., favourable diet, physical activity, non-smoking, moderate alcohol intake, and normal weight) is associated with a reduced relative risk of mortality in those with type 2 diabetes.[48]

Plus – agree glycaemic (HbA1c) target

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Plus –

agree glycaemic (HbA1c) target

Treatment recommended for ALL patients in selected patient group

HbA1c goals should be individualised at all stages of management, according to the needs and circumstances of your patient; this is particularly important in the context of multimorbidity.[36] Ensure the patient is involved in any decisions about their individual glycaemic target.[36] To determine the most appropriate HbA1c target for your patient, check your local protocols and consult a specialist if needed. Encourage the patient to reach their target and maintain it, unless any resulting adverse effects (including hypoglycaemia), or the effort required to achieve their targets, impairs their quality of life.[36] Individualised HbA1c goals improve quality of life compared with uniform tight control.[139]

In the UK, the National Institute for Health and Care Excellence (NICE) recommends supporting the patient to aim for an HbA1c level of 48 mmol/mol (6.5%) if they manage their type 2 diabetes either with lifestyle and diet, or with lifestyle and diet combined with a single drug not associated with hypoglycaemia.[36] If the patient is on a drug associated with hypoglycaemia, support them to aim for an HbA1c level of 53 mmol/mol (7.0%).[36]

The ESC recommends tight glycaemic control (HbA1c <7.0%; if appropriate/able) to reduce microvascular complications, and they advise to consider the same for reducing coronary artery disease in the long-term (preferably using agents with proven cardiovascular benefit).[80]

Aim to make a routine assessment of frailty whenever you review an older person with diabetes.[83][84][85] Use a validated tool (e.g., the electronic Frailty Index [eFI], the Rockwood frailty score, or Timed Up and Go) to confirm clinical suspicion of frailty.[84][85] Frail patients need a tailored approach to management; de-escalation of therapy is as important as intensification. Specifically bear in mind that glycaemic targets recommended for good control in fit younger people are too tight for frail older patients.[83][84]

Also consider a slightly higher HbA1c level on a case-by-case basis for patients who are unlikely to achieve longer-term risk-reduction benefits (e.g., those with a reduced life expectancy); those for whom intensive management is not appropriate (e.g., people with significant comorbidities); and people for whom tight blood glucose control poses a high risk of the consequences of hypoglycaemia, including people who are at risk of falling, people who have impaired awareness of hypoglycaemia, those who drive or operate machinery as part of their job.[34][36]

If the patient drives, ensure they are aware of the relevant local advice on plasma glucose level. In the UK, the Driver and Vehicle Licensing Agency advises to aim for a level of at least 5 mmol/L (90 mg/dL) before driving.[140]

Self-monitoring of glucose levels may help with self-management and medication adjustment, particularly in people taking insulin. It can give insight into the impact of lifestyle and medication management on blood glucose and symptoms, particularly when combined with education and support; glucose monitoring plans should be individualised.[102]

Traditionally, self-monitoring involves glucose levels being measured from capillary blood samples (self-monitoring of blood glucose, SMBG) that is using finger-stick blood glucose testing.

NICE and the European Association for the Study of Diabetes/American Diabetes Association (EASD/ADA) recommend SMBG as an option for people with type 2 diabetes who are using insulin.[36][102]

NICE also recommends routinely offering SMBG for adults with type 2 diabetes if there is evidence of hypoglycaemic episodes, or the patient is on oral medication that may increase their risk of hypoglycaemia while driving or operating machinery, or the patient is pregnant, or is planning to become pregnant.[36]

NICE suggests considering short-term SMBG in adults with type 2 diabetes (and reviewing treatment as necessary) when starting treatment with oral or intravenous corticosteroids, or to confirm suspected hypoglycaemia.[36]

The newer technology of continuous glucose monitoring (CGM) is now also being used. CGM involves a small, disposable device with a subcutaneous sensor constantly attached to the skin, which measures glucose levels in interstitial fluid, and sends the readings to a display device or smart device.[141] The CGM devices may provide real-time data (rtCGM) or intermittently scanned data (isCGM). CGM can provide more information than SMBG, but it might not be readily available in all regions for people with type 2 diabetes.

NICE recommends offering CGM to adults with type 2 diabetes if they are on multiple daily insulin injections and they have: recurrent hypoglycaemia or severe hypoglycaemia or; impaired hypoglycaemia awareness or; a condition or disability that means they cannot self-monitor their blood glucose by SMBG but could use a CGM device, or; they would otherwise be advised to self-measure at least 8 times a day.[36] NICE also recommends offering CGM to adults with type 2 diabetes if they are insulin-treated and would need help from a care worker or healthcare professional to monitor their blood glucose.[36]

The EASD/ADA also state that CGM provides more information, and has clear advantages over SMBG and may be useful for people with type 2 diabetes, particularly those treated with insulin.[102] CGM use is recommended by the ADA for people with diabetes that are at high risk of hypoglycaemia.[34]

NICE notes that CGM should be provided by a team with expertise in its use, and appropriate patient support and education provided.[36] Capillary blood glucose measurements will still need to be carried out to check the accuracy of the CGM device, and need to be available as a back-up should the CGM device fail.[36]

In practice, unless directed otherwise by a specific clinical need or dosing regimen, allow 3-6 months to assess the impact of any intervention aimed at improving glycaemic control, whether pharmacological or non-pharmacological. Bear in mind that this timeframe will vary on an individual patient basis, and initial blood glucose levels; carefully consider how much of a risk the patient’s HbA1c might pose and step up to more intense interventions more quickly if needed.

If the patient is unable to meet their individualised HbA1c goal with lifestyle interventions, pharmacotherapy is recommended to reduce risk of both microvascular (nephropathy, retinopathy, neuropathy) and macrovascular (coronary artery, cerebrovascular, and peripheral vascular disease) complications.[142][143] See the Acute timeframe.

Consider – blood pressure management

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Consider –

blood pressure management

Additional treatment recommended for SOME patients in selected patient group

Consult your local protocols. Guidelines differ regarding recommended blood pressure (BP) targets for those with type 2 diabetes. In the most recent EUROASPIRE surveys (EAIV 2012/13 and EAV 2016/17), 80% of men and 87% of women with a diagnosis of diabetes also had a history of hypertension.[80] Optimal BP control reduces the risk of both microvascular and macrovascular complications.[80]

The National Institute for Health and Care Excellence (NICE) in the UK recommends maintaining BP with lifestyle changes or drug treatments to targets of below 135/85 mmHg for adults aged under 80 years, based on ambulatory or home BP monitoring (or <140/90 mmHg based on clinic BP).[82] They recommend that BP should be maintained below 145/85 mmHg for patients aged 80 and over, based on ambulatory or home BP monitoring (or <150/90 mmHg based on clinic BP).[82] Further, they advise to target BP below 130/80 mmHg (clinic BP) for patients with CKD and albumin-to-creatinine ratio (ACR) of 70 mg/mmol or more; and below 140/90 mmHg (clinic BP) for those with CKD and ACR <70 mg/mmol.[82]

Although NICE recommends using clinical judgement for patients with frailty or multi-morbidity, their guideline committee concluded that there was no evidence to suggest BP targets should be different in people with type 2 diabetes; therefore, these recommendations for BP targets apply to people with and without type 2 diabetes.[82] NICE also recommends using the same BP targets for people with and without cardiovascular disease.[82] NICE highlights the importance of measuring standing as well as lying/sitting BP in people with type 2 diabetes, based on expert opinion that this group of patients is at higher than usual risk of postural hypotension.[82] If there is a drop in the systolic reading after standing for at least a minute (from lying or sitting) of 20 mmHg or more (or 10 mmHg or more in the diastolic reading), likely causes (including current medicines) should be considered and managed appropriately (e.g., falls prevention measures) and future BPs taken standing.[82] Further specialist evaluation should be considered if symptoms persist despite these measures, or if BP measurements (performed lying and standing) have not confirmed postural hypotension despite symptoms being suggestive.[82] If the patient has a significant postural drop in BP or symptoms of postural hypotension (e.g., falls, postural dizziness), NICE recommends treating hypertension to a target based on standing measurements.[82]

The 2023 ESC guideline on CVD management in diabetes recommends an individualised approach to treating hypertension in people with diabetes: up to the age of 65 years, target systolic BP (SBP) to 130 mmHg, and <130 mmHg if tolerated (but no lower than 120 mmHg); in older people (aged >65 years), target SBP to a range of 130 to 139 mmHg.[80] They further advise that BP targeted to <130 mmHg may be considered to further reduce the risk of stroke in patients who have a particularly high risk of a cerebrovascular event.[80]

Regardless of the specific BP goal, both lifestyle changes and antihypertensive medication may be needed to achieve BP control. Reduced sodium intake (to <100 mmol/day) and high intake of fruit, vegetables, and low-fat dairy products have all been shown to improve BP control.[80] These lifestyle measures are supported by the ESC for people with type 2 diabetes and hypertension, in addition to alcohol restriction, increased exercise, and weight loss where appropriate.[80]

Specific drug regimens for the management of hypertension are beyond the scope of this topic. Consult local protocols or guidelines for guidance on drug and dose selection.

In the UK, NICE recommends a stepwise approach to pharmacological treatment of hypertension in people without CKD, or with CKD and an ACR ≤30 mg/mmol (ACR categories A1 and A2).[82][86] For recommendations on choice of hypertensive agent in people with CKD and an ACR >30 mg/mmol (ACR category A3 or above). See Add-on pharmacotherapy for patients with CKD.

