Approach

As there is no known common underlying pathogenetic mechanism unifying all of the components of metabolic syndrome, it is not clear whether this syndrome can be treated in itself. It is therefore necessary to concentrate on the treatment of the specific features of the condition separately, with the overall goals of reducing the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM). Reducing excess adiposity and resultant insulin resistance is the most reliable unifying therapeutic approach.

Lifestyle modification

Intensive lifestyle modification with modest weight loss is a well-established therapeutic strategy.[83] It results in about 40% reduction in the prevalence of metabolic syndrome.[84] Weight loss has many beneficial effects on all of the features of metabolic syndrome. It reduces blood pressure (BP), increases high-density lipoprotein (HDL)-cholesterol, reduces triglyceride and glucose levels, and improves insulin resistance.[85] The primary goal is for overweight/obese patients to reduce total body weight by 10%. A secondary goal is to achieve a normal body mass index (BMI) (i.e., <25 kg/m²).[13]​ This can be achieved through diet and physical activity.

Diet:

  • Patients with metabolic syndrome obtain a favorable outcome from a diet low in saturated fats and high in unsaturated fats, high in complex unrefined carbohydrates and fiber (10-25 g/day), and low in added sugars and sodium (restricted to 65-100 mmol daily), as sodium is associated with hypertension.[4][13]​​[86][87][88][89][90] [ Cochrane Clinical Answers logo ]

  • Increased fiber intake is associated with reductions in total and low-density lipoprotein (LDL)-cholesterol and diastolic blood pressure.[91]

  • Carbohydrates should constitute 40% to 65% of the total calorie intake, as a low-carbohydrate diet is associated with a reduced incidence of CVD and type 2 DM.​[92][93] Protein should constitute 10% to 35% in all patients except those with nephropathy.[4]

  • Fats should constitute 20% to 35% of the total calorie intake and, of these, saturated fats must be reduced to <7%, trans-fatty acids to <1%, and cholesterol to <200 mg/day.[4][13]​​[86]

  • Monounsaturated fats such as those derived from plant sources, including olive oil and soybean oil, should be consumed, as these have beneficial effects on atherogenic dyslipidemia. Similarly, n-3-polyunsaturated fatty acids (mainly from fish) should constitute about 10% of calorie intake, as these have cardioprotective effects.[86]

  • The Mediterranean diet, which is rich in fiber, monounsaturated fats, and polyunsaturated fats (with a low ratio of omega-6 to omega-3 fatty acids), low in animal protein, and based mainly on fruit, vegetables, fish, nuts, whole grains, and olive oil, seems to be effective in reducing the prevalence of metabolic syndrome and associated CVD.[60][66]​ It also reduces the risk of developing DM, especially in patients with high CVD risk.[94]

  • PolyGlycopleX (PGX), a viscous functional polysaccharide, has shown promising effects on lipidemia and glycemia improvement in adults with metabolic syndrome.[95]

  • Both a low-glycemic load (LGL) and a low-fat diet can reduce body weight and metabolic disturbances similarly, but the LGL diet seems to be more suitable for people with metabolic syndrome.[96][97]

  • Calories in sugar-sweetened beverages lead to increased caloric intake. Plasma triglycerides are increased by sugar-sweetened beverages, an increase that appears to be due to fructose rather than to glucose in sugar.[98]

  • Regarding the best strategy for achieving adherence to meaningful lifestyle change, one meta-analysis showed that a team-based, interactive approach with high-frequency contact and motivated patients has the largest and most lasting impact on weight management.[99]

Physical activity:

  • Cumulative evidence shows that regular moderate to intense physical activity may prevent metabolic syndrome and that activity of greater intensity may carry greater benefit.[35][89][100]​​

  • Exercise may be beneficial beyond its effect on weight loss by more selectively removing abdominal fat. In particular, aerobic exercise seems to have a dose-response effect on visceral adiposity.[101]

