Treating the metabolic syndrome

The metabolic syndrome (MS), a cluster of metabolic abnormalities with insulin resistance as its central component, is increasing in prevalence and is associated with an increased risk of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Current evidence supports an aggressive intervention approach that comprises lifestyle modification in conjunction with drug treatment of the MS components. Healthier eating and regular exercise greatly reduce waistline and body mass index, lower blood pressure and improve lipid profile. Lifestyle modification has been proven to prevent T2DM development. Nevertheless, appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs. Only severely obese patients require specific drug treatments. Very often, drug combinations will be necessary to manage multiple risk factors. As we progress in the understanding of the pathophysiology of the MS, new targets for therapies will probably be identified and new treatments will prove to be even more efficacious than those currently available for the management of this life-threatening condition.     

Treating the metabolic syndrome

The metabolic syndrome (MS), a cluster of metabolic abnormalities with insulin resistance as its central component, is increasing in prevalence and is associated with an increased risk of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Current evidence supports an aggressive intervention approach that comprises lifestyle modification in conjunction with drug treatment of the MS components. Healthier eating and regular exercise greatly reduce waistline and body mass index, lower blood pressure and improve lipid profile. Lifestyle modification has been proven to prevent T2DM development. Nevertheless, appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs. Only severely obese patients require specific drug treatments. Very often, drug combinations will be necessary to manage multiple risk factors. As we progress in the understanding of the pathophysiology of the MS, new targets for therapies will probably be identified and new treatments will prove to be even more efficacious than those currently available for the management of this life-threatening condition.     

Managing cardiovascular risk in patients with metabolic syndrome

Metabolic syndrome consists of a cluster of cardiovascular (CV) and metabolic risk factors (e.g., abdominal obesity, hypertension, elevated levels of fasting plasma glucose and triglycerides, and low levels of high-density lipoprotein cholesterol [HDL-C]) and is associated with an increased risk for type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). Because the risks for CVD and type 2 DM are highly variable among patients with metabolic syndrome, it is essential to assess a patient's risks before identifying specific treatment or lifestyle interventions. The major risk factors for CVD are smoking, hypertension, elevated levels of total and low-density lipoprotein cholesterol, low levels of HDL-C, and older age. In patients at low risk for CV events, lifestyle interventions (i.e., weight loss and increased physical activity) may be sufficient to control the components of metabolic syndrome and to reduce the risk for type 2 DM and CVD. Patients who are at high risk, however, must receive aggressive drug therapy in addition to lifestyle interventions. The following factors need to be targeted: obesity (particularly abdominal obesity), dyslipidemia, hypertension, and prothrombotic/proinflammatory states. Drugs with various and complementary mechanisms of action, including drugs targeting lipid metabolism, may be effective in controlling these factors and thereby delaying or preventing CV events and type 2 DM.     

Successful control of dyslipidemia in patients with metabolic syndrome: focus on lifestyle changes

Approaches to controlling dyslipidemia in patients with metabolic syndrome must take into consideration a patient's individual characteristics and underlying lipid disorder. Some patients will require pharmacologic therapy, whereas others can be controlled with lifestyle changes alone. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines recommend that patients with at least 3 of the following clinical variables be designated as having metabolic syndrome: abdominal obesity as reflected in increased waist circumference; a low high-density lipoprotein cholesterol (HDL-C) level; an elevated triglyceride level; elevated blood pressure or treatment with antihypertensive medications; and/or elevated fasting plasma glucose or treatment with antidiabetic medications. Unless patients with metabolic syndrome change their lifestyle, existing cardiovascular and metabolic risk factors will worsen or new risk factors will develop. This helps explain why these patients are at increased risk for developing type 2 diabetes mellitus (DM) and coronary heart disease (CHD). The lifestyle changes recommended by NCEP ATP III for controlling dyslipidemia (i.e., elevated levels of triglycerides and decreased levels of HDL-C) in patients with metabolic syndrome or type 2 DM include (1) reduced intake of saturated fats and dietary cholesterol, (2) intake of dietary options to enhance lowering of low-density lipoprotein cholesterol, (3) weight control, and (4) increased physical activity. If lifestyle changes are not successful for individuals at high risk of developing CHD, or for those who currently have CHD, a CHD risk equivalent, or persistent atherogenic dyslipidemia, then pharmacotherapy may be necessary as defined by NCEP ATP III guidelines.     

