Type 2 diabetes in children

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

ACUTE

ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome

1st line – intravenous insulin + hydration

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1st line –

intravenous insulin + hydration

Ketoacidosis may be present in 5% to 25% of children with type 2 diabetes at presentation.[64] Stressful events such as illness, trauma, and surgery may also cause a decline in glycemic control and precipitate ketoacidosis.[1]

Hyperosmolar hyperglycemic nonketotic syndrome (HHNS) may form part of the initial presentation of type 2 diabetes in up to 2% of children.[64] Stressful events such as illness, trauma, and surgery may also cause a decline in glycemic control and precipitate HHNS.[1] Children and adolescents presenting with severe hyperglycemia (blood glucose ≥600 mg/dL [≥33.3 mmol/L]) should be assessed for HHNS.[1]

Any child who presents in ketoacidosis with volume depletion or HHNS should be admitted and placed on intravenous insulin and fluids.[64] Typically used fluids include full-strength (0.9%) or half-strength (0.45%) normal saline, depending on hydration status, serum sodium concentrations, and osmolality.[64] Serum potassium concentrations need to be closely monitored during treatment and replaced as necessary. Deficits in phosphate and magnesium may also need to be addressed.[64] In general, deficits of potassium, phosphate, and magnesium are greater in HHNS than ketoacidosis.[64] Fluid replacement should begin before starting insulin therapy.[64] Differences in treatment strategy between HHNS and ketoacidosis include the volume of fluid administered and the timing of insulin administration: in ketoacidosis the rates of fluid infusion are substantially lower than for HHNS; in ketoacidosis insulin administration can begin at least 1 hour after starting fluid replacement, while in HHNS insulin should be started when blood glucose decreases by <50 mg/dL (3 mmol/L) per hour with fluids alone.[64] Mixed presentation of ketoacidosis and HHNS - where children meet criteria for both ketoacidosis and have hyperosmolality - is frequently unrecognized.[64] In these circumstances, treatment must account for potential complications of both ketoacidosis and HHNS; mental status should be monitored and frequent reassessment of circulatory status and fluid balance is necessary to guide therapy.[64]

See local specialist protocols for insulin dosing guidelines.

Primary options

insulin regular

Plus – switch to subcutaneous insulin

Back

Plus –

switch to subcutaneous insulin

Treatment recommended for ALL patients in selected patient group

Once ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome has resolved, patients should be switched from intravenous insulin to subcutaneous basal-bolus insulin.[1]

Insulin therapy requires that the patient self-monitor blood glucose to avoid hypoglycemia, the most serious complication of insulin treatment, and to allow adjustment of doses to achieve optimal hemoglobin A1c (HbA1c).[1]

An insulin pump may be considered as an alternative to a regimen of multiple daily injections if the patient is able to manage the device safely.[1]

Once fasting and postprandial blood glucose values are restored to normal or near-normal levels (<80-130 mg/dL [<4.4 to 7.2 mmol/mol] fasting and <180 mg/dL [<10.0 mmol/mol] postprandial), it may be appropriate to consider discontinuing insulin therapy for selected patients.

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes. Individuals who are positive for pancreatic autoantibodies should discontinue metformin and continue insulin therapy.[1] See Type 1 diabetes mellitus.

See local specialist protocols for insulin dosing guidelines.

Primary options

insulin glargine

insulin degludec

insulin detemir

insulin NPH

-- AND --

insulin lispro

insulin aspart

insulin glulisine

Plus – metformin

Back

Plus –

metformin

Treatment recommended for ALL patients in selected patient group

Metformin should be initiated once ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome has resolved.[1]

Metformin improves hyperglycemia primarily through its suppression of hepatic glucose production, especially hepatic gluconeogenesis. It also causes anorexia and a modest amount of weight loss.

An extended-release formulation of metformin is available in some countries and can be given once daily. The extended-release formulation is preferred over the immediate-release formulation due to less frequent gastrointestinal adverse effects; however, safety and efficacy of the extended-release preparation has not been established in children. Metformin is also available in a solution for children unable to swallow tablets.

Individuals who are positive for pancreatic autoantibodies should discontinue metformin once results are back.[1] See Type 1 diabetes mellitus.