  • The standard daily exercise recommendation is a minimum of 30 minutes of moderate to intense physical activity such as brisk walking.[4][13]​​[102][103]

  • Moreover, diet and physical activity promotion programs for prevention of type 2 diabetes are also cost effective in persons at increased risk.[104]

  • Exercise-focused intervention using telemonitoring systems has been shown to further reduce metabolic syndrome severity, while also improving mental health and working ability.[105]

In addition to the above, smoking cessation is mandatory for patients with metabolic syndrome.​[14][85]

Pharmaceutical and surgical interventions for weight loss

Weight reduction drugs:

  • Guidelines on obesity recommend considering pharmaceutical therapy for weight loss as an adjunct to diet and exercise in patients with a BMI of ≥30 kg/m², or ≥27 kg/m² in the presence of comorbidities related to excess adiposity.[4][106][107]​​

  • Semaglutide is a glucagon-like peptide-1 receptor agonist targeting areas of the brain that regulate appetite and food intake. Originally approved for the treatment of type 2 diabetes, semaglutide is now also indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with BMI ≥30 kg/m², or ≥27 kg/m² in the presence of at least one weight-related comorbidity.[108] Randomized controlled trial data showed that patients receiving semaglutide lost an average of 6% to 16% of their total body weight compared with controls, when combined with other behavioral modifications.[109][110][111]​ Analysis of data from phase 3 trials found that semaglutide may also improve cardiometabolic risk factors (waist circumference, blood pressure, fasting plasma glucose, fasting serum insulin, lipids) and reduce use of antihypertensive/lipid-lowering medication compared with placebo in adults with overweight/obesity without diabetes; however benefits were not maintained following treatment discontinuation.​[112]​ In the SELECT trial, semaglutide was found to reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in patients with pre-existing cardiovascular disease and overweight or obesity but without diabetes, compared with placebo at a mean follow-up of 39.8 months.[113]

  • Phentermine/topiramate is an oral combination therapy containing phentermine, an amphetamine/appetite suppressant, and topiramate, an anticonvulsant. It is approved for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Phentermine/topiramate is effective in reducing weight when combined with lifestyle interventions, and may also improve markers of cardiovascular system function such as blood pressure, total cholesterol, triglycerides, and blood glucose levels.[114]​​[115][116][117]​​ Phentermine/topiramate should be used with caution and at lower doses in patients with hepatic or renal impairment, and in those with hypertension or arrhythmias, due to the adrenergic effects of phentermine. Phentermine is a controlled substance due to its abuse potential, and should not be prescribed for patients with a history of substance abuse.

  • Orlistat reduces fat absorption by binding to pancreatic lipases, partially inhibiting the hydrolysis of triglycerides into absorbable free fatty acids and monoacylglycerols.[101] This has been found to result in significant weight loss compared with placebo, with rebound weight gain if discontinued.[118] In association with a hypocaloric diet, orlistat has a favorable outcome on several cardiovascular risk factors, including BP and fasting glucose, triglyceride, and LDL-cholesterol levels in patients with metabolic syndrome and type 2 DM.[119] Orlistat plus lifestyle interventions reduced the incidence of type 2 DM by 37% in high-risk patients compared with placebo and lifestyle changes alone.[120]

  • Bupropion/naltrexone and liraglutide are also approved for the treatment of obesity. Bupropion/naltrexone acts by nonselectively inhibiting dopamine, as well as norepinephrine transporters (bupropion) and opioid receptors (naltrexone). Liraglutide is a glucagon-like peptide-1 receptor agonist, which acts by increasing satiety and insulin secretion.[121]​​

Bariatric surgery:

  • The NIH has established guidelines for the surgical therapy of class III obesity (BMI ≥40). According to these guidelines, bariatric surgery should be considered in patients with a BMI of ≥40 kg/m², or ≥35 kg/m² in the presence of significant comorbidities.[122]

  • Surgical procedures include gastric banding, gastric bypass (principally Roux-en-Y), gastroplasty (principally vertical banded gastroplasty), biliopancreatic diversion, biliary intestinal bypass, ileogastrostomy, and jejunoileal bypass.