二甲双胍对合并代谢综合征的2型糖尿病患者代谢指数的影响

目的观察二甲双胍对合并代谢综合征的2型糖尿病患者代谢指数的影响。方法将45例正使用诺和灵30R治疗的合并代谢综合征的2型糖尿病患者随机分为两组,对照组维持原治疗方案,治疗组加用二甲双胍（0．5g3次／d）观察随访12周。结果治疗组与联合二甲双胍治疗前相比,联合二甲双胍治疗后空腹血糖,糖化血红蛋白（HbA1c）,甘油三酯（TG）,总胆固醇（TC）,体质指数（BMI）,腰围（WC）明显下降（尸〈0．001）。血压无明显改变。对照组的上述指标与治疗前相比差异无统计学意义（P〉0．05）。结论对合并代谢综合征的2型糖尿病患者联合应用二甲双胍可有效控制血糖、血脂,减轻体重。     

Youth-Onset Type 2 Diabetes Mellitus: Lessons Learned From the TODAY Study

Type 2 diabetes mellitus is increasingly diagnosed in obese children and adolescents. Evidence suggests that this disease commonly progresses more rapidly in youth compared with adults and is associated with high rates of early microalbuminuria, hypertension, and dyslipidemia. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study was the first multiethnic, multicenter randomized trial in the United States to compare 3 treatment approaches in obese youth with new-onset type 2 diabetes (n=699; ages 10-17 years): monotherapy with metformin, metformin with rosiglitazone, and metformin with an intensive lifestyle intervention. The primary outcome was glycemic control. Diabetes-related complications and cardiovascular risk factors were also examined. Approximately half of the participants could not maintain glycemic control by using metformin alone. Combination therapy with metformin and rosiglitazone resulted in better durability of glycemic control, and metformin plus intensive lifestyle intervention was intermediate but not superior to metformin alone. Deterioration in glycemic control was associated with rapid loss of beta cell function, not worsened insulin sensitivity, and could not be explained by differences in adherence or body mass index. After 3.9 years, 236 (33.8%) of participants had hypertension and 116 participants (16.6%) had microalbuminuria. Only 55.9% of participants had a low-density lipoprotein cholesterol level less than 100 mg/dL (to convert to mmol/L, multiply by 0.0259) after 3 years, and 71 of 517 participants (13.7%) had retinopathy. The significance of the findings from this important trial for the management of youth and young adults with youth-onset type 2 diabetes and its complications is discussed. An aggressive multifaceted approach is needed to prevent or forestall premature microvascular and macrovascular complications in youth-onset type 2 diabetes.     

利拉鲁肽对新疆维吾尔族2型糖尿病肥胖患者的疗效研究

目的探讨利拉鲁肽治疗新疆维吾尔族2型糖尿病(T2DM)肥胖患者的疗效。方法纳入67例单用二甲双胍后血糖控制不理想的肥胖T2DM患者,将其随机分为二甲双胍组(单用二甲双胍)和二甲双胍+利拉鲁肽组(联合应用二甲双胍和利拉鲁肽),治疗周期为12周。分别在基线、治疗12周后检测2组患者腹部内脏脂肪面积(VA)、体脂百分比(PBF)、体脂肪量,同时测量一氧化氮(NO)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、游离脂肪酸(FFA)等相关指标,计算体质量指数(BMI)、腰臀比(WHR),采取病例对照的试验方法进行分析。结果治疗12周后,二甲双胍+利拉鲁肽组较二甲双胍组,患者体质量(W)、WHR、腰围(WC)、空腹血糖(FBG)、体脂肪量和腹内脂肪(VA)均明显下降,差异有统计学意义(P0.05)。结论接受利拉鲁肽治疗的T2DM肥胖患者在血糖、血脂得到控制的同时,能获得降低W、改善血管内皮功能、减少内脏脂肪的收益。     

Effect of orlistat on weight regain and cardiovascular risk factors following a very-low-energy diet in abdominally obese patients: a 3-year randomized, placebo-controlled study