When choosing glucose-lowering medications for youth with type 2 diabetes and overweight or obesity, consider the effects of medications and medication-taking behavior on their weight.[1]

Primary options

metformin: children <10 years of age: consult specialist for guidance on dose; children ≥10 years of age: 500 mg orally (immediate-release) once daily initially, increase by 500 mg/day increments every 1-2 weeks according to response, maximum 2000 mg/day

ONGOING

HbA1c <8.5%: no acidosis or ketosis

1st line – metformin

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1st line –

metformin

Metformin is the first-line pharmacotherapy for all children diagnosed with type 2 diabetes who are metabolically stable with normal renal function.[1] This recommendation is supported by results from the TODAY study, which showed that metformin monotherapy provided durable glycemic control in approximately 50% of the participating children and adolescents.[77]

Metformin improves hyperglycemia primarily through its suppression of hepatic glucose production, especially hepatic gluconeogenesis. It also causes anorexia and a modest amount of weight loss.

Primary options

Plus – lifestyle modifications

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Plus –

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

All children require dietary modifications, exercise, counseling, and diabetes education.[1] Weight loss with its concomitant decrease in insulin resistance should be the primary goal for every individual.

Referral to an experienced dietitian is highly recommended. Dietary guidance to address children's overconsumption of energy-dense, nutrient-poor foods and beverages, physical activity patterns, the impact of school meals on children's diets, and the roles of parents and caregivers in influencing the development of healthy eating behaviors should be provided to every family.[48] Children with type 2 diabetes with overweight/obesity should aim for at least a 7% to 10% decrease in excess weight.[1] Calories need to be restricted to achieve recommended weight loss. Nutrition advice needs to be tailored to the needs of each individual patient, with an optimal mix of carbohydrate, fats, and protein. Protein intake should not exceed the recommended daily allowance of 0.8 g/kg/day.[1]

Low-carbohydrate diets are popular and theoretically promising for the management of type 2 diabetes in children, but evidence is currently insufficient to support their widespread use, according to the American Academy of Pediatrics’ Committee on Nutrition.[69] Furthermore, carbohydrate restriction has potential risks for children with diabetes, notably growth deceleration, nutritional deficiencies, poor bone health, nutritional ketosis that cannot be distinguished from ketosis resulting from insulin deficiency, and disordered eating behaviors. Rather than focusing purely on carbohydrate restriction, the Committee on Nutrition recommends increasing dietary fiber, reducing consumption of nutrient-poor carbohydrates, particularly processed foods with high amounts of refined grains and added sugars, and eliminating sugar-sweetened beverages.[69] For patients in whom weight loss or maintenance is medically indicated, a reduced-energy diet, irrespective of carbohydrate content, is most important for achieving weight loss. Consider advising a healthy dietary pattern strategy (i.e., Mediterranean diet, Dietary Guidelines for Americans) and striving for 60 minutes per day of moderate to vigorous aerobic activity to reduce obesity, improve diabetes-related health outcomes, and promote optimal glycemic and cardiometabolic outcomes. Regular medical follow-up is recommended for patients with diabetes who do choose to follow a low-carbohydrate diet.[69]

At least 60 minutes of moderate to vigorous aerobic exercise daily, and strength training on at least 3 days per week should be implemented to help improve glycemic control, assist with weight maintenance, and reduce comorbidities (e.g., cardiovascular risk).[1][71][72][73][74][75]

A smoking history should be taken at initial and follow-up appointments. All children and adolescents should be advised not to smoke, including electronic cigarettes, or encouraged to quit if they already smoke.[1] Smoking cessation counseling should be included as a routine component of diabetes care.

pancreatic autoantibodies negative and HbA1c goals not met

Consider – glucagon-like peptide 1 receptor agonist

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Consider –

glucagon-like peptide 1 receptor agonist

Treatment recommended for SOME patients in selected patient group

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes.[1] In individuals who are negative for autoantibodies, who are ≥10 years of age, and who do not meet their glycemic target on metformin plus lifestyle modifications, addition of either a glucagon-like peptide 1 (GLP-1) receptor agonist (or sodium-glucose cotransporter-2 [SGLT2] inhibitor) should be considered.[1]

A glycemic target of HbA1c <7% (<53 mmol/mol) is generally appropriate for children and adolescents with type 2 diabetes. More stringent HbA1c targets (such as <6.5% [<48 mmol/mol]) may be appropriate for certain individuals, including those with a short diabetes duration.[1]

Liraglutide (once-daily), exenatide extended-release (once-weekly), and dulaglutide (once-weekly) are the only GLP-1 receptor agonists approved for use in children ≥10 years of age for treatment of type 2 diabetes.