Step 1: for initial treatment, give an ACE inhibitor or an angiotensin-II receptor antagonist. If an ACE inhibitor is not tolerated, use an angiotensin-II receptor antagonist instead. Do not combine an ACE inhibitor with an angiotensin-II receptor antagonist. Use an angiotensin-II receptor antagonist in preference to an ACE inhibitor if the patient is of black African or African-Caribbean family origin.[82]

Step 2: if hypertension remains uncontrolled on first-line therapies, discuss, and support, adherence with antihypertensive medication. Step up to dual therapy by offering the choice of either a calcium-channel blocker or a thiazide-like diuretic in addition to step 1 treatment.[82]

Step 3: before considering next step treatment, discuss adherence with the patient and review their medications to ensure these are being taken at optimal tolerated doses. If the patient’s BP remains uncontrolled despite step 2 therapies, offer a triple therapy combination of an ACE inhibitor or an angiotensin-II receptor antagonist, and a calcium-channel blocker, and a thiazide-like diuretic.[82]

Step 4: if BP is not controlled despite optimal tolerated doses of the triple-therapy medications in step 3, regard the patient as having resistant hypertension.[82] Before considering further treatment, confirm elevated clinic blood pressure measurements using ambulatory or home blood pressure recordings, assess for postural hypotension, and discuss adherence.[82] For people with confirmed resistant hypertension, consider adding a fourth antihypertensive drug or refer these patients to a hypertension specialist.[82] Also consider possible secondary causes of hypertension (e.g., Conn’s adenoma, phaeochromocytoma, renovascular hypertension): in people with signs and symptoms suggesting a secondary cause, consider the need for specialist investigations and/or referral. Patients whose BP is still uncontrolled on four antihypertensive drugs should be referred to a specialist.[82]

For people with cardiovascular disease, follow the recommendations for disease-specific indications in the NICE guideline for their condition. If their BP remains uncontrolled, offer antihypertensive drug treatment in line with the stepwise therapy outlined above.[82]

The ESC guideline takes a broadly similar approach to NICE but highlights additional key messages.[80] It states that there is strong evidence to support the use of an ACE inhibitor or angiotensin-II receptor antagonist, particularly in patients who have microalbuminuria, proteinuria, or left ventricular hypertrophy; these drugs have renoprotective properties that go beyond their antihypertensive effects alone.[80] The ESC recommends dual therapy as first-line treatment because most patients will not achieve BP control on a single antihypertensive medication.[80] These may be administered as a proprietary combination formulation (if available) to improve adherence and achieve quicker BP control.[80] Beta-blockers should be considered at any step in hypertension treatment if there is a specific indication (e.g., coronary artery disease, atrial fibrillation, heart failure).[80]

There is an increasing drive to incorporate the use of home BP monitoring into the diagnosis and management of hypertension in adults, including those with diabetes.[34][124]

Consider – lipid management

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Consider –

lipid management

Additional treatment recommended for SOME patients in selected patient group

Consult your local protocols. Guidelines recommend differing approaches to lipid-modification therapy.

In the UK, the National Institute for Health and Care Excellence (NICE) recommends using a validated risk assessment tool such as QRISK3 to assess cardiovascular disease (CVD) risk within the next 10 years in people with type 2 diabetes aged between 25 and 84 years (those aged 85 years and over should be considered at increased CVD risk due to age alone, especially if they smoke and/or have elevated blood pressure).[125] QRISK®3 calculator Opens in new window (In its guideline on type 2 diabetes [last updated in 2022], NICE recommends using QRISK2 to assess cardiovascular disease risk in adults with type 2 diabetes.[36] However, NICE’s 2023 guideline on CVD recommends using QRISK3.[125] NICE acknowledges that it may be necessary to use QRISK2 until electronic clinical systems are updated with QRISK3.[125] Depending on local availability, either QRISK2 or QRISK3 is a reasonable tool for assessing CVD risk in adults with type 2 diabetes. NICE does specify certain populations for whom QRISK3 should be used [including, but not limited to, those with severe mental illness, or those taking atypical antipsychotics or corticosteroids] as QRISK2 may underestimate CVD risk in these patients.[125] NICE also notes that CVD risk tools [including QRISK3] may underestimate risk in some groups [e.g., those treated for HIV, those who have recently stopped smoking, etc.] and emphasise that clinical judgement is needed to interpret risk scores.[125]) NICE does not recommend use of a risk assessment tool for people at high risk of CVD, including those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and/or albuminuria, or an inherited disorder of lipid metabolism (e.g., familial hypercholesterolaemia).[125]

Use high-intensity statin therapy (i.e., atorvastatin at the low end of the high-intensity dose range) for the primary prevention of CVD for people with (and without) type 2 diabetes who have ≥10% 10-year risk (estimated using QRISK3) of developing CVD.[125] NICE notes not to rule out treatment with atorvastatin for primary prevention just because the patient’s 10-year risk score is less than 10% if they have an informed preference for taking a statin or there is concern the risk may be underestimated.[125] NICE also recommends considering this treatment for people aged 85 years and older, with an awareness for the factors that may make treatment inappropriate (e.g., life expectancy, frailty, comorbidities, or other current medicines).[125]

Use high-intensity statin therapy (i.e., atorvastatin at the high end of the high-intensity dose range) for secondary prevention for people with (and without) diabetes with established CVD, irrespective of their cholesterol level and provided they have normal renal function.[125] A lower dose should be offered for secondary prevention if the person is at high risk of adverse effects from statins or they are taking other drugs that could interact with the statin, or they have a preference for a lower dose.[125] People with CKD who require secondary prevention of CVD should be offered atorvastatin at the low end of the high-intensity dose range (i.e., the same as for primary prevention).[125]

The decision to start (or escalate) lipid-lowering therapy should be made with the patient following an informed discussion about the risks and benefits of treatment, with consideration of individual patient factors (e.g., preferences, comorbidities, other medicines).[125] Statins are contraindicated in pregnancy: statins should be stopped 3 months before the patient attempts to conceive and should not be restarted until breastfeeding is finished.[125]

Before starting lipid-modification therapy, a clinical assessment should be carried out, including review of smoking and diabetes status, alcohol consumption, BP, and BMI (or other measure of obesity).[125] Baseline blood tests should be performed, including renal function, a liver transaminase level, and a full lipid profile (i.e., total cholesterol and high-density lipoprotein [HDL]-cholesterol and triglyceride levels, from which non-HDL and low-density lipoprotein [LDL]-cholesterol are calculated; a fasting sample is not needed).[125] Blood tests for thyroid-stimulating hormone (TSH) level should be requested if there are symptoms of thyroid dysfunction, and creatinine kinase levels should be performed if the person has had persistent generalised unexplained muscle symptoms (pain, tenderness, or weakness).[125] Clinical findings, full lipid profile, and family history should be used to assess likelihood of a familial lipid disorder (instead of basing the decision on lipid values alone).[125] Familial lipid disorders are outside the scope of this topic: for more information about when to suspect and how to diagnose familial hypercholesterolaemia, see Hypercholesterolaemia. Arrange for specialist assessment of people with a total cholesterol concentration of more than 9.0 mmol/L or a non-HDL-cholesterol concentration of more than 7.5 mmol/L even in the absence of a first-degree family history of premature coronary heart disease.[125]

Comorbidities and secondary causes of dyslipidaemia should be treated (and if appropriate, lifestyle changes discussed) at the same time as initiation of statin therapy for secondary prevention (or before starting a statin for primary prevention).[125]

Consistent data have demonstrated the efficacy of statins in preventing cardiovascular events and reducing cardiovascular mortality in patients with diabetes, with no evidence for sex differences; their use is associated with a limited number of adverse events.[80]

In terms of monitoring, NICE recommends that, 2-3 months after initiating or changing a lipid-lowering treatment, a full lipid profile and liver transaminase level should be performed (liver transaminase should be checked again at 12 months; no further repeat liver transaminase tests are then necessary unless clinically indicated).[125] In those on a statin for primary prevention, aim for a greater than 40% reduction in non-HDL-cholesterol, and in those using a statin for secondary prevention, aim for LDL-cholesterol of 2.0 mmol/L or less (or non-HDL-cholesterol of 2.6 mmol/L or less).[125] If the appropriate lipid target is not achieved, discuss adherence and timing of dose, optimise adherence to diet and lifestyle measures, and consider increasing the statin intensity/dose if appropriate.[125] If the person has CKD and eGFR is 30 mL/min/1.73 m² or more, the dose of atorvastatin should be increased (if eGFR is <30 mL/min/1.73 m², any dose increase should be agreed with a renal specialist).[125]

If adverse effects are reported with high-intensity statin therapy, consider the following options with the patient: stop the statin and reintroduce it once symptoms resolve to check if they are statin-related; or change to an alternative high-intensity statin; or reduce the dose; or change to a lower-intensity statin.[125]

NICE recommends reviewing lipid-lowering medication annually.[125] Use these reviews to discuss medication adherence and lifestyle modification and to address CVD risk factors.[125] Those on secondary prevention should be offered an annual full lipid profile to inform the discussion (and this should also be considered for those on primary prevention).[125] Do not stop statins because of an increase in blood glucose level or HbA1c.[125]

The ESC guidelines recommend screening patients with diabetes for severe target organ damage (TOD) and assessing for symptoms and medical history suggestive of atherosclerotic cardiovascular disease (ASCVD) to understand their cardiovascular risk.[80] Where neither symptomatic ASCVD nor severe TOD are present, they recommend use of the SCORE2-Diabetes tool to estimate 10-year CVD risk.[80] The ESC categorises patients with type 2 diabetes according to these assessments into cardiovascular risk groups (very high, high, moderate, and low risk) which are used to guide management.[80] Based on these categories, the ESC recommends for patients with type 2 diabetes who are at moderate cardiovascular risk: a low-density lipoprotein (LDL)-cholesterol target of <2.6 mmol/L (<100 mg/dL).[80] For patients who are at high cardiovascular risk, the ESC recommends an LDL-cholesterol target of <1.8 mmol/L (<70 mg/dL) and LDL-cholesterol reduction of at least 50%, and a secondary goal of a non-HDL-cholesterol target of <2.6 mmol/L (<100 mg/dL).[80] For those at very high cardiovascular risk, the ESC recommends an LDL-cholesterol target of <1.4 mmol/L (<55 mg/dL) and LDL-cholesterol reduction of at least 50%, and a secondary goal of a non-HDL-cholesterol target of <2.2 mmol/L (<85 mg/dL).[80]

The ESC recommends statins as first-line lipid-lowering treatment in patients with diabetes and high LDL-cholesterol levels.[80] The cardiovascular risk profile (very high, high, moderate) of the individual patient and the corresponding LDL-cholesterol (or non-HDL-cholesterol) target levels should be used to determine statin administration.[80] The ESC recommends intensive LDL-cholesterol lowering with statins for those with CKD.[80]

Specific regimens for other lipid-lowering therapies are outside the scope of this topic: refer to Hypercholesterolaemia for more information. The following is general guidance.

