Prevalence of Obesity Among Electronic Cigarette and Tobacco Users in the United States: Results from the 2018 Wave of the Behavioral Risk Factor Surveillance System.

Objective: Tobacco use and obesity are leading causes of preventable death in the U.S. E-cigarette use is on the rise; however, obesity prevalence among e-cigarette users is unknown. The present study characterized obesity prevalence among e-cigarette and tobacco users in a national sample of U.S. adults. Method: Data were obtained from the 2018 Behavioral Risk Factor Surveillance System. Approximately 249,726 participants provided data on e-cigarette and tobacco use, height, weight, and demographics, and were categorized as follows: Ever vaped, ever smoked; Ever vaped, never smoked; Never vaped, ever smoked; Never vaped, never smoked. Results: Obesity prevalence (BMI ≥30 kg/m2) differed significantly across groups: 33.0% (ever vaped, ever smoked); 27.7% (ever vaped, never smoked); 33.1% (never vaped, ever smoked); 32.1% (never vaped, never smoked), p < .001. Groups also differed demographically. Logistic regressions adjusted for demographics revealed subjects in the never vaped, ever smoked group were significantly more likely to have obesity relative to those in the never vaped, never smoked group (p < 0.001) with vaping status having no main effect. Secondary analyses using never smokers as the reference found current smokers were less likely to have obesity and former smokers were more likely to have obesity, p < .001. Discussion: The present study is the first to characterize U.S. obesity prevalence among e-cigarette and tobacco users. Obesity prevalence was lower in the ever vaped, never smoked group; however, this finding appears to be attributable to demographic variables. As e-cigarette use becomes more common, future research should examine the development and maintenance of obesity among users.

Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.

Importance: Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management. Objective: To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity. Design, Setting, and Participants: Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without diabetes (N = 338). Interventions: Participants were randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity. Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the 4-week titration. Placebo groups were pooled (n = 85). Main Outcomes and Measures: The primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68. Semaglutide vs liraglutide comparisons were open-label, with active treatment groups double-blinded against matched placebo groups. Comparisons of active treatments vs pooled placebo were supportive secondary end points. Results: Of 338 randomized participants (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean [SD] body weight, 104.5 [23.8] kg; mean [SD] body mass index, 37.5 [6.8]), 319 (94.4%) completed the trial, and 271 (80.2%) completed treatment. The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide (difference, -9.4 percentage points [95% CI, -12.0 to -6.8]; P < .001); weight change with pooled placebo was -1.9%. Participants had significantly greater odds of achieving 10% or more, 15% or more, and 20% or more weight loss with semaglutide vs liraglutide (70.9% of participants vs 25.6% [odds ratio, 6.3 {95% CI, 3.5 to 11.2}], 55.6% vs 12.0% [odds ratio, 7.9 {95% CI, 4.1 to 15.4}], and 38.5% vs 6.0% [odds ratio, 8.2 {95% CI, 3.5 to 19.1}], respectively; all P < .001). Proportions of participants discontinuing treatment for any reason were 13.5% with semaglutide and 27.6% with liraglutide. Gastrointestinal adverse events were reported by 84.1% with semaglutide and 82.7% with liraglutide. Conclusions and Relevance: Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04074161.

Exploring the wider benefits of semaglutide treatment in obesity: insight from the STEP program.

