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Semaglutide is a glucagon-like peptide-1 receptor agonist that was recently approved by the US Food and Drug Administration for chronic weight management. This paper reviews data on the mechanism of action, weight-loss and cardiometabolic efficacy, and safety of semaglutide 2.4 mg/week for obesity. Semaglutide has demonstrated the largest weight loss of any obesity medication to date with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risks factors and physical functioning. The approval of this medication provides patients with greater options for weight management.

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

Studies comparing individuals with loss of control (LOC) eating who do and do not have objectively large binge episodes have found that degree of LOC is more important than binge size to psychological and behavioral outcomes. However, the relative importance of these characteristics has not been investigated in a population with binge eating disorder (BED), who by definition all have objectively large binge episodes. Persons with BED and higher weight (N = 34) were enrolled in a BED treatment trial and completed the Loss of Control Over Eating Scale, the Eating Disorder Examination, and measures of eating behavior, mood, and quality of life. Body mass index (BMI) was calculated from measured height and weight. The size of the largest binge episode (measured in kilocalories) and degree of LOC were entered into multiple regression equations to determine their relationships with disordered eating symptoms, depression, quality of life, and BMI in this pilot study. Greater LOC had a stronger independent association than binge size with higher total eating psychopathology, shape dissatisfaction, hunger, food cravings and food addiction symptoms. Larger binge size had a stronger independent association than LOC with higher weight concern and lower general and social quality of life. Both characteristics were associated with higher eating concern and neither were associated with depression or BMI. Both binge size and degree of LOC are associated with important psychosocial treatment targets in patients with BED. Future research should validate the largest binge episode measurement method and replicate the present findings in a larger sample.

The Breast Cancer Weight Loss (BWEL) trial, is a randomized, controlled trial designed to determine whether weight loss after breast cancer diagnosis can reduce the risk of cancer recurrence in women with overweight or obesity. BWEL will compare the efficacy of a telephone-based, weight loss intervention plus health education materials versus health education materials alone on invasive disease-free survival in 3181 women with stage II-III breast cancer and a body mass index (BMI) >27 kg/m(2). In this report, we provide a detailed description of the goals and methods of the lifestyle intervention and the evidence supporting the intervention used in the BWEL trial. The intervention’s primary goal for participants is to achieve and maintain a weight loss of ≥ 10% of baseline weight through increased physical activity and caloric restriction. The evidence supporting the diet, physical activity and behavioral components of this telephone-based weight loss intervention as well as strategies to promote participant engagement and retention are described. The intervention is provided through 42 sessions, delivered by trained health coaches, over a 2-year period. If the BWEL lifestyle intervention is successful in improving cancer outcomes, then weight loss will be incorporated into the care of thousands of breast cancer patients.

OBJECTIVE To evaluate changes in the prevalence of depressive symptoms, loneliness, and insomnia among older adults with type 2 diabetes from 2016 to 2020 and to assess risk factors for these conditions including demographics, multimorbidity, BMI, treatment group, and pre-coronavirus 2019 (COVID-19) measure scores. RESEARCH DESIGN AND METHODS This was a prospective, observational study of participants from the Look AHEAD (Action for Health in Diabetes) cohort study. Data were from two assessments before COVID-19 (visit 1: April 2016–June 2018 and visit 2: February 2018–February 2020) and one assessment during COVID-19 (visit 3: July–December 2020). Surveys were administered to assess depressive symptoms, loneliness, and insomnia. RESULTS The study included 2829 adults (63.2% female, 60.6% White, mean [SD] age 75.6 [6.0] years). The prevalence of mild or greater depressive symptoms did not change significantly between the two pre-pandemic visits (P = 0.88) but increased significantly from pre- to during COVID-19 (19.3% at V2 to 30.4% at V3; P < 0.001). Higher odds of mild or greater depressive symptoms at V3 were associated with being female (adjusted odds ratio [OR] 1.4 [95% CI 1.1–1.7]), identifying as non-Hispanic White (OR 1.4 [95% CI 1.1–1.7]), having obesity (OR 1.3 [95% CI 1.0–1.5]), and reporting mild or greater depressive symptoms at V1 (OR 4.0 [95% CI 2.9–5.4]), V2 (OR 4.4 [95% CI 3.2–5.9]), or both visits (OR 13.4 [95% CI 9.7–18.4]). The prevalence of loneliness increased from 12.3% at V1 to 22.1% at V3 (P < 0.001), while the prevalence of insomnia remained stable across visits at 31.5–33.3%. CONCLUSIONS The prevalence of mild or greater depressive symptoms in older adults with diabetes was more than 1.6 times higher during COVID-19 than before the pandemic.

