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Background: The STEP 5 trial (NCT03693430) investigated once-weekly (OW) subcutaneous semaglutide 2.4 mg vs placebo for the treatment of overweight/obesity in adults over 2 years. Methods: Adults w ith B MI ≥ 3 0 k g/m2, or ≥27 kg/m2 and ≥ 1 weight-related comorbidity, without diabetes, were randomized 1:1 to semaglutide 2.4 mg OW or placebo for 104 weeks. Co-primary endpoints related to body weight (BW) changes. Control of eating questionnaire (CoEQ) was assessed in a subgroup from Canada/USA, with scores from 19 individual items grouped into 4 domains: craving control, craving for savory, craving for sweet, or positive mood. P values for exploratory CoEQ data are unadjusted for multiplicity.Results: 304 adults were randomized (78% female; mean age 47 years, BW 106.0 kg and BMI 38.5 kg/m2). Semaglutide significantly reduced BW from baseline to week 104 vs placebo (estimated treatment difference: −12.6 %-points [95% CI: –15.3, –9.8]; p < 0.0001). In participants completing the CoEQ with semaglutide (n = 88) vs placebo (n = 86), all 4 domain scores significantly improved at week 20 and 52 (all p < 0.05). At week 104, craving control and craving for savory domains remained significantly improved with semaglutide vs placebo (p < 0.01); positive mood and craving for sweet were not statistically significant. Scores for the following individual craving-related items were significantly reduced from baseline with semaglutide vs placebo at week 104: desire to eat salty and spicy food, craving for dairy food, craving for starchy food, difficulty in resisting cravings, and difficulty in control of eating (all p < 0.05). Scores for hunger and fullness improved with semaglutide vs placebo at week 20, 52 and 104, but the differences were only significant at week 20 (p < 0.001 for both). Conclusions: In adults with overweight/obesity, substantial weight loss with semaglutide 2.4 mg was accompanied by short-and long-term improvements in control of eating vs placebo, with

Background Extended-release naltrexone/bupropion (NB) is indicated for chronic weight management. Incretin agents are recommended for patients with type 2 diabetes. This analysis looked at the add-on of NB to incretins to see if weight loss could occur in patients already stabilized on incretin agents. Methods This was a post-hoc analysis of NB vs. placebo (PL) among subjects with type 2 diabetes stable on an incretin agent prior to randomization in a double-blind, PL-controlled cardiovascular outcome trial (N = 1317). Results Over 1 year, mean weight loss was significantly greater among NB patients vs. PL among those taking DPP-4i (mean absolute difference 4.6% [p p Conclusion NB appears to be effective in reducing weight in patients with T2DM and obesity/overweight who are taking DPP-4ihibitors or GLP-1RA. The SAE rates in all arms of this analysis were lower than have been reported in other cardiovascular outcome trials in type 2 diabetes.

Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).

In the approval process for new weight management therapies, regulators typically require estimates of effect size. Usually, as with other drug evaluations, the placebo-adjusted treatment effect (i.e., the difference between weight losses with pharmacotherapy and placebo, when given as an adjunct to lifestyle intervention) is provided from data in randomized clinical trials (RCTs). At first glance, this may seem appropriate and straightforward. However, weight loss is not a simple direct drug effect, but is also mediated by other factors such as changes in diet and physical activity. Interpreting observed differences between treatment arms in weight management RCTs can be challenging; intercurrent events that occur after treatment initiation may affect the interpretation of results at the end of treatment. Utilizing estimands helps to address these uncertainties and improve transparency in clinical trial reporting by better matching the treatment-effect estimates to the scientific and/or clinical questions of interest. Estimands aim to provide an indication of trial outcomes that might be expected in the same patients under different conditions. This article reviews how intercurrent events during weight management trials can influence placebo-adjusted treatment effects, depending on how they are accounted for and how missing data are handled. The most appropriate method for statistical analysis is also discussed, including assessment of the last observation carried forward approach, and more recent methods, such as multiple imputation and mixed models for repeated measures. The use of each of these approaches, and that of estimands, is discussed in the context of the SCALE phase 3a and 3b RCTs evaluating the effect of liraglutide 3.0 mg for the treatment of obesity.

Weight history and its association with the weight loss achieved in a publicly funded clinical obesity management program were examined in 9348 patients.Weight history (frequency and magnitude of weight losses) was collected through questionnaires at enrollment, and weight change was assessed with retrospective electronic medical chart review.The majority of patients reported developing overweight prior to the age of 40 years and having lost at least 4.5 kg (10 lb) of weight at least once in their lifetime. Those who had an earlier onset of overweight had a higher frequency of past weight loss and had more cumulative weight loss over their lifetime. In women, but not men, earlier age of overweight onset and lifetime weight loss were associated with modestly greater weight loss at the clinic.Women with greater weight-loss history also have modestly greater weight loss at the obesity management clinic. Thus, successful long-term obesity management, particularly for women, may include a series of repeated attempts at weight loss that should not be viewed as failures but could be viewed instead as practice.