Both NICE and ESC guidelines recommend that if the appropriate lipid target in a person with established ASCVD is not reached on maximum tolerated statin therapy, intensification of lipid-lowering therapy (i.e., additional lipid-lowering therapies) should be considered on an individual basis in collaboration with the patient.[80][125]

For some patients with diabetes and established CVD who have persistently elevated LDL-cholesterol despite maximally-tolerated statin therapy, addition of ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor monoclonal antibody may confer clinical benefit.[80][126]Giugliano RP, Cannon CP, Blazing MA, et al; IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2018 Apr 10;137(15):1571-82.[127][128][129] The BMJ: PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations Opens in new window

Further, NICE recommends considering the addition of ezetimibe (to maximum tolerated statin therapy) in patients with established CVD to further reduce their CVD risk even if the lipid target for secondary prevention is met with a statin alone.[125] The ESC recommends a statin plus ezetimibe combination therapy for patients not meeting their target LDL-cholesterol on statin therapy alone (there is no specification of CV risk category given for this recommendation), or as an option for intensive LDL-cholesterol lowering in patients with diabetes and CKD.[80]

Other lipid-lowering therapies should also be considered on an individual basis if statin therapy is contraindicated, or is not tolerated at any intensity/dose, and may be required in addition to statin therapy if the patient has additional indications for lipid-lowering treatment (e.g., hypertriglyceridaemia, a familial lipid disorder).[80][125]

Specific drug regimens for the management of hyperlipidaemia are beyond the scope of this topic. Consult local protocols or guidelines for guidance on drug and dose selection.

Consider – antiplatelet therapy

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Consider –

antiplatelet therapy

Additional treatment recommended for SOME patients in selected patient group

People with type 2 diabetes and cardiovascular disease (CVD) will need antiplatelet therapy for secondary prevention. This will usually be in the form of low-dose aspirin or clopidogrel.[80] Antiplatelet therapy has been found to reduce the risk of stroke, myocardial infarction, or vascular death.[131]

The role of antiplatelets in primary prevention of CVD is unclear and guidelines differ in their recommendations. Consult your local protocols.

The National Institute for Health and Care Excellence in the UK recommends against routine antiplatelet therapy (aspirin or clopidogrel) as primary prevention for adults with type 2 diabetes without cardiovascular disease.[36][125] This is because the increased risk of major bleeding is considered to outweigh any potential benefits from primary prevention.[132] The ASCEND trial comparing low-dose aspirin with placebo among 15,480 adults with diabetes but no evident CVD found that the benefits of aspirin use in preventing serious vascular events was largely counterbalanced by the increased risk of major bleeding events over a mean follow-up of 7.4 years.[133]

However, the ESC recommends that low-dose aspirin can be considered for prevention of the first severe vascular event in adults with type 2 diabetes without a history of symptomatic ASCVD or revascularisation, provided there are no clear contraindications.[80] They acknowledge that therapy should be individualised, as those with a higher cardiovascular risk may benefit more from antiplatelet therapy.[80] They recommend the use of low-dose aspirin in patients with CKD and ASCVD.[80] The ESC also recommends that concomitant use of an appropriate proton-pump inhibitor should be considered (based on the individual bleeding risk of the patient) for patients taking a single antiplatelet drug (e.g., low-dose aspirin), to reduce the gastrointestinal bleeding risk highlighted by the ASCEND trial (in which three-quarters of patients were not taking a proton-pump inhibitor).[80] They make the same recommendation for those taking a single anticoagulant.[80] Further, they recommend that an appropriate proton-pump inhibitor is used when a combination of antithrombotic drugs is being taken.[80]

Consider – add-on pharmacotherapy for patients with CKD

Back

Consider –

add-on pharmacotherapy for patients with CKD

Additional treatment recommended for SOME patients in selected patient group

If your patient has chronic kidney disease (CKD) or develops it at any point post-diagnosis, NICE recommends to give an angiotensin-II receptor antagonist or an ACE inhibitor (titrated to the highest licensed dose that the person can tolerate) if albumin-to-creatinine ratio (ACR) is 3 mg/mmol or more (i.e., clinically important proteinuria).[36][86]

Give a sodium-glucose cotransporter-2 (SGLT2) inhibitor (in addition to the angiotensin-II receptor antagonist or ACE inhibitor) if the patient is already taking an angiotensin-II receptor antagonist or an ACE inhibitor (titrated to the highest licensed dose that they can tolerate), ACR is over 30 mg/mmol, and the patient meets the criteria in the marketing authorisation (including relevant estimated glomerular filtration rate [eGFR] thresholds).[36]

Consider an SGLT2 inhibitor (in addition to the angiotensin-II receptor antagonist or ACE inhibitor) if the patient is already taking an angiotensin-II receptor antagonist or an ACE inhibitor (titrated to the highest licensed dose that they can tolerate), ACR is between 3 and 30 mg/mmol, and the patient meets the criteria in the marketing authorisation (including relevant estimated glomerular filtration rate [eGFR] thresholds).[36]

If the patient has stage 3 or stage 4 CKD (i.e., with an eGFR <60 mL/min/1.73 m²) associated with type 2 diabetes with albuminuria, consider finerenone (a non-steroidal mineralocorticoid receptor antagonist) if it is used as an add-on to optimised standard care (which should include, unless they are unsuitable, the highest tolerated licensed doses of ACE inhibitors or angiotensin-II receptor antagonists and SGLT2 inhibitors) and the patient has an eGFR of ≥25 mL/min/1.73 m².[134]

If the patient has CKD with an ACR ≤30 mg/mmol (ACR categories A1 and A2) and requires an antihypertensive agent follow the recommendations outlined in Blood pressure management section, which also apply to people without CKD.[86]

If the patient has CKD and an ACR >30 mg/mmol (ACR category A3 or above) and requires an antihypertensive agent give an angiotensin-II receptor antagonist or an ACE inhibitor (titrated to the highest licensed dose that the person can tolerate).[86]

Where possible, treat hypertension in people with CKD with drugs taken only once daily.[82]

These drugs should be added to optimised standard care (as outlined in the Acute timeframe).

SGLT2 inhibitors are not suitable for everyone and should only be used within their marketing authorisation; some SGLT2 inhibitors are not licensed for this indication in some regions, including the UK.[36]

These recommendations from NICE are based on evidence from randomised controlled trials (RCTs) which showed that SGLT2 inhibitors reduce the risk of CKD progression, mortality and cardiovascular events in adults with type 2 diabetes and CKD.[36][Evidence A] RCTs also showed that angiotensin-II receptor antagonists reduce the risk of end-stage renal disease and heart failure, as well as no clear difference between ACE inhibitors and angiotensin-II receptor antagonists on a number of outcomes, including end-stage renal disease, all-cause mortality, cardiovascular mortality, and hospitalisation.[86]

Pharmacotherapy recommendations for patients with type 2 diabetes and CKD provided by the Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline are largely aligned with the NICE guidelines outlined above.[135] They also suggest that a non-steroidal mineralocorticoid receptor antagonist with proven kidney or cardiovascular benefit be considered for patients with type 2 diabetes, eGFR ≥25 mL/min/1.73 m², normal serum potassium concentration, and clinically important proteinuria, despite maximum tolerated dose of an angiotensin-II receptor antagonist or an ACE inhibitor.[135]

The United Kingdom Kidney Association (UKKA) in 2023 recommends use of an SGLT2 inhibitor in people with type 2 diabetes and CKD (irrespective of primary kidney disease, but excluding those with polycystic kidney disease or kidney transplant recipients) who have: an eGFR of 20-45 mL/min/1.73 m²; or an eGFR of >45 mL/min/1.73 m² and a urinary albumin-to-creatinine ratio (uACR) of ≥25 mg/mmol (urinary protein-to-creatinine ratio of 35 mg/mmol can be considered equivalent); or symptomatic heart failure, irrespective of ejection fraction; or established coronary disease.[136] The UKKA also suggests that, in people with type 2 diabetes and CKD (excluding kidney transplant recipients), an SGLT2 inhibitor should be: initiated if eGFR is >45-60 mL/min/1.73 m² and uACR is <25 mg/mmol to modify cardiovascular risk and slow rate of kidney function decline (recognising that effects on glycaemic control will be limited); or considered if eGFR is <20 mL/min/1.73 m² to slow kidney disease progression.[136] The UKKA recommends that SGLT2 inhibitors are continued until renal replacement therapy is required.[136]

The 2023 ESC guidelines on CVD management in diabetes recommend treating patients with type 2 diabetes and CKD with an SGLT2 inhibitor and/or finerenone, since these reduce cardiovascular risk and kidney failure risk on top of standard care (e.g., ACE inhibitor or angiotensin-II receptor antagonist).[80] Specifically, in addition to use of an ACE inhibitor or angiotensin-II receptor antagonist they recommend use of: an SGLT2 inhibitor (proven to reduce CV and kidney failure risk) when eGFR is ≥20 mL/min/1.73 m²; finerenone (with appropriate potassium monitoring) when eGFR is >60 mL/min/1.73 m² and uACR is ≥30 mg/mmol, or when eGFR is 25-60 mL/min/1.73 m² and uACR is ≥3 mg/mmol.[80]

The ESC also makes recommendations in a 2023 update to their heart failure guidelines for SGLT2 inhibitors and finerenone in patients with type 2 diabetes and CKD to reduce the risk of heart failure hospitalisation (both SGLT2 inhibitors and finerenone) or cardiovascular death (SGLT2 inhibitors).[137]

with symptomatic hyperglycaemia

Plus – insulin or sulfonylurea

Back

Plus –

insulin or sulfonylurea

Treatment recommended for ALL patients in selected patient group

If an adult with type 2 diabetes is symptomatically hyperglycaemic at initial diagnosis (or at any subsequent time during treatment), consider rescue therapy with insulin or a sulfonylurea, and review treatment when blood glucose control has been achieved.[36]

ACUTE

HbA1C above goal: non-pregnant

not at high cardiovascular disease risk

1st line – metformin

Back

1st line –

metformin

In line with global trends, NICE now recommends an approach to managing type 2 diabetes that moves away from one that focuses solely on achieving individualised HbA1c targets, to one which incorporates therapies that not only reduce blood glucose levels, but have proven cardiovascular and renal benefits.[36] The recommendations in this topic are based primarily on the NICE approach.

Determine whether the patient has chronic heart failure or established atherosclerotic cardiovascular disease, or is at high risk of developing cardiovascular disease (using QRISK2/3), and use this assessment to tailor drug treatment.[36] (For more information on global treatment strategies and assessing cardiovascular risk, see Management approach).