(1) Examine weight changes in older adults (mean=76 yrs) with type 2 diabetes and overweight/obesity during the COVID-shutdown; (2) Compare the behavioral and psychosocial effects of the shutdown in those who had large weight losses (5%); small weight losses (2-5%), remained weight stable (±2%) or gained weight (2%).Look AHEAD participants (N=2544) were surveyed during the COVID shutdown (2020) and self-reported their current weight, reasons for weight change, weight-related behaviors, psychosocial measures, and negative and positive effects of the pandemic on their lives.Comparing self-reported weight during COVID shutdown to earlier measured weight, Look AHEAD participants lost on average 2.2 kg during the COVID shutdown; 47% lost2% and only 18% gained2%, p.0001. Decreases in physical activity and increases in screen time were reported frequently in all weight change categories. Similarly, there were few differences among the categories on standardized psychosocial measures or self-reported effects of the shutdown on their lives. However, when differences were seen, the most negative impact was in those who gained weight.Although weight loss appeared more common than weight gain during the shutdown, the weight change groups did not differ on most psychosocial and behavioral variables. This article is protected by copyright. All rights reserved.

Losses of 5-10% or more of initial body weight are associated with improvements in obesity-related comorbidities. However, attaining and sustaining this level of weight loss is challenging. The novel anti-obesity medication semaglutide 2.4 mg injected subcutaneously once weekly as an adjunct to a reduced-calorie diet and physical activity helps patients achieve average losses of 9.6-17.4% of initial body weight at week 68, as well as improvements in cardiometabolic and psychosocial indices. Despite these average benefits, prescribers should carefully assess the suitability of patients for this medication. In this paper, we discuss considerations for the selection of individuals who are candidates for semaglutide and special considerations related to the use of this medication. These include its efficacy and safety, as well as its contraindications, potential adverse effects, management of comorbidities and drug interactions, insurance coverage and cost, and patient preferences.

This systematic review synthesized research evaluating the relationship between genetic predictors and weight loss after bariatric surgery. Fifty-seven studies were identified that examined single genes or genetic risk scores. Uncoupling protein (UCP) rs660339 was associated with excess weight loss after surgery in 4 of 6 studies. The most commonly assessed genes were fat mass and obesity–associated (FTO) gene (n = 10) and melanocortin-4 receptor (MC4R) (n = 14). Both were inconsistently related to weight loss. Genetic risk scores predicted weight loss in 6 of 7 studies. This evidence suggests the potential of using genetic variants and genetic risk scores to predict the amount of weight loss anticipated after bariatric surgery and identify patients who may be at risk for suboptimal weight reduction.

Objective The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012. Methods A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured. Results ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg [represented as mean (SE); p = 0.10], respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores. Conclusions Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up.

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).