  • Bariatric surgery significantly ameliorates all the components of metabolic syndrome, results in substantial postoperative weight loss (20% to 32% depending on the procedure), and reduces overall mortality compared with conventional therapy.[123][124][125][126][127]

  • In one meta-analysis, bariatric surgery was the most effective strategy in preventing type 2 diabetes, compared with diet and/or physical activity or antidiabetic drugs in morbidly obese subjects.[128]

  • See Obesity in adults.

Cardiovascular disease prevention with low-dose aspirin

As metabolic syndrome is also regarded as a prothrombotic and proinflammatory state, low-dose aspirin may be considered for patients ages 40-59 years who have a 10-year CVD risk of 10% or more.[129]​ The benefit of aspirin must be weighed against the risk of hemorrhage.

Treatment of insulin resistance and hyperglycemia

In addition to weight reduction with diet and physical activity, insulin resistance can be further reduced with drugs in those with metabolic syndrome and new-onset type 2 DM. It should be noted no pharmacologic agent is officially approved to raise insulin sensitivity, and it has not been conclusively shown whether these agents prevent the progression to type 2 DM in patients with impaired glucose tolerance.[4]

Metformin:

  • This insulin-sensitizing agent has long been used for the treatment of type 2 DM.[14][80][85]

  • It has been shown to reduce the progression to type 2 DM in patients with impaired glucose tolerance[130] and to reduce the development of new-onset CVD in obese patients with type 2 DM in the United Kingdom Prospective Diabetes Study (UKPDS).[131] However, there are no cardiovascular end-point studies in patients with metabolic syndrome treated with metformin.

Thiazolidinediones:

  • These peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists improve tissue sensitivity to insulin in patients with type 2 DM, thus reducing fasting blood glucose levels and HbA1c.[132]

  • The 2 commercially available thiazolidinediones (rosiglitazone and pioglitazone) have similar beneficial effects on glycemic control, insulin sensitivity, and insulin secretion.[133]

  • Pioglitazone seems to have a more beneficial effect than rosiglitazone on the plasma lipid profile.[133] In the prospective pioglitazone clinical trial in macrovascular events (PROACTIVE) study, pioglitazone significantly reduced the risk of death, nonfatal myocardial infarction, and stroke compared with placebo in patients with type 2 DM and, in addition to other drugs used in the secondary prevention of diabetes and CVD, reduced signs of macrovascular disease.[134]

  • Rosiglitazone significantly increased the risk of myocardial infarction and death from CVD.[135] This has reduced its use in type 2 DM, and rosiglitazone has been removed from the treatment algorithm of the American Diabetes Association and the European Association for the Study of Diabetes.[136]

Treatment of dyslipidemia

LDL-cholesterol is the main target of cholesterol-lowering therapy.​[137][138][139][140]​​​​ It has been postulated that each 10% decrease in LDL-cholesterol or 10% increase in HDL-cholesterol is associated with an 11% risk decrease for CVD.[141]

Initiating treatment for LDL-cholesterol depends on the absolute risk of coronary heart disease (CHD) based on risk stratification.[3] Major risk factors include: cigarette smoking, hypertension (BP 140/90 mmHg or greater or on antihypertensive medication), low HDL-cholesterol (<40 mg/dL), family history of premature CHD (CHD in male first-degree relative <55 years of age; CHD in female first-degree relative <65 years of age), and age (men older than 45 years of age; women older than 55 years of age). CHD risk equivalents include clinical manifestations of non-coronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease [transient ischemic attacks or cerebrovascular accidents of carotid origin or >50% obstruction of a carotid artery]), diabetes, and two or more risk factors with a 10-year risk for CHD >20%.

