Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. Safety was also assessed. RESULTS: A total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo. The mean (±SD) duration of exposure to semaglutide or placebo was 34.2±13.7 months, and the mean duration of follow-up was 39.8±9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001). CONCLUSIONS: In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 months. (Funded by Novo Nordisk; SELECT ClinicalTrials.gov number, NCT03574597.).

Drugs for Treating Obesity.

Older medications approved for chronic weight management (orlistat, naltrexone/bupropion, liraglutide 3 mg and, in the USA, phentermine/topiramate) have not been widely adopted by health care providers. Those medications produce only modest additional weight loss when used to augment lifestyle intervention. However, semaglutide 2.4 mg weekly has recently emerged and produces much more weight loss - on average 15% weight loss at 1 year. Semaglutide's enhanced efficacy and that its class (GLP-1 receptor analogs) is well-known may result in more clinicians adopting pharmacotherapy. Furthermore, the first dedicated cardiovascular outcome trial powered for superiority testing an anti-obesity medication (SELECT) is underway with semaglutide 2.4 mg. A positive outcome will further promote the concept that weight management should be a primary target for cardiometabolic disease control. In phase 3, tirzepatide and cagrilintide/semaglutide combination are showing promise for even greater weight loss efficacy. Another recently approved medication takes a personalized medicine approach; setmelanotide is approved as a therapy for those with some of the ultra-rare genetic diseases characterized by severe, early onset obesity. This chapter reviews the currently available and anticipated medications for chronic weight management as well as those approved for the genetic and syndromic obesities.

Improving Quality Outcomes: The Value of Diabetes Care and Education Specialists.

Given the growing prevalence and accelerating cost of diabetes, there is an urgent need to expand strategies in health care that improve access and outcomes and reduce the financial and human burden of the disease. Diabetes care and education specialists (DCESs) are well positioned to assist health care systems with delivery models that enhance diabetes care through evidence-based standards and quality improvement strategies. DCESs have increased opportunities to apply their competencies in primary, specialty, hospital, and acute care settings; accountable care organizations; community settings; research; and academia. Two national certification programs provide an evidence-based foundation for quality in the specialty, with updated competencies guiding practice. This article serves as a call to action for health care systems to integrate specialists in diabetes care and education into diabetes care delivery models and raise awareness of the positive impact these professionals have on the lives of people with diabetes.

Evidence-based weight loss interventions: Individualized treatment options to maximize patient outcomes.

Against the backdrop of obesity as a major public health problem, we examined three questions: How much weight loss is needed to benefit patients with obesity? How well do current therapies do in producing weight loss? What strategies can be used to improve patient outcomes using evidence-based studies. This paper reviews literature on the outcomes of lifestyle, diet, medications and surgical treatments for obesity using literature searches for obesity treatments. Current treatments, including lifestyle, diet and exercise, produce a weight loss of 5% to 7% on average. Despite continued attempts to identify superior dietary approaches, most careful comparisons find that low carbohydrate diets are not significantly better than low fat diets for weight loss. The four medications currently approved by the US Food and Drug Administration for long-term management of obesity are not as effective as surgery, adding about 5% on average to lifestyle approaches to weight loss. Two new medications that are under investigation, semaglutide and tirzepatide, significantly improve on this. For all treatments for weight loss, including lifestyle, medications and surgery, there is enormous variability in the amount of weight lost. Examination of this literature has yielded evidence supporting baseline and process predictors, but the effect sizes associated with these predictors are small and there are no prospective studies showing that a personalized approach based on genotype or phenotype will yield uniform success. Because obesity is a chronic disease it requires a 'continuous treatment model' across the lifespan.

Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity.

Energy Balance and Weight Loss for Diabetes Remission.

Diabetes remission-the occurrence of durable normoglycemia without antidiabetic medications-has been demonstrated in some patients with type 2 diabetes who have achieved and sustained weight loss through lifestyle intervention or metabolic and bariatric surgery. Although this pursuit would represent a paradigm shift in our diabetes chronic care model, could diabetes remission become a routine treatment strategy in patients with type 2 diabetes? This article reviews the mechanisms by which weight loss can drive improvements in insulin sensitivity and ß-cell function sufficient to normalize glycemia, treatment approaches that provide evidence for diabetes remission, and avenues for developing the research and discovery that will be required to make diabetes remission possible as part of the routine medical management of type 2 diabetes.