Background Obesity is a chronic problem in Canada and although the Canadian Medical Association recognizes obesity as a disease, health care professionals (HCPs) are not necessarily proactively managing it as one. This study aimed to assess current obesity management knowledge and practices of Canadian family physicians (FPs) and evaluate the feasibility of an online self-directed learning platform, i-ACT™ in Obesity, in delivering learning and changing practice intentions to advance obesity management. Methods i-ACT™ in Obesity is an online self-directed learning program designed by Canadian obesity medicine experts to provide individualized learning curricula to participants. One hundred FPs, with an interest in weight management and managing patients with obesity, were recruited across Canada to participate in a pilot study. FP education was delivered in a stepwise manner. Each participant completed a practice profile assessment to determine knowledge gaps and educational needs. Learners then watched didactic videos across disciplines on topics assigned to their curriculum by the program algorithm based on the relative difference between indicated and desired current knowledge. FPs also completed 10 retrospective patient assessments to assess clinical management practices and planned behaviour change. Feasibility, acceptability, and satisfaction of the learning program were assessed to formulate the rationale for a more widespread deployment in the future. Survey responses and related data were analyzed using comparative measures and descriptive statistics. Results The program was piloted by ninety-one Canadian FPs, where 900 patients were assessed. FPs showed distinct differences between their current and desired levels of comfort in a variety of obesity-related topics. Participation was associated with an intention to use more obesity treatment interventions moving forward. The program received an overall satisfaction rating of 8.6 out of 10 and 100% of the evaluators indicated that they would recommend it to their colleagues. Conclusion The program was overall well received and successfully changed obesity management intentions among participating FPs, thus setting the stage for a larger more comprehensive study to examine the efficacy of i-ACT™ in Obesity in addressing knowledge gaps and advancing evidence-based, guidelines-aligned approach to obesity treatment.

POINTS CLES L’obesite est une maladie chronique complexe dans laquelle la graisse corporelle anormale ou excessive (adiposite) nuit a la sante, augmente le risque de complications medicales a long terme et reduit la duree de vie[1][1]. Les etudes epidemiologiques definissent l’obe

KEY POINTS Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.[1][1] Epidemiologic studies define obesity using the body mass index (BMI; weight/height2), which can stratify

Soluble fibre beneficially affects metabolism but whether it can augment the reductions in glycemia induced through intensive weight management has not been extensively studied. Our objective was to examine the adjunct effect of the soluble viscous fibre PGX® on glycemic control in adults with type 2 diabetes (T2D) enrolled in a year-long medically supervised weight management program. In a placebo-controlled, double-blind study, 290 adults with overweight/obesity and T2D were randomized to receive PGX (15–20 g/day) or isocaloric placebo (rice flour, 6.4–8.6 g/day) as an adjunct to intensive weight management for 52 weeks. The primary outcome was change in glycemic control (HbA1c). Other outcome measures included weight loss, blood lipids, blood pressure, cytokines and fecal microbiota. Compared to baseline HbA1c in PGX (7.2 ± 1.1%) and placebo (7.0 ± 0.9%) groups, there was a significant reduction at 16 and 26 weeks, however, only PGX showed a significant absolute reduction of 0.23% at 52 weeks; there were no between-group differences in HbA1c. At 52 weeks, only PGX significantly decreased body weight compared to baseline and reduced waist circumference at all time points. Compared to baseline, only PGX showed a significant reduction in LDL cholesterol at 16 and 26 weeks. PGX significantly increased the relative abundance of Collinsella, Parabacteroides and Roseburia. Adding PGX to a weight management program for individuals with T2D provides a sustained reduction in HbA1c compared to placebo. Improvements in other metabolic outcomes suggest that PGX may be a promising adjunct to weight loss programs in patients with T2D. This trial was registered at ClinicalTrials.gov as NCT01644201.