Statins are the major LDL-cholesterol-lowering agents and reduce LDL-cholesterol by 30% to 60% depending on the dose and specific type of statin used. Statins also increase HDL-cholesterol by 5% to 10% and reduce triglycerides by 7% to 30%.[4][14][85]​​​ They have several other effects independent of lipid lowering, including modulating endothelial function, stabilizing plaque, and anti-inflammatory and antithrombotic effects, which further contribute to reducing the CVD risk associated with these drugs.[118] These pleiotropic actions have been shown in patients with either impaired fasting glucose or impaired glucose tolerance associated with metabolic syndrome.[142]

Guidelines provide specific recommendations for management of dyslipidemia.

  • 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS):[139]​

    • Patients at very high cardiovascular risk are those with: documented atherosclerotic CVD, either clinical or unequivocal on imaging (acute coronary syndrome, stroke, peripheral arterial disease, the presence of significant plaque [>50% stenosis] on coronary angiography or CT scan or carotid ultrasound); diabetes mellitus, with target organ damage or at least three major CVD risk factors; early onset of type 1 DM of >20 years' duration; severe chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <30 mL/minute/1.73 m²); calculated SCORE ≥10% for 10-year risk of fatal CVD; familial hypercholesterolemia (FH) with CVD or with another major CVD risk factor. For these patients, an LDL-cholesterol reduction from baseline of ≥50% and an LDL-cholesterol goal of <55 mg/dL are recommended. ESC: SCORE risk charts Opens in new window

    • Patients at high cardiovascular risk are those with: markedly elevated single risk factors (total cholesterol >310 mg/dL or LDL-cholesterol >190 mg/dL or blood pressure ≥180/110 mmHg); patients with FH without other major risk factors; patients with DM without target organ damage or with DM duration ≥10 years or with another additional risk factor; moderate CKD (eGFR 30-59 mL/minute/1.73 m²); calculated SCORE ≥5% and <10% for 10-year risk of fatal CVD. For these patients, an LDL-cholesterol reduction from baseline of ≥50% and an LDL-cholesterol goal of <70 mg/dL are recommended. ESC: SCORE risk charts Opens in new window

    • Patients at moderate cardiovascular risk are considered to be: young patients with diabetes mellitus (<35 years old for type 1 and <50 years old for type 2) with duration <10 years, without other risk factors; calculated SCORE ≥1% and <5% for 10-year risk of fatal CVD. For these patients, the LDL-cholesterol target is <100 mg/dL. ESC: SCORE risk charts Opens in new window

    • Patients at low cardiovascular risk are considered those with a calculated SCORE <1% for 10-year risk of fatal CVD. The LDL-cholesterol target for these patients is <115 mg/dL. ESC: SCORE risk charts Opens in new window

    • NonHDL-cholesterol and apolipoprotein B should be considered secondary targets. Proposed targets for apolipoprotein B are <65 mg/dL, <80 mg/dL, and <100 mg/dL for people at very high, high, and moderate cardiovascular risk, respectively.[139]​ The targets for nonHDL-cholesterol are <85 mg/dL, <100 mg/dL, and <130 mg/dL for people at very high, high, and moderate cardiovascular risk, respectively.[139] However, these targets have received a moderate grading in the ESC/EAS guidelines as they have not been extensively studied in randomized controlled trials.

    • Lipoprotein (a) [Lp(a)] measurement should be considered at least once in each adult person’s lifetime to identify those with very high inherited Lp(a) levels ≥180 mg/dL, which is equivalent to the lifetime risk of FH-associated CVD.[139]

    • Apolipoprotein B analysis is recommended for risk assessment, particularly in people with hypertriglyceridemia, DM, obesity or metabolic syndrome, or very low LDL-cholesterol levels.