Obesity negatively impacts patients' health-related quality of life (QOL) and is associated with a range of complications such as type 2 diabetes (T2D), cardiovascular disease, and sleep apnea, alongside decreased physical function, mobility, and control of eating. The Semaglutide Treatment Effect in People with obesity (STEP) trials compared once-weekly subcutaneous semaglutide 2.4 mg with placebo in adults with overweight or obesity, with or without T2D. This article reviews the effects of semaglutide 2.4 mg on QOL, control of eating, and body composition. Weight-related QOL was assessed using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT), and health-related QOL was assessed with the 36-item Short Form Health Survey version 2 (SF-36v2®). Control of eating was evaluated using the Control of Eating questionnaire in a subgroup of participants in one trial. Body composition was evaluated via dual-energy x-ray absorptiometry in another trial, in a subgroup of participants with a body mass index of ≤40 kg/m2. All IWQOL-Lite-CT scores (Physical Function, Physical, Psychosocial, and Total Score) improved with semaglutide 2.4 mg significantly more than with placebo. Across the trials, changes in SF-36v2 scores were generally in favor of semaglutide versus placebo. There were significant improvements in all Control of Eating questionnaire domains (craving control, craving for savory, craving for sweet, and positive mood) up to week 52 with semaglutide treatment versus placebo, with improvements in craving control and craving for savory remaining significantly different at week 104. Body composition findings showed that reductions in total fat mass were greater with semaglutide versus placebo. These findings highlight the wider benefits that patients can experience with once-weekly subcutaneous semaglutide 2.4 mg, in addition to weight loss, including improvements in patients' wellbeing and ability to perform daily activities. Taken together, these are important considerations for primary care when incorporating pharmacotherapy for weight management.

Pragmatic Weight Management Program for Patients With Obesity and Heart Failure With Preserved Ejection Fraction.

Background Obesity is associated with heart failure with preserved ejection fraction (HFpEF). Weight loss can improve exercise capacity in HFpEF. However, previously reported methods of weight loss are impractical for widespread clinical implementation. We tested the hypothesis that an intensive lifestyle modification program would lead to relevant weight loss and improvement in functional status in patients with HFpEF and obesity. Methods and Results Patients with ejection fraction >45%, at least 1 objective criteria for HFpEF, and body mass index ≥30 kg/m2 were offered enrollment in an established 15-week weight management program that included weekly visits for counseling, weight checks, and provision of meal replacements. At baseline, 15 weeks, and 26 weeks, Minnesota Living With Heart Failure score, 6-minute walk distance, echocardiography, and laboratory variables were assessed. A total of 41 patients completed the study (mean body mass index, 40.8 kg/m2), 74% of whom lost >5% of their baseline body weight following the 15-week program. At 15 weeks, mean 6-minute walk distance increased from 223 to 281 m (P=0.001) and then decreased to 267 m at 26 weeks. Minnesota Living With Heart Failure score improved from 59.9 to 37.3 at 15 weeks (P<0.001) and 37.06 at 26 weeks. Changes in weight correlated with change in Minnesota Living With Heart Failure score (r=0.452; P=0.000) and 6-minute walk distance (r=-0.388; P<0.001). Conclusions In a diverse population of patients with obesity and HFpEF, clinically relevant weight loss can be achieved with a pragmatic 15-week program. This is associated with significant improvements in quality of life and exercise capacity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02911337.

Pilot evaluation of a personalized commercial program on weight loss, health outcomes, and quality of life.

WW is a validated behavioral weight management program that encourages healthy habits. WW developed a method of personalizing the SmartPoints® budget depending on dietary and lifestyle preferences, and participants were placed into one of three plans as a pilot evaluation of this new program. In this 6-month, single-arm pilot study, participants attended weekly workshops and used an app to monitor eating and physical activity. Baseline and 6-month assessments included weight, waist circumference, blood pressure, energy intake, cravings, happiness, health-related quality of life, hunger, and fullness. Of 145 adults assessed at baseline, 126 (87%) provided follow-up data. Pre-post changes showed significant reductions in body weight (7.39% ± 5.93%), calories consumed (24.79% ± 32.35%) and significant improvements in cravings, happiness, all SF-36 scales and hunger but not in fullness. Greater % weight loss was related to greater improvements in happiness (r = .38, p < .001), general health perceptions (r = .29, p = .001), and health change (r = .31, p = .001), and greater reduction in role limitations due to personal or emotional problems (r = .24, p = .01). Greater % reduction in caloric intake was associated with greater reductions in cravings (r = .23, p = .01), as well as with greater improvements in happiness (r = .23, p = .01), physical functioning (r = .23, p = .01), and general health perceptions (r = .23, p = .01). Participants in this modified program achieved significant weight loss, regardless of dietary plan, as well as improvements in a variety of other physical and psychological constructs. Those who achieved greater reductions in weight also reported greater improvements in cravings, happiness and some quality of life measures.

Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.

Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, Setting, and Participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. Main Outcomes and Measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. Conclusions and Relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03611582.

Changes in weight control behaviors and hedonic hunger in a commercial weight management program adapted for individuals with type 2 diabetes.

BACKGROUND: A WW (formerly Weight Watchers) program adapted for persons with type 2 diabetes mellitus (T2DM) previously was found to be more effective than standard care (SC) intervention for weight loss, improved glycemic control, and weight- and diabetes-related quality of life measures. With data from the same national trial, this study examined whether WW adapted for persons with T2DM also increased engagement in weight control behaviors and decreased hedonic hunger, each of which could contribute to improved diabetes management. INTERVENTION AND METHODS: Individuals with T2DM (n = 563) and overweight or obesity participated in a 12-month, 16-site, randomized trial of WW with diabetes counseling or SC. Hierarchical linear modeling (HLM) evaluated whether 12-month changes in weight control behaviors (Eating Behavior Inventory; EBI) and hedonic hunger (Power of Food Scale; PFS) differed by treatment condition. If a significant treatment effect was found, 12-month changes in EBI/PFS were regressed on 12-month changes in HbA1c and percent weight loss to explore potential treatment differences in these associations. RESULTS: EBI scores increased significantly over the 12-months (p < 0.001), with greater improvements in WW than SC (p < 0.001). PFS decreased significantly in the 12-months (p < 0.001), with no differences between treatment groups (p = 0.15). HLM analyses that followed up on the significant treatment effect for 12-month change in EBI revealed no significant differences by treatment condition for the relationship between change in EBI scores and change in HbA1c (p = 0.14) or percent weight loss (p = 0.32). Across all participants, 12-month improvements in EBI and PFS were related to improved HbA1c (r = 0.22; -0.13, respectively) and greater percent weight loss (r = 0.41; -0.18, respectively) (ps < 0.01). CONCLUSIONS: WW with diabetes counseling produced greater engagement in weight control behaviors in those with T2DM than did SC. Across both groups, improved weight control behaviors and hedonic hunger were related to improved glycemic control and weight loss.

Description, utilisation and results from a telehealth primary care weight management intervention for adults with obesity in South Carolina.

INTRODUCTION: In the US, obesity rates are higher in rural areas than in urban areas. Rural access to treatment of obesity is limited by a lack of qualified clinicians and by transportation and financial barriers. We describe a telemedicine weight management programme, Wellness Connect, developed through a partnership of academic clinicians and rural primary care providers in South Carolina, and present utilisation and weight outcomes from seven patient cohorts. METHODS: Eight bi-weekly sessions were provided via telemedicine videoconferencing for groups of patients at these rural primary care clinics. Protocol-based sessions were led by registered dietitians, exercise physiologists and clinical psychologists at a central urban location. RESULTS: Of 138 patients who started the programme, 62% (N = 86) of patients met the criteria for completion. Completers lost an average of 3.5% (standard deviation (SD) = 3.9%) body weight, which was statistically significant (p < .001) and corresponded with an average loss of 3.8 kg (SD = 4.5 kg). There were no differences in weight change among clinics (p = .972). Overall, patients and providers reported satisfaction with the programme and identified several challenges to sustainability. DISCUSSION: The use of innovative telemedicine interventions continues to be necessary to alleviate barriers to accessing evidence-based services to reduce chronic diseases and decrease obesity rates among rural populations.

Patients' reasons for weight loss and their relations to clinical weight loss outcomes in a comprehensive lifestyle intervention.