Give metformin as first-line drug treatment to all adults with type 2 diabetes.[36]

The dose of immediate-release metformin should be gradually increased over several weeks to minimise the risk of gastrointestinal adverse effects.[36] If gastrointestinal disturbance occurs with immediate-release metformin, a modified-release formulation can be used instead.[36] However, modified-release metformin is associated with statistically worse but likely clinically similar HbA1c lowering and minimal improvement of gastrointestinal intolerance compared to immediate-release metformin.[151]

Metformin may be safely used (with a possible dose reduction) in patients with reduced estimated glomerular filtration rates (eGFRs) with careful monitoring, but it is contraindicated if eGFR is <30 mL/min/1.73 m².[34][102][135][166] In patients with CKD, other options may be considered as an alternative to metformin - see Management approach for more detail.

Gastrointestinal adverse effects are common with metformin.[102] Decreased/deficient vitamin B12 levels are also a recognised common side effect of treatment, especially in those receiving a higher dose or longer treatment duration and in those with existing risk factors.[167] Monitoring at regular intervals is recommended.[102]

For further details about the clinical properties of metformin, see Clinical properties of specific antihyperglycaemic agents in the Management approach.

Primary options

metformin: 500 mg orally (immediate-release) once daily for at least one week, followed by 500 mg twice daily for at least one week, then 500 mg three times daily thereafter, maximum 2000 mg/day

Plus – lifestyle measures and cardiovascular risk reduction

Back

Plus –

lifestyle measures and cardiovascular risk reduction

Treatment recommended for ALL patients in selected patient group

Management of type 2 diabetes needs to be individualised, taking into account the particular requirements and circumstances of the patient, particularly in the context of multimorbidity.[36]

Care of adults with type 2 diabetes must include prompt management of all major cardiovascular risk factors to individualised targets. In addition to glucose control, this includes smoking cessation, blood pressure control, lipid control, consideration of antiplatelet use for patients with high cardiovascular disease risk, and steps to reduce progression of diabetes-related kidney disease.[36][80][107] If the patient smokes, give advice on smoking cessation and information on accessing smoking cessation services.[36][130] The ESC recommends pharmacological therapies (e.g., nicotine replacement therapy, varenicline, bupropion) should be considered, as well as counselling, to improve cessation success rate.[80]

For more detail on lifestyle measures, cardiovascular risk reduction, and pharmacological considerations for people with CKD, see the Initial timeframe.

Consider – bariatric surgery

Back

Consider –

bariatric surgery

Additional treatment recommended for SOME patients in selected patient group

The World Gastroenterology Organisation and International Federation for the Surgery of Obesity and Metabolic Diseases guidelines on obesity note that bariatric surgery is the most effective long-term treatment for obesity and many of its associated health conditions.[28] Sleeve gastrectomy and Roux-en-Y gastric bypass are currently the most commonly performed bariatric procedures worldwide.[28] A comprehensive medical, psychological, and nutritional evaluation involving a multi-disciplinary team should be completed before bariatric surgery is considered, to determine patient suitability and identify any issues that need addressing; lifelong follow-up, as well as cessation of tobacco, alcohol and drugs, is also required[28]

Guidelines from NICE recommend offering an expedited assessment for bariatric surgery to anyone with a BMI of 35kg/m² or over who has recent-onset type 2 diabetes (diagnosis within last 10 years) as long as they are also receiving, or will receive, assessment by a specialist weight-management team.[117] NICE also recommends considering an expedited assessment for bariatric surgery for anyone with a BMI of 30 to 34.9 kg/m² who has recent-onset type 2 diabetes as long as they are also receiving, or will receive, assessment in a specialis weight-management team.[117] In addition, an expedited assessment for bariatric surgery should be considered for anyone of South Asian, Chinese, other Asian, Middle Eastern, black African, or African-Caribbean family background, who has recent-onset type 2 diabetes using a lower BMI threshold (reduced by 2.5 kg/m²) than other populations; these groups are prone to central adiposity and their cardiometabolic risk occurs at a lower BMI.[117]

The 2022 ADA/EASD consensus guideline recommends bariatric surgery should be considered as an option for adults with type 2 diabetes who are appropriate surgical candidates who have: a BMI ≥40.0 kg/m² if of non-Asian ancestry; a BMI ≥37.5 kg/m² if of Asian ancestry; or a BMI of 35.0 to 39.9 kg/m² (32.5 to 37.4 kg/m² if of Asian ancestry) if they cannot achieve durable weight loss and improvement in comorbidities (including hyperglycaemia) with non-surgical methods.[102]

Further, the ESC recommends that bariatric surgery should be considered for patients at high or very high CVD risk with BMI ≥35 kg/m² when repetitive and structured efforts of lifestyle changes combined with weight-reducing medicines do not result in maintained weight loss.[80]

Randomised clinical trials have shown a benefit from bariatric surgery compared with medical therapy alone with regard to diabetes remission, glycaemic control, need for glucose-lowering medications, quality of life, and reduction in cardiovascular risk factor markers over the short term (e.g., 1-3 years) in people with type 2 diabetes, as well as for possible prevention of type 2 diabetes.[28][244][245][246][247][248][249]

Cohort studies suggest that both Roux en Y bypass and sleeve gastrectomy procedures lead to diabetes remission that lasts a mean of about 5 years in more than half of patients, and significantly reduce mortality, stroke, myocardial infarction, and microvascular complications in those with type 2 diabetes.[250][251][252] A systematic review and meta-analysis of randomised-controlled trials concluded that Roux-en-Y bypass resulted in a higher rate of type 2 diabetes remission compared with sleeve gastrectomy after 1 year, but that remission rates did not differ in studies with a 2- and 5-year follow-up.[253]

Compared with sleeve gastrectomy, Roux en Y leads to somewhat greater weight loss and other benefits, but is a more technically challenging operation with higher re-operation and readmission rates.

The benefits and risks of bariatric surgery also vary substantially across type 2 diabetes patient subgroups. In observational studies, average benefits appear to be highest in people with more recent onset of type 2 diabetes, and those not on insulin therapy.[254][255] Benefits have been documented in younger people (age 40-50 years) as well as those over 65 years of age.[254][255]

Bariatric surgery procedures, in particular Roux-en-Y gastric bypass, have been associated with subsequent alcohol-related complications.[28][256] It is important to take this into account when selecting patients for these procedures, and to consider alcohol-related counselling.[256]

2nd line – dipeptidyl peptidase-4 (DPP-4) inhibitor or pioglitazone or sulfonylurea or sodium-glucose cotransporter-2 (SGLT2) inhibitor

Back

2nd line –

dipeptidyl peptidase-4 (DPP-4) inhibitor or pioglitazone or sulfonylurea or sodium-glucose cotransporter-2 (SGLT2) inhibitor

If metformin is contraindicated or not tolerated, consider using one of the following drugs instead of metformin: a DPP-4 inhibitor; or pioglitazone; or a sulfonylurea; or an SGLT2 inhibitor.[36]

Choice of agents should be individualised, taking into account patient preferences, needs, and clinical circumstances (e.g., weight, comorbidities, risks of complications), the effectiveness of the agent in terms of metabolic response and cardiovascular and renal protection, adverse effects, and other factors.[36][80][102] Special considerations should also be given to those with type 2 diabetes and chronic kidney disease.[36] The most appropriate drug regimens for a frail patient, including choice of drug and optimal dose, will need careful consideration and are likely to differ from those recommended for younger, fit patients.[83] 'Start low and go slow' when dosing and titrating medications in frail older adults.[83] Balance the intended benefit of treatment against the risk of adverse treatment effects.[108] The ADA recommends use of medicines with low hypoglycaemia risk for older adults, and deintensification and/or simplification of treatment plans (within individualised glycaemic goals) in this population when the harms or burdens of treatment may outweigh the benefits.[34]

An SGLT2 inhibitor is recommended in some people: those in whom metformin is contraindicated or not tolerated, when diet and exercise alone do not provide adequate glycaemic control, only if a DPP-4 inhibitor would otherwise be prescribed and a sulfonylurea or pioglitazone is not appropriate.[152][153] Before starting treatment with an SGLT2 inhibitor, always check whether the patient is at an increased risk of diabetic ketoacidosis (DKA), for example if they have had a previous episode of DKA, they are unwell with intercurrent illness, or the patient is following a very low carbohydrate or ketogenic diet.[36] In addition, before starting treatment with an SGLT2 inhibitor, advise the patient of the risk of DKA and address modifiable risk factors for DKA, for example, those who are following a very low carbohydrate or ketogenic diet may need to delay treatment until they have changed their diet.[34][36]

DPP-4 inhibitors can be used in cases of renal impairment, although dose adjustment may be required.[102]

Pancreatitis has been reported in clinical trials of DPP-4 inhibitors, but causality has not been established; the drugs should be discontinued if pancreatitis is suspected. Recent analyses have suggested that DPP-4 inhibitors are associated with an increased risk of acute liver injury (compared with SGLT-2 inhibitors) in patients with type 2 diabetes.[229] In addition, the FDA adverse event reporting system noted that there were consistent signals of gallbladder- or biliary-related events associated with DPP-4 inhibitors with real-world data, and that clinicians should be aware of these in clinical practice.[230] Saxagliptin may be associated with an increased risk of hospitalisation for heart failure (and is therefore not recommended by the ESC for use in patients with heart failure).[80][102][227] In a small trial, vildagliptin was found to be associated with increased left ventricular volumes (of unknown clinical significance), but no significant effect on left ventricular ejection fraction (LVEF) was demonstrated.[80][228] Joint pain is a potential rare adverse event associated with DPP-4 inhibitors.[102]

Pioglitazone has been associated with fluid retention, congestive heart failure, weight gain, and bone fracture.[102][164] The ESC does not recommend use of pioglitazone in patients at risk of, or with a history of, heart failure, due to its association with an increased risk of incident heart failure in patients with diabetes.[80] Use of pioglitazone is associated with a small increased risk of bladder cancer.[234]

Sulfonylureas should be used with caution in people at risk of hypoglycaemia.[102]

SGLT-2 inhibitors are associated with an increased risk of mycotic genital infections (usually mild and treatable), and an increased risk of diabetic ketoacidosis (although the incidence is low).[73][102][192][193][194][195] The US Food and Drug Administration (FDA) has issued a warning of the risk of acute kidney injury with canagliflozin and dapagliflozin.[196] The MHRA and European Medicines Agency (EMA) warn of an increased risk of lower-limb amputation (mainly toes) in patients with type 2 diabetes taking canagliflozin, and the MHRA emphasises the importance of preventive foot care for all patients with diabetes.[197][198] Therefore, patients with foot ulcers or at high risk for amputation should be given comprehensive foot-care education while treating with SGLT2 inhibitors. The EASD/ADA guidelines on the management of hyperglycaemia in type 2 diabetes notes that while early studies highlighted potential SGLT2 inhibitor-related safety concerns, including acute kidney injury and amputation, longer-term studies that have prospectively assessed and monitored these events have not seen a significant imbalance in risks.[102][199] The MHRA and FDA also warn of cases of necrotising fasciitis of the perineum (also known as Fournier's gangrene) observed in post-marketing surveillance of SGLT2 inhibitors.[200][201]

For further details about the clinical properties of the drugs discussed here, see Clinical properties of specific antihyperglycaemic agents in the Management approach.