Summary Objective Liraglutide 3.0 mg is associated with clinically significant weight loss in clinical trials, but real‐world data are lacking. In this analysis, weight loss and persistence outcomes with liraglutide 3.0 mg were assessed across obesity classes, in a real‐world clinical setting. Methods Secondary analysis of an observational, retrospective study of liraglutide 3.0 mg for weight management (as adjunct to diet and exercise) at six Wharton Medical Clinics in Canada. Patients were categorized by body mass index (BMI, kg/m2) into obesity class I (BMI 30–34.9); class II (BMI 35–39.9); and class III (BMI ≥40). Change in weight, categorical weight loss, time to maintenance dose (defined as the time to reach the full liraglutide 3.0 mg maintenance dose) and persistence were assessed for each class and for differences between classes. Results Of 308 patients, 70 (22.7%) had obesity class I, 83 (26.9%) obesity class II and 155 (50.3%) obesity class III. Similar percentage change in weight was observed between obesity classes (mean [standard deviation, SD]: −7.0% [6.0], −6.6% [6.0] and −6.1% [5.0], respectively; p = .640), and similar proportions achieved ≥5% weight loss (60.4%, 62.0% and 55.3%, respectively; p = .717) at 6 months. Mean time to maintenance dose (SD) was 64.2 (56.4) d, 76.4 (56.3) d and 71.4 (54.5) d for obesity classes I, II and III, respectively (p = .509). Persistence with medication was also similar between obesity classes (p = .358). Conclusions These findings suggest that real‐world treatment with liraglutide 3.0 mg, regardless of obesity class, is associated with similar clinically significant weight loss, time to maintenance dose and medication persistence.

The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of ≥5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit). Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0) years, body mass index of 38.5 (6.9) kg msup-2/supand weight of 106.0 (22.0) kg. The mean change in body weight from baseline to week 104 was -15.2% in the semaglutide group (n = 152) versus -2.6% with placebo (n = 152), for an estimated treatment difference of -12.6 %-points (95% confidence interval, -15.3 to -9.8; P lt; 0.0001). More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%; P lt; 0.0001). Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%). In summary, in adults with overweight (with at least one weight-related comorbidity) or obesity, semaglutide treatment led to substantial, sustained weight loss over 104 weeks versus placebo. NCT03693430.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well established in clinical practice for the treatment of type 2 diabetes, and are approved and recommended for weight management in overweight or obesity. Gastrointestinal side effects are well known as the most common adverse effects of these agents and represent a potential barrier for use, particularly at higher doses. Drawing on both published evidence and our collective clinical experience, we aim to guide practitioners through managing these side effects with a view to optimizing therapeutic outcomes with GLP-1RAs.

AIM We evaluated gastrointestinal (GI) adverse events (AEs) with once-weekly semaglutide 2.4 mg in adults with overweight or obesity and their contribution to weight loss (WL). MATERIALS AND METHODS AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262). WL was analysed by presence/absence of GI AEs. Mediation analysis estimated WL effects mediated by and unrelated to GI AEs. GI tolerability with semaglutide 2.4 mg maintenance and cessation after dose escalation was evaluated using STEP 4 data among 803 participants tolerating 20 weeks of semaglutide run-in. RESULTS GI AEs were more common with semaglutide 2.4 mg than placebo, with most frequently nausea (43.9% vs. 16.1% of participants), diarrhoea (29.7% vs. 15.9%), vomiting (24.5% vs. 6.3%) and constipation (24.2% vs. 11.1%). Most GI AEs with semaglutide were non-serious (99.5% of AEs), mild-to-moderate (98.1%), transient and occurred most frequently during/shortly after dose escalation. Few semaglutide-treated participants (4.3%) permanently discontinued treatment for GI AEs. In STEP 1-3, mean WL with semaglutide 2.4 mg was similar in participants without (9.6%-17.1%) versus with GI AEs (11.4%-17.7%). Consistent with this observation, mediation analysis found that GI AEs contributed little to semaglutide-induced WL: of the additional 7.6%-14.4% WL with semaglutide versus placebo

Objective This study aimed to compare weight loss (WL) outcomes for patients taking antidepressants and/or antipsychotics with those not taking psychiatric medication. Methods A total of 17,519 adults enrolled in a lifestyle WL intervention at the Wharton Medical Clinics in Ontario, Canada, were analyzed. Sex-stratified multivariable linear regression analysis was used to examine the association of taking antidepressants, antipsychotics, both, or neither with WL when adjusting for age, initial weight, and treatment time. Results Twenty-three percent of patients were taking at least one psychiatric medication. Patients lost a significant amount of weight (P 0.05). Conversely, men taking antidepressants lost only slightly less weight than men taking both classes or neither class of psychiatric medication (3.2 ± 0.3 kg vs. 5.6 ± 0.9 kg and 4.3 ± 0.1 kg; P 0.05). Conclusions Results of this study suggest that those who participate in a weight management program can lose significant amounts of weight regardless of psychiatric medication use.