Fiber Intake Predicts Weight Loss and Dietary Adherence in Adults Consuming Calorie-Restricted Diets: The POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) Study.

BACKGROUND: The effects of dietary composition on weight loss are incompletely understood. In addition to energy intake, fiber intake, energy density, macronutrient composition, and demographic characteristics have all been suggested to contribute to weight loss. OBJECTIVE: The primary aim of this analysis was to assess the role of dietary fiber as a predictor of weight loss in participants who consumed calorie-restricted diets (-750 kcal/d from estimated energy needs) for 6 mo, using data from the POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) Study-a randomized trial that examined the effects of calorie-restricted diets varying in macronutrient composition on weight loss in adults. METHODS: Data were randomly partitioned to a training data set (70%) in which the effects of fiber and other weight-loss predictors were identified using adjusted Least Absolute Shrinkage and Selection Operator and model averaging. The retained predictors were then fit on the testing data set to assess predictive performance. RESULTS: Three hundred and forty-five participants (53.9% female) provided dietary records at baseline and 6 mo. Mean ± SD age and BMI for the full sample was 52.5 ± 8.7 y and 32.6 ± 3.9 kg/m2, respectively. Mean ± SD (99% CI) weight change at 6 mo for the full sample was -7.27 ± 5.6 kg (-8.05, -6.48 kg). The final, best fit model (R2 = 0.41) included fiber, energy density, fat, age, adherence, baseline weight, race, and changes from baseline in carbohydrate, fiber, PUFA, and MUFA intake, but the most influential predictor was fiber intake ($\hat{\beta }$ = -0.37; P < 0.0001). In addition, fiber was strongly associated with adherence to the macronutrient prescriptions (P < 0.0001). Interactions between race and adherence, age, baseline weight, carbohydrate, energy density, and MUFAs were also retained in the final model. CONCLUSION: Dietary fiber intake, independently of macronutrient and caloric intake, promotes weight loss and dietary adherence in adults with overweight or obesity consuming a calorie-restricted diet. This trial was registered at clinicaltrials.gov as NCT00072995.

Management of obesity.

A modern approach to obesity acknowledges the multifactorial determinants of weight gain and the health benefits to be derived from weight loss. Foundational to any weight loss effort is lifestyle change, diet, and increased physical activity. The approach should be a high quality diet to which patients will adhere accompanied by an exercise prescription describing frequency, intensity, type, and time with a minimum of 150 min moderate weekly activity. For patients who struggle with weight loss and who would receive health benefit from weight loss, management of medications that are contributing to weight gain and use of approved medications for chronic weight management along with lifestyle changes are appropriate. Medications approved in the USA or European Union are orlistat, naltrexone/bupropion, and liraglutide; in the USA, lorcaserin and phentermine/topiramate are also available. Surgical management (gastric banding, sleeve gastrectomy, and Roux-en Y gastric bypass) can produce remarkable health improvement and reduce mortality for patients with severe obesity.

Neonatal Nurses NICU Quality Improvement: Embracing EBP Recommendations to Provide Parent Psychosocial Support.

BACKGROUND: The neonatal intensive care unit (NICU) can be a stressful environment for infants, their families, and the healthcare team. There is an immediate need for neonatal nurses to embrace and translate the new National Perinatal Association recommendations for psychosocial support of NICU parents into clinical practice to demonstrate best practices for infants, their families, and the whole team. PURPOSE: To summarize the current evidence-based practice recommendations and to provide suggestions for team members to develop strategies to adopt and implement them through quality improvement (QI) projects. METHODS: Literature reviews were conducted by the original 6 National Perinatal Association workgroup teams and covered all levels of available evidence (eg, qualitative, quantitative, and clinical research, guidelines, and clinical and parental expertise). Evidence was synthesized to formulate this set of recommendations published in December 2015. We describe their applicability to the vital role of neonatal nurses, while elucidating QI projects that track measurements of change to translate these recommendations into practice. RESULTS: Neonatal nurses are in an ideal position to transform systems of support for NICU parents through the adoption of these recommendations at the bedside, and further to identify areas for QI to enhance implementation. IMPLICATIONS FOR PRACTICE: Neonatal nurses are integral to problem solving and identifying QI strategies for translating these recommendations into NICU clinical practice to improve parent psychosocial support. IMPLICATIONS FOR RESEARCH: This article disseminates evidence and encourages scientific investigation into various methods of supporting emotional health of NICU parents to create better health outcomes.

Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.

BACKGROUND: Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients. METHODS: In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years. RESULTS: The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51). CONCLUSIONS: An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).

Body mass index and the risk of all-cause mortality among patients with type 2 diabetes mellitus.

BACKGROUND: Several prospective studies have evaluated the association between body mass index (BMI) and death risk among patients with diabetes mellitus; however, the results have been inconsistent. METHODS AND RESULTS: We performed a prospective cohort study of 19 478 black and 15 354 white patients with type 2 diabetes mellitus. Cox proportional hazards regression models were used to estimate the association of different levels of BMI stratification with all-cause mortality. During a mean follow-up of 8.7 years, 4042 deaths were identified. The multivariable-adjusted (age, sex, smoking, income, and type of insurance) hazard ratios for all-cause mortality associated with BMI levels (18.5-22.9, 23-24.9, 25-29.9, 30-34.9 [reference group], 35-39.9, and ≥40 kg/m(2)) at baseline were 2.12 (95% confidence interval [CI], 1.80-2.49), 1.74 (95% CI, 1.46-2.07), 1.23 (95% CI, 1.08-1.41), 1.00, 1.19 (95% CI, 1.03-1.39), and 1.23 (95% CI, 1.05-1.43) for blacks and 1.70 (95% CI, 1.42-2.04), 1.51 (95% CI, 1.27-1.80), 1.07 (95% CI, 0.94-1.21), 1.00, 1.07 (95% CI, 0.93-1.23), and 1.20 (95% CI, 1.05-1.38) for whites, respectively. When stratified by age, smoking status, patient type, or the use of antidiabetic drugs, a U-shaped association was still present. When BMI was included in the Cox model as a time-dependent variable, the U-shaped association of BMI with all-cause mortality risk did not change. CONCLUSIONS: The present study indicated a U-shaped association of BMI with all-cause mortality risk among black and white patients with type 2 diabetes mellitus. A significantly increased risk of all-cause mortality was observed among blacks with BMI <30 kg/m(2) and ≥35 kg/m(2) and among whites with BMI <25 kg/m(2) and ≥40 kg/m(2) compared with patients with BMI of 30 to 34.9 kg/m(2).

Dietary Fat Intake Modifies the Effect of a Common Variant in the LIPC Gene on Changes in Serum Lipid Concentrations during a Long-Term Weight-Loss Intervention Trial.

BACKGROUND: Hepatic lipase (HL) plays a pivotal role in the metabolism of HDL and LDL. Recent genome-wide association studies have identified common variants in the HL gene (LIPC) associated with HDL cholesterol. OBJECTIVE: We tested the effect of a common variant in LIPC on changes in blood lipids in response to weight-loss diets in the Preventing Overweight Using Novel Dietary Strategies Trial. METHODS: We genotyped LIPC rs2070895 in 743 overweight or obese adults aged 30-70 y (61% women) who were assigned to high-fat (40% energy) or low-fat (20% energy) diets for 2 y. We measured serum concentrations of total cholesterol (TC), triglycerides, LDL cholesterol, and HDL cholesterol at baseline and 2 y of intervention. RESULTS: At 2 y of intervention, dietary fat modified effects of the variant on changes in serum TC, LDL cholesterol, and HDL cholesterol (P-interaction: 0.0008, 0.004, and 0.03, respectively). In the low-fat group, as compared to the G allele, the A allele tended to be related to the decrease in TC and LDL cholesterol concentrations [TC (ß ± SE): -5.5 ± 3.0, P = 0.07; LDL cholesterol: -4.8 ± 2.5, P = 0.06] and a lower increase in HDL cholesterol concentrations (ß ± SE: -1.37 ± 0.69, P = 0.048), whereas an opposite effect in the high-fat diet group was evident [TC (ß ± SE): 7.3 ± 2.7, P = 0.008; LDL cholesterol: 4.1 ± 2.3, P = 0.07], and there was no genetic effect on changes in HDL cholesterol concentrations (P = 0.54). CONCLUSION: Dietary fat intake modifies the effect of a common variant in LIPC on changes in serum lipids during a long-term weight-loss intervention in overweight or obese adults. This trial was registered at clinicaltrials.gov as NCT00072995.