  • 2018 American Heart Association/American College of Cardiology/multi society guidelines:[140]

    • Patients with atherosclerotic cardiovascular disease (ASCVD) who are at very high risk of future events are treated with high-intensity statin therapy (daily dose lowers LDL-cholesterol by ≥50%) or maximal statin therapy. Very high risk is defined as a history of multiple major ASCVD events (recent acute coronary syndrome [within the past 12 months], myocardial infarction other than the recent acute coronary syndrome, ischemic stroke, symptomatic peripheral arterial disease [claudication with ankle brachial index <0.85, previous revascularization, or amputation]) or one major ASCVD event and multiple high-risk conditions (ages ≥65 years, heterozygous family history, history of previous coronary artery bypass graft or percutaneous coronary intervention, diabetes mellitus, hypertension, chronic kidney disease, current smoking, persistently elevated LDL-cholesterol [≥100 mg/dL] despite maximally tolerated therapy, history of congestive heart failure). Patients with ASCVD not at very high risk of future events and ages ≤75 years are treated with high-intensity statin therapy, or with moderate-intensity statin therapy (daily dose lowers LDL-cholesterol 30% to <50%) if high-intensity therapy is not tolerated; patients ages >75 years are treated with moderate- or high-intensity statin therapy.

    • Patients ages 20-75 years without ASCVD but who have LDL-cholesterol ≥190 mg/dL should be treated with high-intensity statin therapy, or moderate-intensity statin therapy if they are not a candidate for high-intensity statin therapy.

    • People ages 40-75 years without ASCVD but who have diabetes mellitus should be started on moderate-intensity statin therapy regardless of 10-year ASCVD risk. In adults with diabetes and LDL-cholesterol 70-189 mg/dL, it is reasonable to assess 10-year ASCVD risk and start high-intensity statin therapy in those who have multiple ASCVD risk factors.

    • People with metabolic syndrome, without ASCVD or diabetes, ages 40-75 years with LDL-cholesterol 70-189 mg/dL: estimate 10-year ASCVD risk and if borderline risk (5.0% to <7.5%) then discuss moderate-intensity statin therapy; the patient-clinician discussion should consider the potential for ASCVD risk-reduction benefits and adverse effects, drug-drug interactions, and patient preferences for treatment. If intermediate risk (≥7.5% to <20%), start moderate-intensity statin therapy; if uncertain can use coronary artery calcification (CAC) score (CAC=0: lowers risk; consider no statin unless diabetes, family history of premature CHD, smoking; CAC=1-99: favors statin, especially if ages >55 years; CAC=100+ and/or ≥75th percentile: begin statin). If high risk, ≥20%, start high-intensity statin therapy.

    • Statins are also recommended as the drug of choice for reducing CVD risk in high-risk individuals with hypertriglyceridemia (triglyceride level >200 mg/dL).[140]

    • The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%. Serious hepatotoxicity is even rarer (approximately 0.001%). The risk of statin-induced newly diagnosed DM is approximately 0.2% per year of treatment, depending on the underlying risk factors for DM. This suggests that muscle symptoms are usually not caused by pharmacologic effects of statins.[143]

  • The United States Preventive Services Task Force (USPSTF) recommends that adults ages 40-75 years who have one or more cardiovascular risk factors (i.e., dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year cardiovascular disease risk of 10% or greater should be started on a statin. Those with 10-year risk of 7.5% to less than 10% may selectively be offered a statin.[144]

If the LDL-cholesterol goal is not achieved, other lipid-lowering drugs can be added to statins. The choice of lipid-lowering agent is based on the lipid profile of the individual patient.