Objective To assess changes in weight by calendar month and sex in patients enrolled in a weight loss intervention. Methods Adults participating in a lifestyle weight loss intervention at the Wharton Medical Clinic from January 1st, 2007 to July 4th, 2019 were examined (N = 19,153). A linear generalized estimating equation was used to examine the association between weight change (baseline, month 1, month 2) and calendar month with adjustment for age, sex and baseline body mass index. A first order interaction between sex and calendar was included to assess if the association between calendar month and weight loss differs by sex. Results Patients lost 1.3 ± 2.0 kg (1.2 ± 1.8%) of their body weight per month. As compared to the mean monthly weight loss, patients lost slightly less weight in September (mean, 95% confidence interval (CI): −0.3, −0.4 to −0.2 kg) and slightly more weight in October (0.2, 0.1–0.3 kg). With adjustment for age, body mass index and calendar month, men lost 0.4 kg/month (95% CI: 0.3, 0.5 kg/month) than women. There were no other significant differences in the monthly weight change between men and women (sex*calendar month P-value = 0.24). Conclusion While there were slight differences in the amount of weight change achieved by patients in September, and October, it was not of a magnitude that is likely clinically relevant. In addition, men consistently lost more weight than women across all calendar months. Taken together, this suggest that calendar month is not associated with differences in weight loss for men and women enrolled in a structured weight management program.

OBJECTIVES: Intermittent fasting (IF) is a popular trending diet, yet there is limited evidence-based support considering its clinical impact on cardiometabolic outcomes. In an effort to inform the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we conducted a network meta-analysis of randomized controlled trials (RCTs) comparing IF strategies and continuous energy restriction (CER) on cardiometabolic outcomes using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched through Nov 2020. We included RCTs assessing the effect of IF strategies (alternate-day fasting (ADF), whole-day periodic fasting (WDF), time-restricted feeding (TRF)), CER, and ad libitum diet. Outcomes included body weight, fasting glucose and LDL-cholesterol. Two independent researchers extracted data and assessed risk of bias. A network meta-analysis was performed and data were expressed as mean differences (MD) with 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE. RESULTS: We identified 19 RCTs (n = 590) including adults of varying health backgrounds. ADF and CER both showed a benefit for body weight reduction compared to ad libitum diet (18 trials, n = 520; MD −3.95 kg [95% CI −6.09, −1.81] and MD −2.85 kg [95% CI −4.99, −0.71], respectively). For fasting glucose (17 trials, n = 590), TRF showed a benefit compared to ad libitum diet (MD −0.39 mmol/L [95% CI −0.59, −0.20]), to CER (MD −0.25 mmol/L [95% CI, −0.45 to −0.06]) and to WDF (MD −0.20 mmol/L [95% CI, −0.45, −0.05]). Furthermore, ADF showed a benefit in reducing LDL-cholesterol (17 trials, n = 590) compared to ad libitum diet (MD −0.21 mmol/L [95% CI −0.40, −0.1]), and to CER (MD −0.15 mmol/L [95% CI −0.31, −0.01]). The certainty of the evidence ranged from high to moderate due to variable downgrades for imprecision. CONCLUSIONS: Current evidence provides a good indication that IF strategies have similar benefits to CER for weight loss but may have additional benefits for fasting glucose and LDL-cholesterol. Long-term high quality RCTs are needed to clarify the effect of different IF strategies on cardiometabolic outcomes. FUNDING SOURCES: Diabetes and Nutrition Study Group of the EASD, Canadian Institutes of Health Research (CIHR), Diabetes Canada.