Primary options

DPP-4 inhibitor

alogliptin: 25 mg orally once daily

DPP-4 inhibitor

linagliptin: 5 mg orally once daily

DPP-4 inhibitor

saxagliptin: 5 mg orally once daily

DPP-4 inhibitor

sitagliptin: 100 mg orally once daily

DPP-4 inhibitor

vildagliptin: 50 mg orally twice daily

Thiazolidinedione

pioglitazone: 15-30 mg orally once daily initially, adjust dose according to response, maximum 45 mg/day

Sulfonylurea

gliclazide: 40-80 mg orally (immediate-release) once daily initially, adjust dose according to response, maximum 320 mg/day; 30 mg orally (modified-release) once daily initially, adjust dose according to response, maximum 120 mg/day

Sulfonylurea

glimepiride: 1 mg orally once daily initially, adjust dose according to response, maximum 4-6 mg/day

SGLT2 inhibitor

canagliflozin: 100 mg orally once daily initially, adjust dose according to response, maximum 300 mg/day

SGLT2 inhibitor

dapagliflozin: 10 mg orally once daily

SGLT2 inhibitor

empagliflozin: 10 mg orally once daily initially, adjust dose according to response, maximum 25 mg/day

SGLT2 inhibitor

ertugliflozin: 5 mg orally once daily initially, adjust dose according to response, maximum 15 mg/day

Plus – lifestyle measures and cardiovascular risk reduction

Back

Plus –

lifestyle measures and cardiovascular risk reduction

Treatment recommended for ALL patients in selected patient group

Management of type 2 diabetes needs to be individualised, taking into account the particular requirements and circumstances of the patient, particularly in the context of multimorbidity.[36]

Care of adults with type 2 diabetes must include prompt management of all major cardiovascular risk factors to individualised targets. In addition to glucose control, this includes smoking cessation, blood pressure control, lipid control, consideration of antiplatelet use for patients with high cardiovascular disease risk, and steps to reduce progression of diabetes-related kidney disease.[36][80][107] If the patient smokes, give advice on smoking cessation and information on accessing smoking cessation services.[36][130] The ESC recommends pharmacological therapies (e.g., nicotine replacement therapy, varenicline, bupropion) should be considered, as well as counselling, to improve cessation success rate.[80]

For more detail on lifestyle measures, cardiovascular risk reduction, and pharmacological considerations for people with CKD, see the Initial timeframe.

Consider – bariatric surgery

Back

Consider –

bariatric surgery

Additional treatment recommended for SOME patients in selected patient group

Guidelines from NICE recommend offering an expedited assessment for bariatric surgery to anyone with a BMI of 35 kg/m² or over who has recent-onset type 2 diabetes (diagnosis within last 10 years) as long as they are also receiving, or will receive, assessment by a specialist weight-management team.[117] NICE also recommends considering an expedited assessment for bariatric surgery for anyone with a BMI of 30 to 34.9 kg/m² who has recent-onset type 2 diabetes as long as they are also receiving, or will receive, assessment in a specialist weight-management team.[117] In addition, an expedited assessment for bariatric surgery should be considered for anyone of South Asian, Chinese, other Asian, Middle Eastern, black African, or African-Caribbean family background, who has recent-onset type 2 diabetes using a lower BMI threshold (reduced by 2.5 kg/m²) than other populations; these groups are prone to central adiposity and their cardiometabolic risk occurs at a lower BMI.[117]

Compared with sleeve gastrectomy, Roux en Y leads to somewhat greater weight loss and other benefits, but is a more technically challenging operation with higher re-operation and readmission rates.

chronic heart failure or established atherosclerotic cardiovascular disease or high risk of cardiovascular disease

1st line – metformin

Back

1st line –

metformin

Give metformin as first-line drug treatment to all adults with type 2 diabetes.[36]

For further details about the clinical properties of metformin, see Clinical properties of specific antihyperglycaemic agents in the Management approach.

Primary options

metformin: 500 mg orally (immediate-release) once daily for at least one week, followed by 500 mg twice daily for at least one week, then 500 mg three times daily thereafter, maximum 2000 mg/day

Plus – lifestyle measures and cardiovascular risk reduction

Back

Plus –

lifestyle measures and cardiovascular risk reduction

Treatment recommended for ALL patients in selected patient group

Management of type 2 diabetes needs to be individualised, taking into account the particular requirements and circumstances of the patient, particularly in the context of multimorbidity.[36]

Care of adults with type 2 diabetes must include prompt management of all major cardiovascular risk factors to individualised targets. In addition to glucose control, this includes smoking cessation, blood pressure control, lipid control, consideration of antiplatelet use for patients with high cardiovascular disease risk, and steps to reduce progression of diabetes-related kidney disease.[36][80][107] If the patient smokes, give advice on smoking cessation and information on accessing smoking cessation services.[36][130] The ESC recommends pharmacological therapies (e.g., nicotine replacement therapy, varenicline, bupropion) should be considered, as well as counselling, to improve cessation success rate.[80]

For more detail on lifestyle measures, cardiovascular risk reduction, and pharmacological considerations for people with CKD, see the Initial timeframe.

Consider – sodium-glucose cotransporter-2 (SGLT2) inhibitor

Back

Consider –

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Additional treatment recommended for SOME patients in selected patient group

If the patient is at high risk of developing CVD, as soon as metformin tolerability is confirmed (after gradually increasing the dose of immediate-release metformin over several weeks) consider an SGLT2 inhibitor with proven cardiovascular benefit (e.g., canagliflozin, dapagliflozin, empagliflozin) in addition to metformin.[36]

If the patient has chronic heart failure or established atherosclerotic CVD, add an SGLT2 inhibitor with proven cardiovascular benefit to their treatment regimen, i.e., alongside metformin.[36]

Recommendations to consider/add an SGLT2 inhibitor to metformin in patients at risk of/with CVD are part of a shift in global pharmacotherapy strategies to focus on the improvement of cardiovascular and kidney disease outcomes as well as glycaemic control in type 2 diabetes. These recommendations are based on evidence from a wealth of high-quality, randomised trials which demonstrate that SGLT2 inhibitors have benefits in patients with type 2 diabetes who have multiple risk factors for CVD, and in those with established CVD and/or renal disease. Further details of this evidence can be found in Management approach.

These recommendations apply at all stages of treatment. Therefore, if a patient who did not originally have CVD develops CVD, add an SGLT2 inhibitor with proven cardiovascular benefit in addition to metformin.[36] Likewise, if a patient is newly found to be at high risk of CVD, consider adding an SGLT2 inhibitor to metformin.[36]

Before starting treatment with an SGLT2 inhibitor, always check whether the patient is at an increased risk of diabetic ketoacidosis (DKA), for example if they have had a previous episode of DKA, they are unwell with intercurrent illness, or the patient is following a very low carbohydrate or ketogenic diet.[36] In addition, before starting treatment with an SGLT2 inhibitor, advise the patient of the risk of DKA and address modifiable risk factors for DKA, for example, those who are following a very low carbohydrate or ketogenic diet may need to delay treatment until they have changed their diet.[34][36]

SGLT-2 inhibitors are associated with an increased risk of mycotic genital infections (usually mild and treatable), and an increased risk of diabetic ketoacidosis (although the incidence is low).[73][102][192][193][194][195] The US Food and Drug Administration (FDA) has issued a warning of the risk of acute kidney injury with canagliflozin and dapagliflozin.[196] The Medicines and Healthcare products Regulatory Agency (MHRA) and European Medicines Agency (EMA) warn of an increased risk of lower-limb amputation (mainly toes) in patients with type 2 diabetes taking canagliflozin, and the MHRA emphasises the importance of preventive foot care for all patients with diabetes.[197][198] Therefore, patients with foot ulcers or at high risk for amputation should be given comprehensive foot-care education while treating with SGLT2 inhibitors. The EASD/ADA guidelines on the management of hyperglycaemia in type 2 diabetes notes that while early studies highlighted potential SGLT2 inhibitor-related safety concerns, including acute kidney injury and amputation, longer-term studies that have prospectively assessed and monitored these events have not seen a significant imbalance in risks.[102][199] The MHRA and FDA also warn of cases of necrotising fasciitis of the perineum (also known as Fournier's gangrene) observed in post-marketing surveillance of SGLT2 inhibitors.[200][201]

For further details about the clinical properties of SGLT2 inhibitors, see Clinical properties of specific antihyperglycaemic agents in the Management approach.

Primary options

canagliflozin: 100 mg orally once daily initially, adjust dose according to response, maximum 300 mg/day

dapagliflozin: 10 mg orally once daily

empagliflozin: 10 mg orally once daily initially, adjust dose according to response, maximum 25 mg/day

Consider – bariatric surgery

Back

Consider –

bariatric surgery

Additional treatment recommended for SOME patients in selected patient group

Guidelines from NICE recommend offering an expedited assessment for bariatric surgery to anyone with a BMI of 35 or over who has recent-onset type 2 diabetes (diagnosis within last 10 years) as long as they are also receiving, or will receive, assessment by a specialist weight-management team (a ‘tier 3’ service in the UK).[117] NICE also recommends considering an assessment for bariatric surgery for anyone with a BMI of 30 to 34.9 kg/m² who has recent-onset type 2 diabetes as long as they are also receiving, or will receive, assessment in a ‘tier 3’ service (or equivalent).[117] In addition, an assessment for bariatric surgery should be considered for anyone of South Asian, Chinese, other Asian, Middle Eastern, black African, or African-Caribbean family background, who has recent-onset type 2 diabetes using a lower BMI threshold (reduced by 2.5 kg/m²) than other populations as long as they are also receiving, or will receive, assessment in a ‘tier 3’ service (or equivalent); these groups are prone to central adiposity and their cardiometabolic risks occur at lower BMIs.[117]

Compared with sleeve gastrectomy, Roux en Y leads to somewhat greater weight loss and other benefits, but is a more technically challenging operation with higher re-operation and readmission rates.