A randomized controlled trial (RCT) of liraglutide plus metformin, with or without basal insulin, improved glycemic control compared with placebo in children and adolescents with type 2 diabetes.[79] Similar impacts on glycemic control were reported in RCTs of exenatide and dulaglutide.[80][81]

Gastrointestinal adverse effects are the most common adverse effect associated with GLP-1 receptor agonists.

GLP-1 receptor agonists are contraindicated in those with past medical history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.

If the HbA1c target is not achieved after the addition of a GLP-1 receptor agonist to metformin, addition of an SGLT2 inhibitor as a third agent is recommended before initiating insulin therapy.[1]

Primary options

liraglutide: children ≥10 years of age: 0.6 mg subcutaneously once daily initially for 1 week, then 1.2 mg once daily, may increase according to response, maximum 1.8 mg/day

exenatide: children ≥10 years of age: 2 mg subcutaneously (extended-release) once weekly

dulaglutide: children ≥10 years of age: 0.75 mg subcutaneously once weekly initially for 4 weeks, may increase to 1.5 mg once weekly according to response

Consider – sodium-glucose cotransporter-2 inhibitor

Back

Consider –

sodium-glucose cotransporter-2 inhibitor

Treatment recommended for SOME patients in selected patient group

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes.[1] In individuals who are negative for autoantibodies, who are ages ≥10 years, and who do not meet their glycemic target on metformin plus lifestyle modifications, addition of either SGLT2 inhibitor (or GLP-1 receptor agonist) should be considered.[1]

Empagliflozin (either alone or in combination with other therapies) is approved in the US and Europe as an adjunct to diet and exercise to improve glycemic control in children ages ≥10 years. The safety and efficacy of empagliflozin in children were studied in a double-blind, randomized, placebo-controlled trial in patients ages 10 to 17 years with inadequately controlled type 2 diabetes.[82] The trial found that, at week 26, treatment with empagliflozin was superior in reducing HbA1c compared to placebo (0.84% HbA1c decrease with empagliflozin as compared to placebo).[82] Common adverse effects in children treated with empagliflozin were generally similar to those reported in adults, except there was a higher risk of hypoglycemia, regardless of whether they were taking other therapies for diabetes. However, no severe hypoglycemia cases were reported.[82]

If the HbA1c target is not achieved after the addition of an SGLT2 inhibitor to metformin, addition of a GLP-1 receptor agonist as a third agent is recommended before initiating insulin therapy.[1]

Primary options

empagliflozin: children ≥10 years of age: 10-25 mg orally once daily

Consider – insulin

Back

Consider –

insulin

Treatment recommended for SOME patients in selected patient group

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes.[1] In individuals who are negative for autoantibodies and who do not meet their glycemic target on metformin, lifestyle modifications, and a glucagon-like peptide 1 (GLP-1) receptor agonist, basal insulin should be added.[1] Basal insulin may be considered as an alternative to a GLP-1 receptor agonist in some patients (e.g., those who do not meet criteria for a GLP-1 receptor agonist).[1]

The American Diabetes Association recommends starting basal insulin at 0.5 units/kg/day and titrating the dose every 2-3 days based on blood glucose values.[1]

If glycemic targets are not met on escalating doses of basal insulin, addition of bolus insulin should be considered (i.e., with multiple injections of prandial insulin, or insulin pump therapy).[1] An insulin pump may be considered as an alternative to a regimen of multiple daily injections if the patient is able to manage the device safely.[1]

In children initially treated with insulin and metformin who are meeting glucose targets according to blood glucose monitoring values, insulin can be tapered over a period of 2-6 weeks by decreasing insulin dose by 10% to 30% every few days.[1] The UK Medicines and Healthcare products Regulatory Agency 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.[84]

See local specialist protocol for insulin dosing guidelines.