OBJECTIVE: To investigate the efficacy of orlistat on the maintenance of weight loss over 3 years following a major weight loss induced by very-low-energy diet (VLED) in obese patients with metabolic risk factors such as dyslipidemia, impaired fasting glucose, and diet-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: Initially, weight loss was induced by an 8-week VLED (600-800 kcal/day) in 383 patients with a mean BMI of 37.5 kg/m(2) (range 30.0-45.2). Those who lost > or = 5% of their body weight (309 of 383 patients) were then randomized to receive lifestyle counseling for 3 years together with either orlistat 120 mg t.i.d. or matching placebo capsules. Primary end points were the maintenance of > or = 5% weight loss after 3 years. Additionally, differences in the development of type 2 diabetes between orlistat and placebo were analyzed. RESULTS: The VLED induced a mean weight loss of 14.4 +/- 2.0 kg among the subsequently randomized patients. The mean weight gain after 3 years was lower with orlistat than with placebo (4.6 +/- 8.6 vs. 7.0 +/- 7.1 kg; P < 0.02). The number of participants who achieved > or =5% weight loss also favored orlistat (67 vs. 56%; P = 0.037). Waist circumference was significantly more reduced in the orlistat group (P < 0.05), but no other differences in the risk factors were observed between the two groups. The incidences of new cases of type 2 diabetes were significantly reduced in the orlistat group (8 cases out of 153 subjects) versus placebo (17 cases out of 156 subjects) (P = 0.041). CONCLUSIONS: The addition of orlistat to lifestyle intervention was associated with maintenance of an extra 2.4 kg weight loss after VLED for up to 3 years in obese subjects. The combination of orlistat and lifestyle intervention was associated with a reduced occurrence of type 2 diabetes.     

Dapagliflozin combination therapy in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a progressive disease, and most patients ultimately require two or more antidiabetes drugs in addition to lifestyle changes to achieve and maintain glycemic control. Current consensus statements and guidelines recommend metformin as first-line pharmacotherapy for the treatment of T2DM in most patients. When glycemic control cannot be maintained with metformin alone, the sequential, stepwise addition of other agents is recommended. Agents such as thiazolidinediones or sulfonylureas have typically been added to metformin therapy. Although effective in reducing glycated hemoglobin, these drugs are often associated with adverse effects, most notably weight gain, and in the case of sulfonylureas, hypoglycemia. Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, are the newest class of antidiabetes drugs approved for the treatment of T2DM. Dapagliflozin effectively improves glycemic control by increasing the renal excretion of excess glucose. In clinical trials, dapagliflozin has been well tolerated and has additional benefits of weight loss, low risk of hypoglycemia and reduction in blood pressure. This review discusses the clinical evidence and rationale for the use of dapagliflozin as add-on therapy in T2DM. The results suggest that dapagliflozin add-on therapy is a promising new treatment option for a wide range of patients with T2DM. Results from an ongoing cardiovascular outcomes trial are needed to establish the long-term safety of dapagliflozin.     

新诊断的肥胖和非肥胖2型糖尿病患者的临床比较研究

【目的】提高对2型糖尿病（T2DM）肥胖患者代谢紊乱的认识。【方法】81例新诊断的T2DM患者根据体质指数（BMI）分为肥胖和非肥胖两组。肥胖组40例．非肥胖组41例。检测两组的腰围、臀围、血压、空腹血糖（FPG）、餐后2h血糖（2hPG）、空腹C肽（FCP）、餐后2hC肽（2hCP）、血清谷丙转氨酶（GPT）、肾功能、糖化血红蛋白（HbAlC）、血脂全套以及心电图和腹部B超。并进行比较分析。【结果】肥胖组的BMI、腰／臀比、血尿酸、FCP和2hPCP明显高于非肥胖组（P〈0．01）,肥胖组收缩压、舒张压和血清谷丙转氨酶较非肥胖组略高（P〉0．05）,肥胖组中合并中心性肥胖、高血压、高脂血症和非酒精性脂肪肝者比例显著高于非肥胖组（P〈0．01）。【结论】新诊断的T2DM患者中．肥胖患者较非肥胖患者有更严重的代谢紊乱．对肥胖的T2DM患者应采取综合治疗,不仅要控制血糖。还要减肥和减轻胰岛素抵抗。     

Schizophrenia, obesity, and antipsychotic medications: what can we do?