The Mealtime Challenge: Nutrition and Glycemic Control in the Hospital.

In Brief Multiple staff members and departments have a responsibility for various aspects of nutrition therapy for glycemic management in the hospital setting. Implementation is initiated by physicians, nurse practitioners, and physician's assistants and planned and operationalized by registered dietitians. Meals are delivered by food service staff, and nurses monitor and integrate glycemic control components into patients' medical treatment plan. Although nutrition therapy is recognized as an important aspect of care in the hospital setting, it can also be challenging to appropriately coordinate meals with blood glucose monitoring and insulin administration. This article addresses current mealtime practices and recommendations to improve these processes in acute care.

Screening for critical congenital heart disease in newborns using pulse oximetry: evaluation of nurses' knowledge and adherence.

PURPOSE: The purpose of this project was to evaluate the benefits of an online nursing education program addressing the significance and rationale of an evidence-based critical congenital heart disease (CCHD) screening protocol using pulse oximetry implemented on full-term newborns delivered at an academic obstetric referral center. The aim was to assess nurses' knowledge of the protocol and nurses' adherence to the protocol documentation before and after the education module was implemented. SUBJECTS: Registered nurses working in the birthing center who completed the online knowledge tests and an education module. DESIGN: A repeated-measures quality improvement study was conducted to assess nurses' knowledge of the evidence supporting CCHD screening by pulse oximetry and adherence to the correct documentation of the screening protocol before, immediately after, and 3 months following participation in an online education module. METHODS: Nurses' knowledge of the CCHD screening protocol was determined by the number of correct answers on a 10-item online test administered before and after the education module. Adherence to correct documentation of the protocol before and after the education intervention was evaluated. The medical charts of 300 newborns delivered at the center with pulse oximetry readings performed after 24 hours of age and before discharge were randomly selected and reviewed. RESULTS: A significant improvement in knowledge test scores was observed immediately after the education module (9.1 ± 1.0), relative to baseline (8.4 ± 1.2; paired t = 3.02, P = .0046). A significant increase in knowledge test scores measured at baseline, immediately after, and 3 months postintervention was also indicated (F = 3.25; df = 2, 24; P = .0564). Documentation of the protocol in the medical charts for the location of the readings significantly improved after the educational intervention (right hand: 28%, 83%, and 90%; right foot: 27%, 82%, and 89%; both P < .0001). CONCLUSIONS: Providing education to staff before implementing new practice changes enhances their knowledge. Quality improvement monitoring is recommended to ensure nursing adherence to any practice change.

Assessment and lifestyle management of patients with obesity: clinical recommendations from systematic reviews.