An analysis of the STEP 2 trial evaluated the effect of s.c. semaglutide 2.4 mg vs. placebo (PBO) on physical function (PF) in adults with overweight/obesity and type 2 diabetes (T2D). The STEP 2 trial was an RCT in adults with BMI ≥27 kg/m2 and T2D (NCT03552757). Patients were randomized 1:1:1 to 68 weeks’ once-weekly semaglutide 2.4 mg (N=404), 1.0 mg (N=403; data not shown), or PBO (N=403), plus lifestyle changes. Endpoints included change in PF (baseline-week 68) using the SF-36v2® Health Survey acute version (SF-36) and Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQoL-Lite-CT), and achievement of meaningful within-person PF improvements (≥3.7 points [SF‑36]; ≥14.6 points [IWQoL-Lite-CT]). Patients were 51% female, with a mean age of 55 years, body weight 99.8 kg, and BMI 35.7 kg/m2. Body weight change at week 68 with semaglutide 2.4 mg vs. PBO was -9.6% vs. -3.4%. Semaglutide significantly improved PF vs. PBO on SF-36 and IWQoL‑Lite‑CT (Table). SF-36 and IWQoL-Lite-CT PF improvements correlated with weight loss during the trial. Proportions of patients with clinically meaningful PF improvements were greater with semaglutide vs. PBO (Table). In adults with overweight/obesity and T2D, semaglutide 2.4 mg improved PF vs. PBO, and led to greater proportions of patients with clinically meaningful PF changes in SF-36 and IWQoL-Lite-CT. Disclosure S. Wharton: Advisory Panel; Self; Novo Nordisk A/S, Novo Nordisk Canada Inc., Speaker’s Bureau; Self; AstraZeneca, Bausch Health, Canada, Novo Nordisk, Novo Nordisk Canada Inc. H. H. Meincke: Employee; Self; Novo Nordisk A/S. R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. T. Kalayci oral: Employee; Self; Novo Nordisk A/S. S. Pedersen: Advisory Panel; Self; AstraZeneca, Bausch and Lomb Incorporated, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Global Services, LLC., Novo Nordisk, Consultant; Self; Abbott, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Speaker’s Bureau; Self; Abbott Laboratories, AstraZeneca, Bausch and Lomb Incorporated, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi. D. Rubino: Advisory Panel; Self; Novo Nordisk, Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. D. H. Ryan: Advisory Panel; Self; Alyvent, Naturally Slim, Epitommee,, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Global Services, LLC., Pfizer Inc., Redesign Health, Inc., Sanofi, Consultant; Self; Bausch Health, Canada, Phenomix, Xeno Bioscience, Gila Therapeutics, Scientific Intake, UnitedHealth Group, Other Relationship; Self; Novo Nordisk Inc. N. Zeuthen: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. R. Kolotkin: Consultant; Self; Novo Nordisk, Other Relationship; Self; Rhythm Pharmaceuticals, Inc. Funding Novo Nordisk A/S

Effects of s.c. semaglutide 2.4 mg vs. placebo on health-related quality of life (HRQoL) were evaluated in the STEP 2 trial in adults with overweight/obesity and T2D. The STEP 2 trial was an RCT in adults with BMI ≥27 kg/m2 and T2D (NCT03552757). Patients were randomized 1:1:1 to 68 weeks’ once-weekly semaglutide 2.4 mg (N=404), 1.0 mg (N=403; results not shown), or placebo (N=403), plus lifestyle intervention. Changes in scores at week 68, and achievement of clinically meaningful within-person improvements (see Table for meaningful change thresholds), in weight-related QoL (Impact of Weight on Quality of Life-Lite Clinical Trials Version [IWQoL-Lite-CT]) and HRQoL (SF-36v2® Health Survey acute version [SF-36]) were assessed. Body weight change at week 68 with semaglutide 2.4 mg vs. placebo was -9.6% vs. -3.4%. Changes in IWQoL-Lite-CT scores and SF-36 scores (except role-emotional) were consistently in favor of semaglutide vs. placebo (Table). The proportions of patients with clinically meaningful improvements was greater with semaglutide vs. placebo for all IWQoL-Lite-CT scores and SF-36 physical functioning score (Table). In adults with overweight/obesity and T2D, semaglutide 2.4 mg improved both physical and mental health components vs. placebo and led to greater proportions of patients with clinically meaningful changes in weight-related QoL and physical functioning. Disclosure D. Rubino: Advisory Panel; Self; Novo Nordisk, Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. L. Faerch: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. H. H. Meincke: Employee; Self; Novo Nordisk A/S. R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. S. Pedersen: Advisory Panel; Self; AstraZeneca, Bausch and Lomb Incorporated, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Global Services, LLC., Novo Nordisk, Consultant; Self; Abbott, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Speaker’s Bureau; Self; Abbott Laboratories, AstraZeneca, Bausch and Lomb Incorporated, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi. D. H. Ryan: Advisory Panel; Self; Alyvent, Naturally Slim, Epitommee,, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Global Services, LLC., Pfizer Inc., Redesign Health, Inc., Sanofi, Consultant; Self; Bausch Health, Canada, Phenomix, Xeno Bioscience, Gila Therapeutics, Scientific Intake, UnitedHealth Group, Other Relationship; Self; Novo Nordisk Inc. S. Wharton: Advisory Panel; Self; Novo Nordisk A/S, Novo Nordisk Canada Inc., Speaker’s Bureau; Self; AstraZeneca, Bausch Health, Canada, Novo Nordisk, Novo Nordisk Canada Inc. N. Zeuthen: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. R. Kolotkin: Consultant; Self; Novo Nordisk, Other Relationship; Self; Rhythm Pharmaceuticals, Inc. Funding Novo Nordisk A/S