Primary options

insulin glargine

insulin degludec

insulin detemir

insulin NPH

Secondary options

insulin glargine

insulin degludec

insulin detemir

insulin NPH

-- AND --

insulin lispro

insulin aspart

insulin glulisine

Consider – metabolic surgery

Back

Consider –

metabolic surgery

Treatment recommended for SOME patients in selected patient group

May be appropriate for adolescents with class 2 obesity or higher (BMI >35 kg/m² or 120% of 95th percentile for age and sex, whichever is lower) and uncontrolled glycemia and/or serious comorbidities despite pharmacotherapy and lifestyle modifications.[1] Sleeve gastrectomy and Roux-en-Y gastric bypass are the most commonly performed bariatric procedures in adolescents.[85][86] Such surgery is generally safe and effective in adolescents, with short-term studies showing that it is comparable to metabolic surgery in adults in terms of major complications, readmissions and mortality.[85][86]

The World Gastroenterology Organisation and International Federation for the Surgery of Obesity and Metabolic Diseases note that bariatric surgery is the most effective treatment for severe obesity in adolescents.[85]

Further, studies have found that metabolic surgery may lead to type 2 diabetes remission in over 95% of adolescents. Other beneficial effects include improvements in cardiometabolic risk factors such as dyslipidemia and hypertension.[87][88]

pancreatic autoantibodies positive

Plus – initiate insulin + discontinue metformin

Back

Plus –

initiate insulin + discontinue metformin

Treatment recommended for ALL patients in selected patient group

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes. Individuals who are positive for pancreatic autoantibodies should initiate insulin therapy and discontinue metformin.[1] See Type 1 diabetes mellitus.

HbA1c ≥8.5%: no acidosis with or without ketosis

1st line – insulin

Back

1st line –

insulin

Children with marked hyperglycemia (HbA1c ≥8.5% [≥69 mmol/mol] or blood glucose ≥250 mg/dL [≥13.9 mmol/L]), polyuria, polydipsia, nocturia, and/or weight loss should be treated with basal insulin while metformin is initiated and titrated.[1]

The American Diabetes Association recommends starting basal insulin at 0.5 units/kg/day and titrating the dose every 2-3 days based on blood glucose values.[1]

See local specialist protocols for insulin dosing guidelines.

Primary options

insulin glargine

insulin degludec

insulin detemir

insulin NPH

Plus – metformin

Back

Plus –

metformin

Treatment recommended for ALL patients in selected patient group

Metformin should be initiated at the same time as insulin.[1]

Metformin improves hyperglycemia primarily through its suppression of hepatic glucose production, especially hepatic gluconeogenesis. It also causes anorexia and a modest amount of weight loss.

Primary options

Plus – lifestyle modifications

Back

Plus –

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

pancreatic autoantibodies negative and HbA1c goals not met

Consider – titrate insulin

Back

Consider –

titrate insulin

Treatment recommended for SOME patients in selected patient group

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes.[1] In individuals who are negative for autoantibodies and who do not meet their glycemic target on metformin, basal insulin, and lifestyle modifications, the dose of basal insulin should be titrated.[1] The American Diabetes Association recommends titrating the dose every 2-3 days based on blood glucose values.[1]

If glycemic targets are not met with escalating doses of basal insulin, addition of bolus insulin should be considered (i.e., with multiple injections of prandial insulin, or insulin pump therapy).[1] An insulin pump may be considered as an alternative to a regimen of multiple daily injections if the patient is able to manage the device safely.[1]

See local specialist protocols for insulin dosing guidelines.

Primary options

insulin glargine

insulin degludec

insulin detemir

insulin NPH

Secondary options

insulin glargine

insulin degludec

insulin detemir

insulin NPH

-- AND --

insulin lispro

insulin aspart

insulin glulisine

Consider – glucagon-like peptide-1 receptor agonist

Back

Consider –

glucagon-like peptide-1 receptor agonist

Treatment recommended for SOME patients in selected patient group

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes.[1] In individuals who are negative for autoantibodies, who are ≥10 years of age, and who do not meet their glycemic target on metformin, insulin, and lifestyle modifications, addition of either a GLP-1 receptor agonist (or SGLT2 inhibitor) should be considered.[1]

Gastrointestinal adverse effects are the most common adverse effect associated with GLP-1 receptor agonists.