OBJECTIVE: Research suggests that individuals seeking weight loss treatment do so for a variety of reasons. Limited work has explored relations of reasons for weight loss to patient characteristics or to weight loss outcomes. The current study examined these relations. METHODS: The sample consisted of 588 patients in a 15-week fee-for-service weight loss programme. Prior to the intervention, patients completed questionnaires including items on reasons for weight loss, demographic characteristics, and a variety of weight-based characteristics. Patients' weight change outcomes were expressed as percent weight loss and also categorized into one of three previously described weight loss trajectories. RESULTS: The results of chi-squared and t-test analyses suggested that endorsement of health concerns, mobility concerns, or another person's recommendation was associated with higher body mass index (BMI) and older age. These reasons were more likely to be endorsed by White patients than Black patients and by male patients than female patients. Endorsement of doctor recommendation was more likely to be seen among Black patients than White patients. There was no significant relation of any weight loss reason with weight loss outcome. CONCLUSIONS: While certain reasons for weight loss were more often cited by certain patient groups, no specific reason predicted a better or worse outcome.

Body Weight Considerations in the Management of Type 2 Diabetes.

Obesity is one of the main risk factors for type 2 diabetes (T2D), representing a major worldwide health crisis. Modest weight-loss (≥ 5% but < 10%) can minimize and reduce diabetes-associated complications, and significant weight-loss can potentially resolve disease. Treatment guidelines recommend that intensive lifestyle interventions, pharmacologic therapy, and/or metabolic surgery be considered as options for patients with T2D and obesity. The benefits and risks of such interventions should be evaluated in the context of their weight-loss potential, ability to sustain weight change, side effect profile, and costs. Antihyperglycemia therapies have considerable effects on patient weight, prompting careful consideration of weight-loss or weight-neutral therapies for patients with T2D who also have obesity. Metformin, sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), α-glucosidase inhibitors, and amylin mimetics promote weight-loss. Dipeptidyl peptidase-4 inhibitors and fixed-ratio insulin/GLP-1 RA combination therapies (IDegLira, iGlarLixi) appear to be weight-neutral. Thiazolidinediones, insulin secretagogues (sulfonylureas, meglitinides), and insulins are associated with weight gain. Sulfonylureas are additionally associated with a higher risk of serious hypoglycemia from hyperinsulinemia, making them less suitable for the treatment of patients who are overweight or have obesity. Patients are often overtitrated on basal insulin, resulting in an increased risk of hypoglycemia and weight gain without achieving glycemic goals. Given these observations, the effects of antihyperglycemia agents on weight should be considered when individualizing T2D therapy.Funding: Sanofi US, Inc.

Evaluation of a Lifestyle Change Worksite Weight Management Program Across Multiple Employers and Sites.

OBJECTIVE: The aim of the study was to assess weight loss outcomes among participants (N = 1090) of a weight management program across multiple worksites (N = 10) in a retrospective analysis. METHODS: Weekly classes focused on diet, exercise, and behavior change. One employer provided incentives for weight loss and two incentivized weight loss and class attendance. RESULTS: Mean weight loss (N = 1090; 79.3% female) was -2.9% (SD = 3.0%). Average number of classes attended was 6.87/10 (SD = 2.9) and was significantly correlated with percent weight change (r = -0.46; P < 0.001). Participants incentivized for attendance attended significantly more classes (M = 7.5, SD = 2.8) than did those not so incentivized (M = 6.4, SD = 2.9, P < 0.001), but did not lose more weight (P = 0.24). Participants incentivized for weight loss did not lose significantly more weight than those not so incentivized (P = 0.26). CONCLUSIONS: These data support the effectiveness of this worksite program. Utilizing incentives to promote class attendance may be beneficial for increasing engagement in similar programs.

Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial.

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/m2 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/m2. 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<0·0001 vs placebo). All semaglutide doses were generally well tolerated, with no new safety concerns. The most common adverse events were dose-related gastrointestinal symptoms, primarily nausea, as seen previously with GLP-1 receptor agonists. INTERPRETATION: In combination with dietary and physical activity counselling, semaglutide was well tolerated over 52 weeks and showed clinically relevant weight loss compared with placebo at all doses. FUNDING: Novo Nordisk A/S.