The weight loss history and weight loss goals were examined in 4108 patients referred to a publicly funded evidence-based clinical weight management program using a retrospective chart review. The majority of patients were white females, aged of 50.1 ± 13.7 years and a BMI of 39.0 ± 7.5 kg/m2 . Pregnancy was the most common reason for weight gain in women (17.7%) and while the reasons in men are more varied (injury, stress and medication: all ~5%). Over 50% of patients cited no specific reason for their weight gain. Self-directed diet and exercise were the most commonly used self-reported weight loss methods. Women were more likely to report using medication and bariatric surgical weight loss methods than men (P

The aims of this study were to assess the effectiveness of a low-carbohydrate high-fat (LCHF) diet with and without a time-restricted feeding (TRF) protocol on weight loss and participating in three sequential dietary interventions (standard calorie-deficit diet, LCHF, and LCHF + TRF) on weight loss outcomes.Data from 227 adults from the Wharton Medical Clinic (WMC) were analyzed using a unidirectional case crossover design. Data was imputed for 154 patients to create a pseudo-sample in which everyone participated in three dietary interventions: standard calorie restriction, LCHF, and LCHF + TRF.Patients lost an average of 11.1 ± 1.3 kg (9.8 ± 1.1%) after three sequential dietary interventions (P0.0001). Patients lost a statistically significant amount of weight from the standard WMC, LCHF, and LCHF+TRF diets (P0.05). With and without adjustment for age, sex, body mass index at the start of the dietary protocol, and treatment time, patients lost a similar amount of weight regardless of the dietary intervention (P0.05). Approximately 78.6% of patients achieved ≥5% weight loss with at least one of the diets.Patients can lose a similar amount of weight regardless of the diet they are following. Approximately 78.9% of patients achieved 5% weight loss with at least one of the diets and lost an average 11.1 kg (or 9.8%). This is nearly double what has been previously reported for one dietary intervention. Thus, participating in sequential diets may be associated with greater absolute weight loss, and likelihood of achieving a clinically significant weight loss.

Objective The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight. Methods Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long-term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight. Results Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%-81.0%), and have a mean BMI of 35.7 to 38.5 kg/m2 and a mean waist circumference of 113.0 to 115.7 cm. Conclusions The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long-term follow-up.

There is significant overlap between obesity and type 2 diabetes (T2DM). Incretin agents (dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs)) are recommended as second-line to metformin in patients with T2DM due to their glucose-lowering effects, low risk of hypoglycemia, and favorable effect on weight. Naltrexone/bupropion (NB) is a combination therapy approved in North America and Europe for chronic weight management. This is an exploratory analysis of the efficacy and safety of NB in T2DM subjects enrolled in two double-blind, placebo-controlled Phase III studies (N=1344), that were stable on an incretin agent prior to randomization. At 1 year, mean weight change was -4.6% ± 0.21% in NB (N=700) compared to -1.1% ± 0.15% in placebo (N=644). In subjects randomized to NB that achieved at ≥5% weight loss at week 16 (early responders, N=269), mean weight change at 1 year was -8.8% ± 0.34%. An analysis of covariance using LOCF adjusting for age, sex, baseline BMI, baseline weight, and responder status revealed no significant interaction between incretin agent and weight treatment medication (p=0.1317), a significant treatment NB vs. placebo effect (p In conclusion, NB is efficacious and safe in reducing weight in patients with obesity and T2DM on DPP-4 inhibitors and GLP-1RAs, and may be an effective addition when weight loss is a focus in treatment. Disclosure S. Wharton: Advisory Panel; Self; Bausch Health Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. P. Yin: Employee; Self; Bausch Health. F. Camacho: Consultant; Self; Bausch + Lomb, Janssen Pharmaceuticals, Inc. M. Burrows: Employee; Self; Bausch Health. J. Blavignac: Employee; Self; Bausch Health Canada. M. Barakat: Employee; Self; Bausch Health.

Background The cause of the obesity epidemic is multifactorial, but may, in part, be related to medication-induced weight gain. While clinicians may strive to do their best to select pharmacotherapy(ies) that has the least negative impact on weight, the literature regarding the weight effects of medication is often limited and devoid of alternative therapies. Results Antipsychotics, antidepressants, antihyperglycemics, antihypertensives and corticosteroids all contain medications that were associated with significant weight gain. However, there are several medication alternatives within the majority of these classes associated with weight neutral or even weight loss effects. Further, while not all of the classes of medication examined in this review have weight-favorable alternatives, there exist many other tools to mitigate weight gain associated with medication use, such as changes in dosing, medication delivery or the use of adjunctive therapies. Conclusion Medication-induced weight gain can be frustrating for both the patient and the clinician. As the use of pharmaceuticals continues to increase, it is pertinent for clinicians to consider the weight effects of medications prior to prescribing or in the course of treatment. In the case where it is not feasible to make changes to medication, adjunctive therapies should be considered.