GLP-1 receptor agonists are contraindicated in those with past medical history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.

The UK Medicines and Healthcare products Regulatory Agency 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.[84]

If the HbA1c target is not achieved after the addition of a GLP-1 receptor agonist to metformin and insulin, addition of an SGLT2 inhibitor as a fourth agent is recommended before intensifying insulin therapy.[1]

Primary options

liraglutide: children ≥10 years of age: 0.6 mg subcutaneously once daily initially for 1 week, then 1.2 mg once daily, may increase according to response, maximum 1.8 mg/day

exenatide: children ≥10 years of age: 2 mg subcutaneously (extended-release) once weekly

dulaglutide: children ≥10 years of age: 0.75 mg subcutaneously once weekly initially for 4 weeks, may increase to 1.5 mg once weekly according to response

Consider – sodium-glucose cotransporter-2 inhibitor

Back

Consider –

sodium-glucose cotransporter-2 inhibitor

Treatment recommended for SOME patients in selected patient group

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes.[1] In individuals who are negative for autoantibodies, who are ages ≥10 years, and who do not meet their glycemic target on metformin plus lifestyle modifications, addition of either a SGLT2 inhibitor (or a GLP-1 receptor agonist) should be considered.[1]

Empagliflozin (either alone or in combination with other therapies) is approved in the US and Europe as an adjunct to diet and exercise to improve glycemic control in children ages ≥10 years. The American Diabetes Association recommends empagliflozin for children with HbA1c <8.5% and no acidosis or ketosis who are not meeting their HbA1c goal on metformin alone (either instead of or in addition to a GLP-1 receptor agonist).[1] The safety and efficacy of empagliflozin in children were studied in a double-blind, randomized, placebo-controlled trial in patients ages 10 to 17 years with inadequately controlled type 2 diabetes.[82] The trial found that, at week 26, treatment with empagliflozin was superior in reducing HbA1c compared to placebo (0.84% HbA1c decrease with empagliflozin as compared to placebo).[82] Common adverse effects in children treated with empagliflozin were generally similar to those reported in adults, except there was a higher risk of hypoglycemia, regardless of whether they were taking other therapies for diabetes. However, no severe hypoglycemia cases were reported.[82]

If the HbA1c target is not achieved after the addition of an SGLT2 inhibitor to metformin and insulin, addition of a GLP-1 receptor agonist as a fourth agent is recommended before intensifying insulin therapy.[1]

Primary options

empagliflozin: children ≥10 years of age: 10-25 mg orally once daily

Consider – metabolic surgery

Back

Consider –

metabolic surgery

Treatment recommended for SOME patients in selected patient group

pancreatic autoantibodies positive

Plus – continue insulin + discontinue metformin

Back

Plus –

continue insulin + discontinue metformin

Treatment recommended for ALL patients in selected patient group

Patients with new-onset diabetes should be tested for pancreatic autoantibodies to exclude a diagnosis of type 1 diabetes. Individuals who are positive for pancreatic autoantibodies should continue insulin therapy and discontinue metformin.[1] See Type 1 diabetes mellitus.

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Type 2 diabetes in children

Treatment algorithm

ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome

intravenous insulin + hydration

Primary options

switch to subcutaneous insulin

Primary options

metformin

Primary options

HbA1c <8.5%: no acidosis or ketosis

metformin

Primary options

lifestyle modifications

glucagon-like peptide 1 receptor agonist

Primary options

sodium-glucose cotransporter-2 inhibitor

Primary options

insulin

Primary options

Secondary options

metabolic surgery

initiate insulin + discontinue metformin

HbA1c ≥8.5%: no acidosis with or without ketosis

insulin

Primary options

metformin

Primary options

lifestyle modifications

titrate insulin

Primary options

Secondary options

glucagon-like peptide-1 receptor agonist

Primary options

sodium-glucose cotransporter-2 inhibitor

Primary options

metabolic surgery

continue insulin + discontinue metformin