Perceptions of Barriers to Effective Obesity Care: Results from the National ACTION Study.

OBJECTIVE: ACTION (Awareness, Care, and Treatment in Obesity maNagement) examined obesity-related perceptions, attitudes, and behaviors among people with obesity (PwO), health care providers (HCPs), and employer representatives (ERs). METHODS: A total of 3,008 adult PwO (BMI ≥ 30 by self-reported height and weight), 606 HCPs, and 153 ERs completed surveys in a cross-sectional design. RESULTS: Despite several weight loss (WL) attempts, only 23% of PwO reported 10% WL during the previous 3 years. Many PwO (65%) recognized obesity as a disease, but only 54% worried their weight may affect future health. Most PwO (82%) felt "completely" responsible for WL; 72% of HCPs felt responsible for contributing to WL efforts; few ERs (18%) felt even partially responsible. Only 50% of PwO saw themselves as "obese," and 55% reported receiving a formal diagnosis of obesity. Despite HCPs' reported comfort with weight-related conversations, time constraints deprioritized these efforts. Only 24% of PwO had a scheduled follow-up to initial weight-related conversations. Few PwO (17%) perceived employer-sponsored wellness offerings as helpful in supporting WL. CONCLUSIONS: Although generally perceived as a disease, obesity is not commonly treated as such. Divergence in perceptions and attitudes potentially hinders better management. This study highlights inconsistent understanding of the impact of obesity and need for both self-directed and medical management.

Characteristics of Weight Loss Trajectories in a Comprehensive Lifestyle Intervention.

OBJECTIVE: Focusing on average weight loss (WL) from interventions provides useful efficacy data but masks large variability across patients. In this study, parameters of weight loss trajectories were determined that differentiated individuals during a 15-week clinical lifestyle intervention. METHODS: Patients (n = 595) were in a fee-for-service WL lifestyle program with a partial meal replacement diet and lifestyle change counseling. Parameters used in latent class analyses were percent WL (%WL), weight nadir, number of weekly weight gains, maximum weekly percent weight gain, standard deviation of weekly weight changes, linear slope values, and change in slope. RESULTS: Average %WL was 9.73%. Latent class analyses revealed three groups with considerable overlap in %WL ranges but differing significantly on all trajectory parameters (Ps < 0.001). Group 1 had the most variable and least successful pattern of weight changes. Group 3 had the least variable and most successful pattern of weight changes. Group 2 fell between the others on all parameters. CONCLUSIONS: Emphasis on average WL likely obscures considerable variability in individual courses of weight change. Moreover, patients with similar %WL can have different WL trajectories. Identification of behavioral/physiological characteristics associated with different weight loss trajectories may facilitate the development of more tailored interventions, particularly for trajectories associated with less optimal outcomes.

Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials.

AIMS: Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. METHODS: Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m2 with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/d deficit diet, plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered. RESULTS: In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person-years) and anxiety (1.9 vs 1.7 events/100 person-years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale. CONCLUSIONS: Results of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no between-treatment imbalances in suicidal ideation/behaviour or depression were noted through prospective questionnaire assessments.

Impact on psychosocial outcomes of a nationally available weight management program tailored for individuals with type 2 diabetes: Results of a randomized controlled trial.