2nd line – sodium-glucose cotransporter-2 (SGLT2) inhibitor

Back

2nd line –

sodium-glucose cotransporter-2 (SGLT2) inhibitor

If metformin is contraindicated or not tolerated, alternative drug therapy should be based on the patient’s cardiovascular risk profile.[36]

If the patient is at high risk of developing cardiovascular disease (aged ≥40 years with QRISK3 ≥10%, or aged <40 years with ≥1 cardiovascular risk factors), consider an SGLT2 inhibitor with proven cardiovascular benefit (e.g., canagliflozin, dapagliflozin, empagliflozin) in place of metformin.[36]

If the patient has chronic heart failure or established atherosclerotic CVD, give an SGLT2 inhibitor with proven cardiovascular benefit instead of metformin.[36]

For further details about the clinical properties of SGLT2 inhibitors, see Clinical properties of specific antihyperglycaemic agents in the Management approach.

Primary options

canagliflozin: 100 mg orally once daily initially, adjust dose according to response, maximum 300 mg/day

dapagliflozin: 10 mg orally once daily

empagliflozin: 10 mg orally once daily initially, adjust dose according to response, maximum 25 mg/day

Plus – lifestyle measures and cardiovascular risk reduction

Back

Plus –

lifestyle measures and cardiovascular risk reduction

Treatment recommended for ALL patients in selected patient group

Management of type 2 diabetes needs to be individualised, taking into account the particular requirements and circumstances of the patient, particularly in the context of multimorbidity.[36]

Care of adults with type 2 diabetes must include prompt management of all major cardiovascular risk factors to individualised targets. In addition to glucose control, this includes smoking cessation, blood pressure control, lipid control, consideration of antiplatelet use for patients with high cardiovascular disease risk, and steps to reduce progression of diabetes-related kidney disease.[36][80][107] If the patient smokes, give advice on smoking cessation and information on accessing smoking cessation services.[36][130] The ESC recommends pharmacological therapies (e.g., nicotine replacement therapy, varenicline, bupropion) should be considered, as well as counselling, to improve cessation success rate.[80]

For more detail on lifestyle measures, cardiovascular risk reduction, and pharmacological considerations for people with CKD, see the Initial timeframe.

Consider – bariatric surgery

Back

Consider –

bariatric surgery

Additional treatment recommended for SOME patients in selected patient group

Guidelines from NICE recommend offering an expedited assessment for bariatric surgery to anyone with a BMI of 35 kg/m² or over who has recent-onset type 2 diabetes (diagnosis within last 10 years) as long as they are also receiving, or will receive, assessment by a specialist weight-management team.[117] NICE also recommends considering an expedited assessment for bariatric surgery for anyone with a BMI of 30 to 34.9 kg/m² who has recent-onset type 2 diabetes as long as they are also receiving, or will receive, assessment in a sepcialist weight-management team.[117] In addition, an expedited assessment for bariatric surgery should be considered for anyone of South Asian, Chinese, other Asian, Middle Eastern, black African, or African-Caribbean family background, who has recent-onset type 2 diabetes using a lower BMI threshold (reduced by 2.5 kg/m²) than other populations; these groups are prone to central adiposity and their cardiometabolic risk occurs at a lower BMI.[117]

Compared with sleeve gastrectomy, Roux en Y leads to somewhat greater weight loss and other benefits, but is a more technically challenging operation with higher re-operation and readmission rates.

HbA1C above agreed threshold on initial pharmacotherapy or cardiovascular risk changes: non-pregnant

1st line – switch or add treatments

Back

1st line –

switch or add treatments

If the patient’s HbA1c is not controlled to below their individually agreed threshold with initial treatment, consider how to optimise their current treatment regimen before thinking about changing treatments, taking into account factors such as adverse effects and adherence to existing medication.[36] Thereafter, switching or adding treatments may be appropriate.

Specifically, if initial therapy has not continued to control HbA1c to below the person's individually agreed threshold for further intervention, consider switching to, or adding a dipeptidyl peptidase-4 (DPP-4) inhibitor, pioglitazone, a sulfonylurea, or a sodium-glucose cotransporter-2 (SGLT2) inhibitor.[36][153][154][155][156] (Specific details of treatment types and doses, along with adverse events, can be found in the ‘HbA1C above goal: non-pregnant patient group.)

If dual therapy with metformin and another oral drug has not continued to control HbA1c to below the patient’s individually agreed threshold for further intervention, consider either: triple therapy by adding a DPP-4 inhibitor, pioglitazone, a sulfonylurea, or an SGLT2-inhibitor; or starting insulin-based treatment.[36][154][155][157][158]

If metformin is contraindicated or not tolerated and dual therapy with 2 oral drugs has not continued to control HbA1c to below the patient's individually agreed threshold for intervention, consider insulin-based treatment.[36]

If triple therapy with metformin and 2 other oral agents is not effective, not tolerated, or contraindicated, NICE recommends considering triple therapy by switching one drug for a glucagon-like peptide (GLP-1) receptor agonist in certain patients.[36] In 2023, NICE recommended tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, for adults with type 2 diabetes, as an alternative to GLP-1 receptor agonists (i.e., tirzepatide is an option to be considered at the same level of the UK type 2 diabetes treatment pathway, and to be used within the same criteria, as for GLP-1 receptor agonists).[159]

Drugs should be introduced in a stepwise manner, checking for tolerability and effectiveness of each drug.[36]

Choice of agents should be individualised, taking into account patient preferences, needs and clinical circumstances (e.g. weight, comorbidities such as chronic kidney disease, risks of complications), the effectiveness of the agent in terms of metabolic response and cardiovascular and renal protection, adverse effects, and other factors.[36][80][102] Consider and discuss with the patient stopping medicines that are not tolerated or have had no impact on glycaemic control or weight (unless there is an additional clinical benefit).[36]

Give careful consideration to the drug combinations, ensuring that they are safe and appropriate for your patient. If possible, avoid combining insulin with pioglitazone. The UK Medicines and Healthcare products Regulatory Agency (MHRA) warns that patients should be observed for signs and symptoms of heart failure, weight gain, and oedema if pioglitazone is used in combination with insulin. This is owing to the increased incidence of cardiac failure when pioglitazone is used in combination with insulin, especially in patients with predisposing factors.[160]

Only offer a GLP-1 receptor agonist in combination with insulin with specialist care advice and ongoing support from a consultant-led multi-disciplinary team.[36] The MHRA warns of cases of diabetic ketoacidosis in patients with type 2 diabetes on a combination of a GLP-1 receptor agonist and insulin, who had doses of concomitant insulin rapidly reduced or discontinued.[161] The MHRA warns that the same risk cannot be excluded for the dual GIP/GLP-1 receptor agonist, tirzepatide, and appropriate caution should be taken if this is being used in combination with insulin.

Bear in mind that recommendations for drugs with cardiovascular and renal benefit apply at all stages of treatment. Therefore, if a patient who did not originally have CVD develops CVD, add an SGLT2 inhibitor with proven cardiovascular benefit to their existing treatment regimen or give an SGLT2 inhibitor in place of an existing drug.[36] Likewise, if a patient is newly found to be at high risk of CVD, consider adding an SGLT2 inhibitor to their current treatments, or to switch one of their current drugs to an SGLT2 inhibitor.[36]

The most appropriate drug regimens for a frail patient, including choice of drug and optimal dose, will need careful consideration and are likely to differ from those recommended for younger, fit patients.[83] 'Start low and go slow' when dosing and titrating medications in frail older adults.[83] Balance the intended benefit of treatment against the risk of adverse treatment effects.[108] De-escalation of therapy is as important as intensification in this population. The ADA recommends use of medicines with low hypoglycaemia risk for older adults, and deintensification and/or simplification of treatment plans (within individualised glycaemic goals) in this population when the harms or burdens of treatment may outweigh the benefits.[34]

When choosing, reviewing, and changing medicines, always reinforce advice about diet and lifestyle.[36]

Plus – lifestyle measures and cardiovascular risk reduction

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Plus –

lifestyle measures and cardiovascular risk reduction

Treatment recommended for ALL patients in selected patient group

Management of type 2 diabetes needs to be individualised, taking into account the particular requirements and circumstances of the patient, particularly in the context of multimorbidity.[36]

Care of adults with type 2 diabetes must include prompt management of all major cardiovascular risk factors to individualised targets. In addition to glucose control, this includes smoking cessation, blood pressure control, lipid control, consideration of antiplatelet use for patients with high cardiovascular disease risk, and steps to reduce progression of diabetes-related kidney disease.[36][80][107] If the patient smokes, give advice on smoking cessation and information on accessing smoking cessation services.[36][130] The ESC recommends pharmacological therapies (e.g., nicotine replacement therapy, varenicline, bupropion) should be considered, as well as counselling, to improve cessation success rate.[80]

For more detail on lifestyle measures, cardiovascular risk reduction, and pharmacological considerations for people with CKD, see the Initial timeframe.