Background Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss. Methods We did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m 2 or more. We randomly assigned participants (6:1) to each active treatment group (ie, semaglutide [0·05 mg, 0·1 mg, 0·2 mg, 0·3 mg, or 0·4 mg; initiated at 0·05 mg per day and incrementally escalated every 4 weeks] or liraglutide [3·0 mg; initiated at 0·6 mg per day and escalated by 0·6 mg per week]) or matching placebo group (equal injection volume and escalation schedule to active treatment group) using a block size of 56. All treatment doses were delivered once-daily via subcutaneous injections. Participants and investigators were masked to the assigned study treatment but not the target dose. The primary endpoint was percentage weight loss at week 52. The primary analysis was done using intention-to-treat ANCOVA estimation with missing data derived from the placebo pool. This study is registered with ClinicalTrials.gov, number NCT02453711. Findings Between Oct 1, 2015, and Feb 11, 2016, 957 individuals were randomly assigned (102–103 participants per active treatment group and 136 in the pooled placebo group). Mean baseline characteristics included age 47 years, bodyweight 111·5 kg, and BMI 39·3 kg/m 2. Bodyweight data were available for 891 (93%) of 957 participants at week 52. Estimated mean weight loss was −2·3% for the placebo group versus −6·0% (0·05 mg), −8·6% (0·1 mg), −11·6% (0·2 mg), −11·2% (0·3 mg), and −13·8% (0·4 mg) for the semaglutide groups. All semaglutide groups versus placebo were significant (unadjusted p≤0·0010), and remained significant after adjustment for multiple testing (p≤0·0055). Mean bodyweight reductions for 0·2 mg or more of semaglutide versus liraglutide were all significant (−13·8% to −11·2% vs −7·8%). Estimated weight loss of 10% or more occurred in 10% of participants receiving placebo compared with 37–65% receiving 0·1 mg or more of semaglutide (p

Background: Central obesity is associated with increased risk of cardiometabolic disease. Weight loss reduces lean muscle mass, potentially impacting resting energy expenditure and/or physical functioning. This analysis of the STEP 1 trial evaluated the impact of subcutaneous (s.c.) semaglutide, a glucagon-like peptide-1 analogue, on body composition in adults with overweight/obesity using dual energy X-ray absorptiometry (DEXA). Methods: In STEP 1, 1961 adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without diabetes, were randomized to s.c. semaglutide 2.4 mg once-weekly or matched placebo (2:1) for 68 weeks, plus lifestyle intervention. Participants with BMI ≤40 kg/m2 from 9 sites were eligible for the substudy. Total fat mass, total lean body mass and regional visceral fat mass were measured using DEXA at screening and week 68; visceral fat mass was calculated in the L4 region (both males/females), android region (males), or gynoid region (females), depending on site scanner methodology. Proportions of total fat and lean body mass are shown relative to total body mass; proportion of visceral fat mass is expressed relative to region assessed. Results: This analysis included 140 participants (semaglutide n=95; placebo n=45) (mean weight 98.4 kg, BMI 34.8 kg/m2; 76% female). Baseline body composition was similar in those receiving semaglutide and placebo (total fat mass proportion: 43.4% vs 44.6%; regional visceral fat mass proportion: 33.8% vs 36.3%; total lean body mass proportion: 53.9% vs 52.7%; respectively). Percentage change in body weight from baseline to week 68 was -15.0% with semaglutide vs -3.6% with placebo. This resulted in reductions from baseline with semaglutide in total fat mass (-19.3%) and regional visceral fat mass (-27.4%), leading to 3.5%-point and 2.0%-point reductions in the proportions of total fat mass and visceral fat mass, respectively. Total lean body mass decreased from baseline (-9.7%); however, the proportion relative to total body mass increased by 3.0%-points. An increasing improvement in lean body mass:fat mass ratio was seen with semaglutide with increasing weight loss from baseline to week 68 (continuous data). Overall, the ratio increased from baseline (1.34 [95% CI: 1.22, 1.47]) to week 68 by 0.23 [0.14, 0.32], with greater improvement in those with ≥15% weight loss (n=44; 0.41 [0.28, 0.53]) vs Conclusion: In adults with overweight/obesity, semaglutide 2.4 mg was associated with reduced total fat mass and regional visceral fat mass, and an increased proportion of lean body mass. Greater weight loss was associated with greater improvement in body composition (lean body mass:fat mass ratio).