  • Ezetimibe is very effective in combination with statins. It acts by inhibiting cholesterol absorption and reduces LDL-cholesterol by an average of 20% to 30%.[145][146]​ In the IMPROVE-IT trial, which compared statin monotherapy with statin and ezetimibe combination in patients with recent acute coronary syndrome, the benefit of adding ezetimibe to statin was enhanced in those with diabetes (and in high-risk patients without diabetes), with greater reductions in acute ischemic events.[147]

  • Bile acid sequestrants such as colesevelam also effectively reduce LDL-cholesterol by 15% to 30%, but successful treatment requires a patient with significant discipline and tenacity to mix the granular powder form of these agents.[148] In combination with atorvastatin, colesevelam reduces LDL-cholesterol by about 25%.[149]

  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (evolocumab, alirocumab) reduce LDL-C by approximately 50% to 60% and result in greater LDL-C goal achievement when added to statins in a variety of populations.[150][151][152]​​​​ Secondary analysis of the FOURIER trial found that addition of evolocumab to statin therapy significantly reduced cardiovascular events in patients with ASCVD and metabolic syndrome without an increase in serious safety events, including new-onset diabetes.[153]

  • Fibrates (e.g., fenofibrate) activate PPAR-alpha, a nuclear receptor protein that affects the expression of target genes involved in cell proliferation, cell differentiation, and immune and inflammatory responses.[154][155]​ They decrease triglyceride levels by 25% to 50% and LDL-cholesterol by up to 30% (although these may be increased in patients with low HDL-cholesterol and high triglycerides), and increase HDL-cholesterol by 5% to 15%. Reducing triglycerides leads to a transformation of small, dense LDL-cholesterol particles into more normal-sized particles.[4] When LDL-cholesterol is controlled, fibrates are the most effective agents for lowering triglycerides and increasing HDL-cholesterol. In one cohort study of adults with metabolic syndrome receiving statin treatment, the risk of major cardiovascular events was reduced in those who received additional treatment with fenofibrate, compared with those who received statin alone.[156]​ 

  • Omega-3 polyunsaturated fatty acids, especially eicosapentaenoic and docosahexaenoic acids, are particularly efficacious in lowering triglycerides, decreasing these by 20% to 40%, although they raise LDL-cholesterol by 5% to 10% with no effect on HDL-cholesterol.[4] However, atrial fibrillation has been identified as a common, dose-dependent adverse reaction in patients taking high doses of omega-3-acid ethyl esters. Healthcare professionals should monitor patients for signs of atrial fibrillation and discontinue omega-3-acid ethyl esters if atrial fibrillation develops. Patients should be advised to report symptoms such as palpitations, dizziness, or irregular heartbeats promptly. Meta-analyses looking at the association between omega-3 fatty acids and risk of cardiovascular events have shown inconsistent results.[157][158][159][160]​​ In high-risk patients with triglyceride levels between 135-499 mg/dL despite statin treatment, icosapent ethyl (the ethyl ester of the omega-3 fatty acid eicosapentaenoic acid) should be considered in combination with a statin.[140] In the REDUCE-IT trial, use of icosapent ethyl in patients with increased triglyceride concentrations was associated with reduced risk of ischemic events, compared with those who received placebo (though overall risk reduction is uncertain as mineral oil placebo may have increased risk in control group).​[161][162]​​​

  • Niacin is another alternative for reducing triglycerides and non-HDL-cholesterol. This drug can be used as monotherapy or in combination with LDL-cholesterol-lowering agents.[163] It is the most potent agent for elevating HDL-cholesterol levels, increasing these by 5% to 15%, and for increasing the particle size of HDL-cholesterol.[164] It is also the only drug that lowers lipoprotein (a) levels in people with diabetes.[165][166] Several adverse effects such as flushing and hyperglycemia have limited its use.[4] The Heart Protective Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE [n=25,000 adults]) trial results showed no benefit in high risk patients.[167]As a result of this, in January 2013, the European Medicines Agency withdrew the niacin/laropiprant combination from the European market.

  • Plant sterols and stanols, which are available as food additives in a variety of dairy products, including margarine and yogurt, have a modest effect on LDL-cholesterol in combination with statins.[168] The average reduction in LDL-cholesterol across all studies has been 9% with a mean daily plant sterol (phytosterol) dose of 2.15 g. LDL-cholesterol reduction with stanols is optimized with an intake of about 2 g/day. Greater quantities do not reduce serum LDL levels much further.[168]

  • Creatine kinase and aminotransferases can become elevated due to lipid-lowering medication, especially statins and fibrates, and should be monitored. Caution should thus be taken with the co-administration of statins and fibrates.