Obesity is one of the most common physical health problems among patients with severe and persistent mental illnesses, such as schizophrenia. Multifactorial in origin, obesity can be attributed to an unhealthy lifestyle as well as the effects of psychotropic medications such as second-generation antipsychotics. Excess body weight increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, hypertension, and gallbladder disease. A PubMed search revealed 403 English-language citations to the query "schizophrenia" AND "obesity" and 469 citations to the query "obesity" AND "antipsychotics." The evidence is that different antipsychotics have different propensities for weight gain, and that children, adolescents, and fi rst-episode patients are at higher risk for weight gain associated with antipsychotic treatment. Monitoring body weight early in treatment will help predict those at high risk for substantial weight gain. Switching antipsychotic medication may or may not be clinically feasible, but can lead to a reduction in body weight. Lifestyle therapies and other nonpharmacological interventions have been shown to be effective in controlled clinical trials, but the evidence base for adjunctive medication strategies such as with orlistat, sibutramine, amantadine, nizatidine, metformin, topiramate, and others, is confl icting. At the very least, a "small-steps approach" to managing weight should be offered to all patients who are overweight or obese.     

Dyslipidemia and glucose dysregulation in overweight and obese patients

Inactivity and a sedentary lifestyle contribute to overweight, obesity, and cardiometabolic risk. Overweight and obesity can lead to metabolic abnormalities, insulin resistance, type 2 diabetes mellitus (DM), lipid disorders, and cardiovascular disease. Diet and exercise can effectively reverse overweight and obesity and their related comorbidities. Modest weight loss (5%-10%) and modest physical activity (30 minutes a day) are first-line recommendations for the prevention of type 2 DM. Clinical trials have demonstrated that insulin sensitivity can be improved and type 2 DM can be prevented through lifestyle modification and pharmacologic therapy, including antiobesity drugs, antidiabetic drugs, statins, and antihypertensive drugs. The endocannabinoid system plays an important role in regulating metabolism through its effects on food intake at the level of the hypothalamus and on body composition through peripheral effects on adipose tissue.     

Treatment of diabetes in patients with severe obesity.

Besides genetic predisposition, obesity is the most important risk factor for the development of diabetes mellitus, and weight reduction has been shown to markedly improve blood glucose control in obese subjects with type 2 diabetes. Therapeutic strategies for the obese diabetic patient include: 1) promoting weight loss through lifestyle modifications (hypocaloric diet and exercise) and anti-obesity drugs (orlistat, sibutramine, etc.); 2) improving blood glucose control, essentially through the reduction of insulin resistance (metformin, eventually thiazolidinediones) or insulin need (alpha-glucosidase inhibitors) and, at a later stage, the correction of defective insulin secretion (sulphonylureas, repaglinide) or low circulating insulin levels (exogenous insulin); and 3) treating common associated risk factors, such as arterial hypertension and dyslipidaemias, to improve cardiovascular prognosis. When morbid obesity is present, both restoring a good glycemic control and correcting associated risk factors can only be obtained through marked and sustained weight loss. This primary objective justifies more aggressive weight reduction programmes, including very low-calorie diets and bariatric surgery, but only within a multidisciplinary approach and in well-selected patients.     

Advanced oxidation protein products (AOPPs) in juvenile overweight and obesity prior to and following weight reduction

Objectives

To evaluate the formation of advanced oxidation protein products (AOPPs) in juvenile overweight/obesity and obesity-related disorders and to investigate the effect of weight reduction on AOPPs.

Design and methods

AOPPs were determined in 114 overweight/obese children and adolescents without/with insulin resistance and metabolic syndrome and compared with 53 lean controls. Measurements were repeated following weight reduction program (diet/exercise, bran-enriched diet/exercise, and diet/exercise plus metformin).

Results

Overweight/obese subjects had higher AOPPs than lean controls, more elevated in patients with co-occurring metabolic syndrome. AOPPs positively correlated with central obesity, triglycerides, lipid peroxidation and insulin, and negatively with glucose to insulin ratio. AOPPs decreased following obesity intervention and ΔAOPPs correlated with ΔBMI%. AOPPs reduction was more pronounced in subjects on bran-enriched diet. Baseline AOPPs were a better predictor of clinically significant weight reduction than BMI%.

Conclusions

Juvenile overweight/obesity was associated with AOPPs accumulation, more pronounced in metabolic syndrome. Body mass reduction decreased oxidative stress, with bran-enriched diet being more effective than diet/exercise alone.     