IMPORTANCE: Even though one-third of US adults are obese, identification and treatment rates for obesity remain low. Clinician engagement is vital to provide guidance and assistance to patients who are overweight or obese to address the underlying cause of many chronic diseases. OBJECTIVES: To describe current best practices for assessment and lifestyle management of obesity and to demonstrate how the updated Guidelines (2013) for Managing Overweight and Obesity in Adults based on a systematic evidence review sponsored by the National Heart, Lung, and Blood Institute (NHLBI) can be applied to an individual patient. EVIDENCE REVIEW: Systematic evidence review conducted for the Guidelines (2013) for Managing Overweight and Obesity in Adults supports treatment recommendations in 5 areas (risk assessment, weight loss benefits, diets for weight loss, comprehensive lifestyle intervention approaches, and bariatric surgery); for areas outside this scope, recommendations are supported by other guidelines (for obesity, 1998 NHLBI-sponsored obesity guidelines and those from the National Center for Health and Clinical Excellence and Canadian and US professional societies such as the American Association of Clinical Endocrinologists and American Society of Bariatric Physicians; for physical activity recommendations, the 2008 Physical Activity Guidelines for Americans); a PubMed search identified recent systematic reviews covering depression and obesity, motivational interviewing for weight management, metabolic adaptation to weight loss, and obesity pharmacotherapy. FINDINGS: The first step in obesity management is to screen all adults for overweight and obesity. A medical history should be obtained assessing for the multiple determinants of obesity, including dietary and physical activity patterns, psychosocial factors, weight-gaining medications, and familial traits. Emphasis on the complications of obesity to identify patients who will benefit the most from treatment is more useful than using body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) alone for treatment decisions. The Guidelines (2013) recommend that clinicians offer patients who would benefit from weight loss (either BMI of ≥30 with or without comorbidities or ≥25 along with 1 comorbidity or risk factor) intensive, multicomponent behavioral intervention. Some clinicians do this within their primary care practices; others refer patients for these services. Weight loss is achieved by creating a negative energy balance through modification of food and physical activity behaviors. The Guidelines (2013) endorse comprehensive lifestyle treatment by intensive intervention. Treatment can be implemented either in a clinician's office or by referral to a registered dietitian or commercial weight loss program. Weight loss of 5% to 10% is the usual goal. It is not necessary for patients to attain a BMI of less than 25 to achieve a health benefit. CONCLUSIONS AND RELEVANCE: Screening and assessment of patients for obesity followed by initiation or referral of treatment should be incorporated into primary care practice settings. If clinicians can identify appropriate patients for weight loss efforts and provide informed advice and assistance on how to achieve and sustain modest weight loss, they will be addressing the underlying driver of many comorbidities and can have a major influence on patients' health status.

Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity but Without Diabetes in SELECT.

OBJECTIVE: To evaluate the cardiovascular effects of semaglutide by baseline glycated hemoglobin (HbA1c) and change in HbA1c in a prespecified analysis of Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT). RESEARCH DESIGN AND METHODS: In SELECT, people with overweight or obesity and atherosclerotic cardiovascular disease without diabetes were randomized to weekly semaglutide 2.4 mg or placebo. The primary end point of first major adverse cardiovascular event (MACE) (cardiovascular mortality, nonfatal myocardial infarction, or stroke) was reduced by 20% with semaglutide versus placebo. Analysis of outcomes included first MACE, its individual components, expanded MACE (cardiovascular mortality, nonfatal myocardial infarction, or stroke; coronary revascularization; or hospitalization for unstable angina), a heart failure composite (heart failure hospitalization or urgent medical visit or cardiovascular mortality), coronary revascularization, and all-cause mortality by baseline HbA1c subgroup and categories of HbA1c change (<-0.3, -0.3 to 0.3, and >0.3 percentage points) from baseline to 20 weeks using the intention-to-treat principle with Cox proportional hazards. RESULTS: Among 17,604 participants (mean age 61.6 years, 72.3% male), baseline HbA1c was <5.7% for 33.5%, 5.7% to <6.0% for 34.6%, and 6.0% to <6.5% for 31.9%. Cardiovascular risk reduction with semaglutide versus placebo was not shown to be different across baseline HbA1c groups and was consistent with that of the overall study for all end points, except all-cause mortality. Cardiovascular outcomes were also consistent across subgroups of HbA1c change. CONCLUSIONS: In people with overweight or obesity and established atherosclerotic cardiovascular disease but not diabetes, semaglutide reduced cardiovascular events irrespective of baseline HbA1c or change in HbA1c. Thus, semaglutide is expected to confer cardiovascular benefits in people with established atherosclerotic cardiovascular disease who are normoglycemic at baseline and/or in those without HbA1c improvements.

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial.

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m-2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597 .