AIMS: Type 2 diabetes mellitus (T2DM) can substantially decrease quality of life (QOL). This study examined the effects on QOL-relevant psychosocial measures of a widely available commercial weight loss program enhanced for individuals with T2DM. METHODS: A year-long multi-site randomized clinical trial compared the Weight Watchers (WW) approach, supplemented with phone and email counseling with a certified diabetes educator (CDE), to brief standard diabetes nutrition counseling and education (Standard Care; SC). Participants were 400 women and 163 men (N=279 WW; 284 SC) with T2DM [mean (±SD) HbA1c 8.32±1%; BMI=37.1±5.7kg/m2; age=55.1 ± 9.1years]. Psychosocial outcomes were assessed at baseline, month 6, and month 12 using a diabetes specific psychosocial measure (Diabetes Distress Scale [DDS]), Impact of Weight on Quality of Life-Lite scale (IWQOL), a generic QOL measure (SF-36), and a depression screen (PHQ-9). RESULTS: WW participants showed significantly greater improvements than did SC participants on all DDS subscales and total score and on IWQOL total score and physical function, sex life and work domains (all ps<.05). There was no significant treatment effect on SF-36 scores or PHQ-9. CONCLUSIONS: WW enhanced for individuals with T2DM was superior to SC in improving psychosocial outcomes most specific to T2DM and obesity. Available commercial WL programs, combined with scalable complementary program-specific diabetes counseling, may have benefits that extend to diabetes-related distress and weight-relevant QOL.

Randomized controlled trial of a nationally available weight control program tailored for adults with type 2 diabetes.

OBJECTIVE: Modest weight loss from clinical interventions improves glycemic control in type 2 diabetes (T2DM). Data are sparse on the effects of weight loss via commercial weight loss programs. This study examined the effects on glycemic control and weight loss of the standard Weight Watchers program, combined with telephone and email consultations with a certified diabetes educator (WW), compared with standard diabetes nutrition counseling and education (standard care, SC). METHODS: In a 12-month randomized controlled trial at 16 U.S. research centers, 563 adults with T2DM (HbA1c 7-11%; BMI 27-50 kg/m2 ) were assigned to either the commercially available WW program (regular community meetings, online tools), plus telephone and email counseling from a certified diabetes educator, or to SC (initial in-person diabetes nutrition counseling/education, with follow-up informational materials). RESULTS: Follow-up rate was 86%. Twelve-month HbA1c changes for WW and SC were -0.32 and +0.16, respectively; 24% of WW versus 14% of SC achieved HbA1c <7.0% (P = 0.004). Weight losses were -4.0% for WW and -1.9% for SC (Ps < 0.001). 26% of WW versus 12% of SC reduced diabetes medications (P < 0.001). WW participants had greater reductions in waist circumference (P < 0.001) and C-reactive protein (P = 0.02) but did not differ on other cardiovascular risk factors. CONCLUSIONS: Widely available commercial weight loss programs with community and online components, combined with scalable complementary diabetes education, may represent accessible and effective components of management plans for adults with overweight/obesity and T2DM.

Early Weight Loss with Liraglutide 3.0 mg Predicts 1-Year Weight Loss and is Associated with Improvements in Clinical Markers.

OBJECTIVE: To identify an early response criterion for predicting ≥5% weight loss with liraglutide 3.0 mg at week 56 and to compare efficacy outcomes in early responders (ERs) and early nonresponders (ENRs). METHODS: Using pooled data from the SCALE Obesity and Prediabetes and SCALE Diabetes trials, weight loss of ≥4% at 16 weeks best predicted ≥5% weight loss after 56 weeks. Weight loss and changes in cardiometabolic risk factors and health-related quality of life were evaluated in ERs (≥4% weight loss at week 16) and ENRs (<4% weight loss at week 16) completing 56 weeks' treatment. RESULTS: Proportions of ERs/ENRs to liraglutide 3.0 mg were 77.3%/22.7% (individuals without type 2 diabetes, T2D) and 62.7%/37.3% (those with T2D). Greater mean weight loss was observed in ERs versus ENRs: 10.8% versus 3.0% (without T2D) and 8.5% versus 3.1% (T2D). In both trials, greater proportions of ERs versus ENRs achieved ≥5%, >10%, and >15% weight loss at week 56 with liraglutide 3.0 mg. Greater improvements in cardiometabolic risk factors and health-related quality of life scores were observed in ERs versus ENRs. CONCLUSIONS: The early response criterion was clinically useful to identify individuals who would achieve clinically meaningful weight loss at 56 weeks.