Consider – insulin

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Consider –

insulin

Additional treatment recommended for SOME patients in selected patient group

Insulin can be given in isolation or with other glucose lowering medicines.[36]

Consider starting insulin-based treatment if dual therapy with metformin and another oral drug has not continued to control HbA1c to below the patient’s individually agreed threshold for further intervention, or if metformin is contraindicated or not tolerated and dual therapy with 2 oral drugs has not continued to control HbA1c to below the patient's individually agreed threshold for intervention.[36]

When starting insulin therapy, the patient should continue metformin as long as there are no contraindications or intolerances.[36] Review the continued need for other blood glucose-lowering therapies (e.g., consider additive hypoglycaemia risk and if there are additional benefits of continuing other drugs, such as cardiometabolic or kidney-related).[34][36]

Choose the most appropriate insulin type for the patient, and develop an individualised regimen.[36]

Give basal isophane (neutral protamine Hagedorn, NPH) insulin injected once or twice daily according to need; consider starting both NPH and short-acting insulin (particularly if the person's HbA1c is 75 mmol/mol [9.0%] or higher), administered either separately, or as a pre-mixed (biphasic) human insulin preparation.[36]

Consider using insulin detemir or insulin glargine as an alternative to NPH insulin if the patient needs assistance from a carer or healthcare professional to inject insulin, and use of insulin detemir or insulin glargine would reduce the frequency of injections from twice to once daily; or if the patient’s lifestyle is restricted by recurrent symptomatic hypoglycaemic episodes; or if the patient would otherwise need twice-daily NPH insulin injections in combination with oral glucose-lowering drugs.[36]

Consider pre-mixed (biphasic) preparations that include short-acting insulin analogues, rather than pre-mixed (biphasic) preparations that include short-acting human insulin preparations, if: the patient prefers injecting insulin immediately before a meal, or hypoglycaemia is a problem, or blood glucose levels rise markedly after meals.[36]

Consider switching to insulin detemir or insulin glargine from NPH insulin if the patient: does not reach their target HbA1c because of significant hypoglycaemia; or experiences significant hypoglycaemia on NPH insulin irrespective of the level of HbA1c reached; or cannot use the device needed to inject NPH insulin but could administer their own insulin safely and accurately if switched to one of the long-acting insulin analogues; or needs help from a carer or healthcare professional to administer insulin injections and for whom switching to one of the long-acting insulin analogues would reduce the number of daily injections.[36]

If the patient is on a basal insulin regimen (NPH insulin, insulin detemir, or insulin glargine), monitor for the need for short-acting insulin before meals (or a pre-mixed [biphasic] insulin preparation).[36]

If the patient is on pre-mixed (biphasic) insulin, monitor for the need for a further injection of short-acting insulin before meals or for a change to a basal-bolus regimen with NPH insulin or insulin detemir or insulin glargine, if blood glucose control remains inadequate.[36]

When basal-bolus insulin is used by motivated and knowledgeable patients, the dose of rapid-acting insulin that is administered before each meal can be based on anticipated carbohydrate content of the upcoming meal and sometimes adjusted for anticipated physical activity.

A correction (or adjustment) dose may be added to the bolus insulin based on the pre-meal blood glucose level. In practice, a conservative approach to calculating a correction dose is to assume 1 unit of insulin will lower the patient’s blood glucose by 2-4 mmol/L (36-72 mg/dL). Correction dosing can also be calculated using the patient's total daily dose of insulin if food intake is stable. The correction dose can be added to the patient's mealtime insulin requirement (whether based on general meal size or carbohydrate counting) and given as the total bolus dose.

Most people with type 2 diabetes will use insulin delivery devices (insulin pens). These can be adjusted to administer set doses of insulin, are widely available, and offer convenience and accuracy in insulin dosing. Less frequently, insulin pumps and patch pump systems are used on a case-by-case basis in people who need multiple daily dose insulin. Insulin pumps are typically reserved for people with type 1 diabetes. If an insulin pump is appropriate for the patient, its use will require significant patient engagement to achieve clinical benefits beyond multiple daily dose injection-based therapy.

Exogenous insulin is a very effective way to lower serum glucose and lower HbA1c, but its use must be guided in most patients by regular self-monitored blood glucose testing (finger stick blood glucose testing) or continuous glucose monitoring. Hypoglycaemia (glucose ≤3.9 mmol/L [≤70 mg/dL]) is the most serious potential complication of insulin therapy. People who drive need to be particularly careful to avoid hypoglycaemia and should be warned of the dangers. See the Complication section of this topic. Another significant adverse effect is weight gain. Less common adverse effects may include hunger, nausea, diaphoresis, injection site irritation, or anaphylaxis.

Give careful consideration to the drug combinations used with insulin, ensuring that they are safe and appropriate for your patient. If possible, avoid combining insulin with pioglitazone. The UK Medicines and Healthcare products Regulatory Agency (MHRA) warns that patients should be observed for signs and symptoms of heart failure, weight gain, and oedema if pioglitazone is used in combination with insulin. This is owing to the increased incidence of cardiac failure when pioglitazone is used in combination with insulin, especially in patients with predisposing factors.[160]

Only offer a glucagon-like peptide (GLP-1) receptor agonist in combination with insulin with specialist care advice and ongoing support from a consultant-led multi-disciplinary team.[36] The MHRA warns of cases of diabetic ketoacidosis in patients with type 2 diabetes on a combination of a GLP-1 receptor agonist and insulin, who had doses of concomitant insulin rapidly reduced or discontinued.[161] The MHRA warns that the same risk cannot be excluded for the dual GIP/GLP-1 receptor agonist, tirzepatide, and appropriate caution should be taken if this is being used in combination with insulin.

Various pre-mixed (biphasic) insulin formulations are available; consult your local drug formulary for options.

Primary options

insulin isophane human (NPH)

insulin detemir

insulin glargine

insulin isophane human (NPH)

insulin detemir

insulin glargine

-- AND --

insulin lispro

insulin aspart

insulin glulisine

Consider – glucagon-like peptide (GLP-1) receptor agonist or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist

Back

Consider –

glucagon-like peptide (GLP-1) receptor agonist or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist

Additional treatment recommended for SOME patients in selected patient group

If triple therapy with metformin and 2 other oral agents is not effective, not tolerated, or contraindicated, NICE recommends considering triple therapy by switching one drug for a GLP-1 receptor agonist in patients who have a BMI ≥35 kg/m² (adjust accordingly for people from black, Asian, and other minority ethnic groups) and specific psychological or other medical problems associated with obesity; or in patients with a BMI <35 kg/m² and for whom insulin therapy would have significant occupational implications, or for whom weight loss would benefit other significant obesity-related comorbidities.[36] In 2023, NICE recommended tirzepatide (a dual GIP/GLP-1 receptor agonist) for adults with type 2 diabetes, as an alternative to GLP-1 receptor agonists (i.e., tirzepatide is an option to be considered at the same level of the UK type 2 diabetes treatment pathway, and to be used within the same criteria, as for GLP-1 receptor agonists).[159]

While NICE recommends consideration of a basal-bolus insulin regimen for patients who are unable to maintain glycaemic targets on basal insulin alone, the ADA/EASD also notes an alternative option of adding a GLP-1 receptor agonist to basal insulin to intensify treatment.[102] Further, the ADA 2024 diabetes guidelines include that, if insulin is used in an adult with type 2 diabetes, it is recommended to use it in combination with a GLP-1 receptor agonist or a dual GIP/GLP-1 receptor agonist for greater glycaemic efficacy (and added weight and hypoglycaemia risk benefits), with the insulin dose adjusted as needed when one of these agents is added or uptitrated.[34] Trial data support the combination of basal insulin and a GLP-1 receptor agonist to lower HbA1c and limit weight gain and hypoglycaemia when compared with an intensified insulin regimen.[236][237][238] This could be particularly useful for patients with obesity who will require high doses of insulin because of insulin resistance, making the adverse effect of weight gain from insulin use especially problematic. However, only offer a GLP-1 receptor agonist in combination with insulin with specialist care advice and ongoing support from a consultant-led multi-disciplinary team.[36]

KDIGO notes that if additional glycaemic management is required in patients with type 2 diabetes and CKD following first-line treatment with metformin and SGLT2 inhibitors, GLP-1 receptor agonists are generally preferred.[135] Similarly, the ESC recommends the use of a GLP-1 receptor agonist for additional glucose control (if required) in those with CKD and eGFR >15 mL/min/1.73 m² (given that these agents carry a low risk of hypoglycaemia and have beneficial effects on weight, cardiovascular risk, and albuminuria).[80]

Although NICE does not recommend GLP-1 receptor agonists as first-line treatment for type 2 diabetes, the ADA/EASD recommends that monotherapy with a GLP-1 receptor agonist (e.g., dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or an SGLT2 inhibitor can be considered as an alternative to metformin, based on evidence regarding the cardiovascular and renal benefits of these drug classes, independent of their glucose-lowering effects.[102][146] The ESC also recommends (independent of baseline or target HbA1c and any concomitant glucose-lowering medicine) GLP-1 receptor agonists and SGLT2 inhibitors, with proven cardiovascular benefits, for patients with type 2 diabetes with established ASCVD, to reduce CV events.[80] They further advise these same agents may be considered (as well as considering metformin) for patients with type 2 diabetes without ASCVD or severe TOD but with a 10-year CVD risk ≥10%, to reduce cardiovascular risk.[80] They advise that treatment with metformin should not be a pre-requisite to use of GLP-1 receptor agonists or SGLT2 inhibitors for cardiovascular benefit.[80] See Management approach for more details.

The most common adverse effects of GLP-1 inhibitors are gastrointestinal, such as nausea, vomiting, and diarrhoea, but they tend to reduce over time. In addition, the MHRA warns of cases of diabetic ketoacidosis in patients with type 2 diabetes on a combination of a GLP-1 receptor agonist and insulin who had doses of concomitant insulin rapidly reduced or discontinued.[161] Pancreatitis has been reported in clinical trials of GLP-1 receptor agonists, but the causality has not been established.[102] There is conflicting evidence regarding whether GLP-1 receptor agonists increase the risk of thyroid disorders. A 2022 meta-analysis of randomised-controlled trials concluded that GLP-1 receptor agonists did not increase or decrease the risk of thyroid cancer, hyperthyroidism, hypothyroidism, thyroiditis, thyroid mass, and goiter, although it noted that due to the low incidence of these diseases, these findings needed to be examined further.[213] However, a nested case-control analysis of 2562 subjects with thyroid cancer reported that GLP-1 receptor agonist use was associated with an increased risk all thyroid cancer and medullary thyroid cancer, in particular after 1-3 years of treatment.[214] A systematic review and network meta-analysis combining 84 trials investigating the effect of GLP-1 receptor agonists and DPP-4 inhibitors (incretin-based therapies) concluded that they were not associated with an increased risk of cancers of the digestive system in patients with type 2 diabetes.[215] The European Medicines Agency is reviewing data on the risk of suicidal thoughts and thoughts of self-harm with GLP-1 receptor agonists, following reports of such occurrences in people using liraglutide and semaglutide.

Tirzepatide was reasonably well tolerated in trials, with the most common adverse effects being similar to those seen with GLP-1 receptor agonists (nausea, vomiting, and dyspepsia). Slow uptitration of the dose of tirzepatide may minimise the risk of these adverse effects.[159] The same warnings and cautions for GLP-1 receptor agonists apply to tirzepatide.

For further details about the clinical properties of GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists, see Clinical properties of specific antihyperglycaemic agents in the Management approach.