See Hypercholesterolemia and Hypertriglyceridemia.

Treatment of hypertension

The target BP for most adults is <130/80 mmHg.[169][170]​​​ If target cannot be achieved with lifestyle modification, antihypertensive medication is required.

Although no specific class of antihypertensive drug is regarded as uniquely efficacious for metabolic syndrome, ACE inhibitors or angiotensin-II receptor antagonists are the preferred drugs, particularly in the presence of type 2 DM or chronic kidney disease, as they significantly reduce the incidence of albuminuria and progression to nephropathy.[4][85]

See Essential hypertension.

Management of associated long-term comorbidities

Hypogonadism

  • Hypogonadism in males is commonly associated with metabolic syndrome.

  • In addition to improving symptoms of hypogonadism, testosterone replacement therapy seems to improve metabolic control (glycemic control, insulin sensitivity, and lipid parameters) as well as central obesity in patients with metabolic syndrome and hypogonadism.[48][49][171]

  • See Hypogonadism in men.

  • In women, hormone-replacement therapy (HRT) has been shown to improve lipid profiles, insulin sensitivity and secretion, and visceral adiposity, but the effects depend on the type, dose, and route of administration of the HRT.[50][172]​ CVD risk may be reduced if HRT is initiated during the early postmenopausal period (women ages <60 years or within ten years since the final menstrual period).

Polycystic ovary syndrome (PCOS)

  • PCOS seems to aggravate insulin resistance and metabolic risk factors in obese women, whereas in those of normal weight, PCOS is not associated with impaired insulin sensitivity.[46]

  • Patients with PCOS share features of metabolic syndrome such as obesity, insulin resistance, and dyslipidemia; these components are treated separately as per guidelines. Patients also require referral to a gynecologist or endocrinologist.

  • See Polycystic ovary syndrome.

Metabolic dysfunction-associated steatotic liver disease (MASLD)

  • MASLD is considered the hepatic manifestation of metabolic syndrome and is associated with obesity, dyslipidemia, and type 2 diabetes mellitus.[173][174]

  • Lifestyle modification, including weight loss, physical activity, and dietary changes, is the first-line therapy. There are no licensed drug treatments for MASLD, although use of pioglitazone or vitamin E may be considered for selected patients. Liver transplantation is an option for those with end-stage liver disease.

  • See Metabolic dysfunction-associated steatotic liver disease​.

Obstructive sleep apnea

  • Obstructive sleep apnea (OSA) frequently coexists with metabolic syndrome (some use the term "syndrome Z" to refer to the two conditions together), and obesity is a key risk factor for development of OSA; however, there is also evidence that OSA leads to development of metabolic syndrome as intermittent hypoxia and arousal increase insulin resistance.[54][55][56]

  • Some studies suggest that treatment of OSA (e.g., with continuous positive airway pressure) has a direct positive impact on components of metabolic syndrome; though this is not yet established.[175][176]​​

  • See Obstructive sleep apnea.

Chronic kidney disease (CKD)

  • Metabolic syndrome and its components (obesity, hypertension) are associated with development and progression of CKD.[177]​ Renal injury may occur directly through renal compression and lipotoxicity and indirectly through hypertension and insulin resistance.[177]

  • Optimizing management of the metabolic syndrome components is important to slow the progression of CKD. However, some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information.

  • ACE inhibitors or angiotensin-II receptor antagonists are the preferred drugs for the management of hypertension in those with CKD as they significantly reduce incidence of albuminuria and progression to nephropathy.[4][85]

  • An individualized multidisciplinary approach is recommended for patients with metabolic syndrome and CKD, including consultation with nephrology and endocrinology specialists.[177]

  • See Chronic kidney disease.

Use of this content is subject to our disclaimer