Lifestyle and Metformin Interventions Have a Durable Effect to Lower CRP and tPA Levels in the Diabetes Prevention Program Except in Those Who Develop Diabetes

OBJECTIVE

We evaluate whether lifestyle and metformin interventions used to prevent diabetes have durable effects on markers of inflammation and coagulation and whether the effects are influenced by the development of diabetes.

RESEARCH DESIGN AND METHODS

The Diabetes Prevention Program was a controlled clinical trial of 3,234 subjects at high risk for diabetes who were randomized to lifestyle, metformin, or placebo interventions for 3.4 years. Diabetes was diagnosed semiannually by fasting glucose and annually by oral glucose tolerance testing. In addition to baseline testing, anthropometry was performed every 6 months; fasting insulin yearly; and hs-CRP, tissue plasminogen activator (tPA), and fibrinogen at 1 year and end of study (EOS).

RESULTS

CRP and tPA levels were unchanged in the placebo group but fell in the lifestyle and metformin groups at 1 year and remained lower at EOS. These reductions were not seen in those who developed diabetes over the course of the study despite intervention. Fibrinogen was lower at 1 year in the lifestyle group. Differences in weight and weight change explained most of the influence of diabetes on the CRP response in the lifestyle group, but only partly in the placebo and metformin groups. Weight, insulin sensitivity, and hyperglycemia differences each accounted for the influence of diabetes on the tPA response.

CONCLUSIONS

Lifestyle and metformin interventions have durable effects to lower hs-CRP and tPA. Incident diabetes prevented these improvements, and this was accounted for by differences in weight, insulin resistance, and glucose levels.     

Lifestyle modification and endothelial function in obese subjects

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-α, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.     

Lifestyle modification and endothelial function in obese subjects

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.     

Recruitment strategies,design, and participant characteristics in a trial of weight-loss and metformin in breast cancer survivors

Weight loss and metformin are hypothesized to improve breast cancer outcomes; however the joint impacts of these treatments have not been investigated.Reach for Health is a randomized trial using a 2 × 2 factorial design to investigate the effects of weight loss and metformin on biomarkers associated with breast cancer prognosis among overweight/obese postmenopausal breast cancer survivors. This paper describes the trial recruitment strategies, design, and baseline sample characteristics.Participants were randomized in equal numbers to (1) placebo, (2) metformin, (3) weight loss intervention and placebo, or (4) weight-loss intervention and metformin. The lifestyle intervention was a personalized, telephone-based program targeting a 7% weight-loss in the intervention arm. The metformin dose was 1500 mg/day. The duration of the intervention was 6 months. Main outcomes were biomarkers representing 3 metabolic systems putatively related to breast cancer mortality: glucoregulation, inflammation, and sex hormones.Between August 2011 and May 2015, we randomized 333 breast cancer survivors. Mass mailings from the California Cancer Registry were the most successful recruitment strategy with over 25,000 letters sent at a cost of $191 per randomized participant. At baseline, higher levels of obesity were significantly associated with worse sleep disturbance and impairment scores, lower levels of physical activity and higher levels of sedentary behavior, hypertension, hypercholesterolemia, and lower quality of life (p < 0.05 for all). These results illustrate the health burden of obesity.Results of this trial will provide mechanistic data on biological pathways and circulating biomarkers associated with lifestyle and pharmacologic interventions to improve breast cancer prognosis.     

Announcements

Abstract

Obesity is one of the most common physical health problems among patients with severe and persistent mental illnesses, such as schizophrenia. Multifactorial in origin, obesity can be attributed to an unhealthy lifestyle as well as the effects of psychotropic medications such as second-generation antipsychotics. Excess body weight increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, hypertension, and gallbladder disease. A PubMed search revealed 403 English-language citations to the query “schizophrenia” AND “obesity” and 469 citations to the query “obesity” AND ''antipsychotics.” The evidence is that different antipsychotics have different propensities for weight gain, and that children, adolescents, and first-episode patients are at higher risk for weight gain associated with antipsychotic treatment. Monitoring body weight early in treatment will help predict those at high risk for substantial weight gain. Switching antipsychotic medication may or may not be clinically feasible, but can lead to a reduction in body weight. Lifestyle therapies and other nonpharmacological interventions have been shown to be effective in controlled clinical trials, but the evidence base for adjunctive medication strategies such as with orlistat, sibutramine, amantadine, nizatidine, metformin, topiramate, and others, is conflicting. At the very least, a “small-steps approach” to managing weight should be offered to all patients who are overweight or obese.