Primary options

dulaglutide: 1.5 mg subcutaneously once weekly initially for at least 4 weeks, adjust dose according to response, maximum 4.5 mg/week

exenatide: 5 micrograms subcutaneously (immediate-release) twice daily initially for at least 1 month, adjust dose according to response, maximum 20 micrograms/day; 2 mg subcutaneously (modified-release) once weekly

liraglutide: 0.6 mg subcutaneously once daily initially for at least 1 week, adjust dose according to response, maximum 1.8 mg/day

lixisenatide: 10 micrograms subcutaneously once daily initially for 2 weeks, adjust dose according to response, maximum 20 micrograms/day

semaglutide: 0.25 mg subcutaneously once weekly initially for 4 weeks, adjust dose according to response, maximum 2 mg/week; 3 mg orally once daily initially for 1 month, adjust dose according to response, maximum 14 mg/day

tirzepatide: 2.5 mg subcutaneously once weekly initially for 4 weeks, adjust dose according to response, maximum 15 mg/dose

Consider – bariatric surgery

Back

Consider –

bariatric surgery

Additional treatment recommended for SOME patients in selected patient group

Guidelines from NICE recommend offering an expedited assessment for bariatric surgery to anyone with a BMI of 35 kg/m² or over who has recent-onset type 2 diabetes (diagnosis within last 10 years) as long as they are also receiving, or will receive, assessment by a specialist weight-management team.[117] NICE also recommends considering an expedited assessment for bariatric surgery for anyone with a BMI of 30 to 34.9 kg/m² who has recent-onset type 2 diabetes as long as they are also receiving, or will receive, assessment in a specialist weight-management team.[117] In addition, an expedited assessment for bariatric surgery should be considered for anyone of South Asian, Chinese, other Asian, Middle Eastern, black African, or African-Caribbean family background, who has recent-onset type 2 diabetes using a lower BMI threshold (reduced by 2.5 kg/m²) than other populations; these groups are prone to central adiposity and their cardiometabolic risk occurs at a lower BMI.[117]

Compared with sleeve gastrectomy, Roux en Y leads to somewhat greater weight loss and other benefits, but is a more technically challenging operation with higher re-operation and readmission rates.

pregnant

1st line – low-dose aspirin

Back

1st line –

low-dose aspirin

Advise pregnant women with type 2 diabetes to take low-dose aspirin from 12 weeks until the birth of the baby.[99][258] These women are at high-risk of pre-eclampsia.[258]

Primary options

aspirin: 75-150 mg orally once daily

Consider – metformin

Back

Consider –

metformin

Additional treatment recommended for SOME patients in selected patient group

Women with diabetes may be advised to use metformin with or without insulin during pregnancy (and in the preconception period), when the likely benefits from improved blood glucose control outweigh the potential for harm.[99]

Stop all other oral blood glucose-lowering agents before and throughout pregnancy.[99] Women who are breastfeeding can resume or continue metformin immediately after birth, but should avoid other oral blood glucose-lowering therapy while breastfeeding.[99]

For further details about the clinical properties of metformin, see Clinical properties of specific antihyperglycaemic agents in the Management approach.

Primary options

metformin: 500 mg orally (immediate-release) once daily for at least one week, followed by 500 mg twice daily for at least one week, then 500 mg three times daily thereafter, maximum 2000 mg/day

Consider – insulin

Back

Consider –

insulin

Additional treatment recommended for SOME patients in selected patient group

The National Institute for Health and Care Excellence in the UK recommends isophane (NPH) insulin as the first choice for long-acting insulin during pregnancy.[99] Consider continuing treatment with long-acting insulin analogues (insulin detemir or insulin glargine) for women with diabetes who have established good blood glucose control while using these before pregnancy.[99]

The available evidence on rapid-acting insulin analogues (insulin aspart and insulin lispro) does not show an adverse effect on pregnancy or the health of the baby.[99]

Advise pregnant women with diabetes who are on insulin to maintain their capillary plasma glucose level above 4 mmol/L (72 mg/dL).[99]

In practice, the majority of pregnant women with type 2 diabetes will need insulin.

Primary options

insulin isophane human (NPH)

insulin detemir

insulin glargine

-- AND --

insulin lispro

insulin aspart

Plus – lifestyle measures and review medication

Back

Plus –

lifestyle measures and review medication

Treatment recommended for ALL patients in selected patient group

As well as lifestyle advice for non-pregnant people with type 2 diabetes (see the Initial timeframe), give specific advice to patients who are planning pregnancy or are pregnant.

Women with type 2 diabetes should use an effective method of contraception until they plan pregnancy.[99] Women should be evaluated before pregnancy for retinopathy, nephropathy, neuropathy, and possible cardiovascular disease, which may worsen during or complicate pregnancy.[99]

Explain to women with diabetes who are planning pregnancy that if they have good blood glucose control before conception and throughout their pregnancy, this will reduce the risk of miscarriage, congenital malformation, stillbirth, and neonatal death. Also explain that the risks can be reduced but not eliminated.[99]

Agree individualised targets for self-monitoring of blood glucose with women who have diabetes and are planning a pregnancy, taking into account the risk of hypoglycaemia.[99]

The National Institute for Health and Care Excellence (NICE) in the UK recommends that HbA1c should be <48 mmol/mol (6.5%) before conception if this can be achieved without problematic hypoglycaemia.[99] Any reduction towards this target is likely to reduce the risk of congenital malformations. NICE recommends up to monthly measurement of HbA1c levels for women with diabetes who are planning a pregnancy.[99] Strongly advise women with diabetes whose HbA1c level is above 86 mmol/mol (10%) not to get pregnant until their HbA1c level is lower, because of the associated risks.[99]

Review the patient’s medication. Stop any drugs contraindicated in pregnancy if your patient is planning pregnancy or as soon as pregnancy is confirmed; use alternative agents that are suitable for pregnant women. Women with diabetes may be advised to use metformin (with or without insulin) in the preconception period (and during pregnancy), when the likely benefits from improved blood glucose control outweigh the potential for harm (see section on metformin in pregnant patients). Stop all other oral blood glucose-lowering agents before (and throughout) pregnancy, including SGLT2 inhibitors.[99][136]

Stop ACE inhibitors and angiotensin-II receptor antagonists before conception, or as soon as pregnancy is confirmed.[99] Stop statins before pregnancy, or as soon as pregnancy is confirmed.[99] Women with diabetes who are breastfeeding can resume or continue metformin immediately after birth, but should avoid other oral blood glucose-lowering therapy while breastfeeding and continue to avoid any medicines for their diabetes complications that were stopped for safety reasons when they started planning the pregnancy.[99]

Advise women who are planning a pregnancy to take folic acid (5 mg/day), which should be continued until 12 weeks of gestation.[99] Women with diabetes have an increased risk of having infants with neural tube defects, compared with the general population.[257]

Diet and lifestyle are central to this management of type 2 diabetes. Offer structured education to the patient (and/or their family members or carers) at and around the time of diagnosis, with annual reinforcement and review.[36] Ongoing self-management education by a diabetes education nurse or dietitian promotes diabetes self-care and supports beneficial lifestyle changes.[36][103][104][105] This requires general nutrition and health lifestyle knowledge and an individualised nutrition and exercise plan based on an initial assessment and treatment goals. Interventions that enhance self-management can significantly reduce diabetes distress.[106]

During pregnancy, women should be cared for by a multi-disciplinary team, including a dietitian, a nurse educator, an endocrinologist, and an obstetrician.

Offer pregnant women with pre-existing diabetes retinal assessment by digital imaging with mydriasis using tropicamide following their first antenatal clinic appointment (unless they have had a retinal assessment in the last 3 months), and again at 28 weeks. If any diabetic retinopathy is present at booking, perform an additional retinal assessment at 16-20 weeks.[99]

NICE guidelines recommend the following blood glucose targets in pregnant women with pre-existing type 2 diabetes (as long as these are achievable without causing problematic hypoglycaemia): fasting: <5.3 mmol/L (<95.4 mg/dL); 1 hour after meals: <7.8 mmol/L (<140.4 mg/dL); 2 hours after meals: <6.4 mmol/L (<115.2 mg/dL).[99][Evidence C]

Measure HbA1c levels in all pregnant women with pre-existing diabetes at the booking appointment to determine the level of risk for the pregnancy. Consider measuring HbA1c levels in the second and third trimesters of pregnancy for women with pre-existing diabetes to assess the level of risk for the pregnancy.[99] Good glucose control with HbA1c as close to normal as is safely possible (ideally HbA1c <48 mmol/mol [<6.5%]) before conception and during pregnancy optimises maternal and fetal health outcomes.[99]

Pregnant women should test their fasting, pre-meal, 1-hour post-meal, and bedtime blood glucose levels every day.[34][99] The pattern should be examined every few weeks early in pregnancy so that nutrition content and timing, exercise patterns, and the insulin doses can be modified to achieve optimal control. CGM monitoring during pregnancy may be considered on an individual basis (in addition to self-monitoring) for those taking insulin who are experiencing problematic severe hypoglycaemia or who have unstable blood glucose levels causing concern despite efforts to optimise control.[34][99] Insulin requirements generally increase early in pregnancy, then decrease from about 8-16 weeks before rising throughout the rest of the pregnancy.

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Type 2 diabetes in adults

Treatment algorithm

at initial diagnosis

lifestyle changes

agree glycaemic (HbA1c) target

blood pressure management

lipid management

antiplatelet therapy

add-on pharmacotherapy for patients with CKD

insulin or sulfonylurea

HbA1C above goal: non-pregnant

metformin

Primary options

lifestyle measures and cardiovascular risk reduction

bariatric surgery

dipeptidyl peptidase-4 (DPP-4) inhibitor or pioglitazone or sulfonylurea or sodium-glucose cotransporter-2 (SGLT2) inhibitor

Primary options

DPP-4 inhibitor

DPP-4 inhibitor

DPP-4 inhibitor

DPP-4 inhibitor

DPP-4 inhibitor

Thiazolidinedione

Sulfonylurea

Sulfonylurea

SGLT2 inhibitor

SGLT2 inhibitor

SGLT2 inhibitor

SGLT2 inhibitor

lifestyle measures and cardiovascular risk reduction

bariatric surgery

metformin

Primary options

lifestyle measures and cardiovascular risk reduction

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Primary options

bariatric surgery

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Primary options

lifestyle measures and cardiovascular risk reduction

bariatric surgery

HbA1C above agreed threshold on initial pharmacotherapy or cardiovascular risk changes: non-pregnant

switch or add treatments

lifestyle measures and cardiovascular risk reduction

insulin

Primary options

glucagon-like peptide (GLP-1) receptor agonist or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist

Primary options

bariatric surgery

pregnant

low-dose aspirin

Primary options

metformin

Primary options

insulin

Primary options

lifestyle measures and review medication

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