The aim of this study was to examine the associations between baseline and changes in resting metabolic rate (RMR) with chronic condition(s) and weight loss (WL). Sex stratified analysis was undertaken on 393 adults from the Wharton Weight Management Clinics. The association between baseline RMR and WL was examined adjusting for age, BMI, ethnicity and treatment time. The association between changes in RMR (ΔRMR) and WL was also examined adjusting for baseline RMR and above covariates. Models were further adjusted for high glucose, triglycerides, blood pressure, low-density lipoprotein (LDL) and low high-density lipoprotein (HDL). While men (6.0 ± 8.6 kg) and women (5.6 ± 8.3 kg) had significant WL throughout the intervention, their measured decreases in RMR (-48 ± 322 kcal and -5 ± 322 kcal, respectively) were non-significant (P > 0.05). Individuals with a high blood pressure had a higher baseline RMR and women with a high LDL had a lower baseline RMR than those without the chronic condition (P 0.05) in both models. Participants with a low baseline RMR do not appear to be at a disadvantage for WL. Further, WL can occur without decreases in RMR in populations with high levels of obesity and obesity-related comorbidities.

Summary Objective Weight management medications can significantly increase patients' chances of achieving a clinically meaningful weight loss if patients persist with treatment. This retrospective observational study of de‐identified medical records of 311 patients is the first real‐world study examining persistence with liraglutide 3.0 mg in Canada, and also investigates associations between the SaxendaCare® patient support program and persistence and weight loss. Methods Overall persistence was assessed, as well as associations of enrollment in SaxendaCare®, persistence and weight loss. Results Overall mean (standard deviation) persistence with liraglutide 3.0 mg was 6.3 (4.1) months, and 67.5% (n = 210) and 53.7% (n = 167) of patients persisted for ≥4 and ≥ 6 months, respectively. Enrollment in SaxendaCare® was associated with significantly longer persistence with liraglutide 3.0 mg and greater weight loss. Patients enrolled in SaxendaCare® (n = 119) persisted for 7.9 (4.0) versus 5.2 (3.8) months for those not enrolled (n = 184) (p < 0.001), and had significantly greater percent weight loss after 6 months regardless of the duration of their persistence (−7.9% vs −5.5% from baseline, p < 0.01). Conclusions These findings suggest that, in clinical settings, persistence with liraglutide 3.0 mg can exceed 6 months, and that enrolling in SaxendaCare® may be associated with comparatively longer persistence and, regardless of persistence, greater weight loss.

Summary To assess the effectiveness of liraglutide 3.0 mg in post‐bariatric surgery patients, and to determine whether this would differ based on the type of bariatric surgery. One hundred seventeen post‐bariatric surgery patients from the Wharton Medical Clinic were analysed. Changes in weight while taking liraglutide 3.0 mg were examined for all patients, and by three types of bariatric surgery—Roux‐en‐Y gastric bypass, gastric banding and gastric sleeve. Patients primarily underwent Roux‐en‐Y gastric bypass (n = 53, 45.3%) or gastric banding (n = 50, 42.7%). Over 7.6 ± 7.1 months taking liraglutide 3.0 mg, patients lost a statistically significant amount of weight (−6.3 ± 7.7 kg, P .05). This decrease in weight remained significant after 1‐year of taking liraglutide 3.0 mg (P

Objective: To evaluate the evidence published from 2006 to 2016 on the effectiveness and safety of commonly used natural supplements for weight loss in individuals with obesity.Methods: Amazon and Google were searched for names of mono-agent natural supplements marketed for weight loss and a list of the 10 supplements was created. Google Scholar, Pubmed, Science Direct, and the Cochrane Library were searched for articles that met inclusion.Results: At least one article was published on the effectiveness or safety of bitter orange, capsinoid, carnitine, chromium picolinate, Coleus forskohlii, conjugated linoleic acid, glucomannan, green tea and psyllium for weight loss in populations with obesity from 2006 to 2016. There was insufficient evidence to suggest that the natural supplements examined contribute to significant weight loss, with the exception of perhaps glucomannan in the form of PGX. In general, the majority of side-effects reported were minor to moderate, and gastrointestinal-related. However, in some cases extreme side-effects such as liver and kidney failure were observed.Conclusion: Contrary to popular belief, results of this review suggest that the use of natural supplements for weight loss are unlikely to contribute to meaningful weight loss and in some cases may contribute to harm.