BACKGROUND: There is growing interest in identifying factors associated with healthy aging. This cross-sectional study evaluated associations of psychological resilience with factors associated with aging in older adults with type 2 diabetes mellitus (T2DM). METHODS: Participants were 3199 adults (72.2 ± 6.2 years of age, 61% female, 61% White, body mass index [BMI] = 34.2 ± 8.2 kg/m(2)) with T2DM enrolled in Look AHEAD (a multi-site randomized clinical trial comparing an intensive lifestyle intervention for weight loss to diabetes education and support). Participants were followed observationally after the 10-year intervention was discontinued. The following items were assessed approximately 14.4 years post-randomization in a cross-sectional analysis: Brief Resilience Scale; overnight hospitalizations in past year; physical functioning measured objectively (gait speed, grip strength) and via self-report (Pepper Assessment Tool for Disability; physical quality of life [QOL; SF-36]); a measure of phenotypic frailty based on having ≥3 of unintentional weight loss, low energy, slow gait, reduced grip strength, and physical inactivity. Depressive symptoms (PHQ-9) and mental QOL (SF-36) were also measured. Logistic/linear/multinomial regression was used to evaluate the association of variables with resilience adjusted for age, race/ethnicity, and gender. RESULTS: Greater psychological resilience was associated with lower BMI, fewer hospitalizations, better physical functioning (i.e., lower self-reported disability, better physical QOL, faster gait speed, greater grip strength, lower likelihood of frailty), fewer depressive symptoms, and greater mental QOL (all p < 0.05). Psychological resilience moderated the relationship of number of hospitalizations in the past year with self-reported disability and grip strength. CONCLUSIONS: Psychological resilience is associated with better physical function and QOL among older adults. Results should be interpreted cautiously given cross-sectional nature of analyses. Exploring the clinical benefits of resilience is consistent with efforts to shift the narrative on aging beyond “loss and decline” to highlight opportunities to facilitate healthy aging.

Internalized weight stigma has gained increasing attention in empirical studies, though questions remain about the adequacy of existing measures. The current study utilized a mixed methods approach, including a novel semi-structured interview, to revisit the conceptualization of internalized weight stigma and explore in more depth the stereotypes and impacts of weight reported by individuals with high scores on the widely-used Weight Bias Internalization Scale. All participants were interviewed as part of the screening procedures for two clinical trials (Study 1 n = 84, mean age=47.8 years, 83.3% women, 67.9% Black, mean BMI=39.2 kg/m

Rationale: Weight loss is recommended to treat obstructive sleep apnea (OSA).Objectives: To determine whether the initial benefit of intensive lifestyle intervention (ILI) for weight loss on OSA se...

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.

OBJECTIVE The aim of this study was to investigate the 6-month nonintervention follow-up effects of a cognitive behavioral intervention for weight bias internalization (WBI; i.e., self-stigma) combined with behavioral weight loss (BWL). METHODS Adults with obesity and elevated WBI were previously randomized to receive BWL alone or in combination with the Weight Bias Internalization and Stigma program (BWL + BIAS). Participants attended weekly group meetings for 12 weeks, followed by two biweekly and two monthly meetings (26 weeks total). Follow-up assessments were conducted at week 52. Changes on the Weight Bias Internalization Scale and Weight Self-Stigma Questionnaire at week 52 were the principal outcomes. Other outcomes included changes in eating, coping, and weight. RESULTS Of 72 randomized participants, 54 (75%) completed week 52 assessments. Linear mixed models showed improvements across groups, but no significant differences between groups, in week 52 change on the Weight Bias Internalization Scale (P = 0.25) or Weight Self-Stigma Questionnaire (P = 0.27). BWL + BIAS participants reported significantly greater benefits than BWL participants on measures of eating and affective coping with weight stigma. Percent weight loss at week 52 did not differ significantly between groups (BWL + BIAS = -3.1% [SE 1.0%], BWL = -4.0% [SE 1.0%], P = 0.53). CONCLUSIONS Reductions in WBI did not differ between groups at 6-month follow-up. Further research is needed to determine the potential benefits of a stigma-reduction intervention beyond BWL.

Objective This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. Methods Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. Results After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). Conclusions An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Background: Weight bias against persons with obesity impairs health care delivery and utilization and contributes to poorer health outcomes. Despite rising rates of pet obesity (including among dogs), the potential for weight bias in veterinary settings has not been examined. Subjects/Methods: In two online, 2×2 experimental studies, the effects of dog and owner body weight on perceptions and treatment recommendations were investigated in 205 practicing veterinarians (Study 1) and 103 veterinary students (Study 2). In both studies, participants were randomly assigned to view one of four vignettes of a dog and owners with varying weight statuses (lean vs. obesity). Dependent measures included emotion/liking ratings toward the dog and owners; perceived causes of the dog’s weight; and treatment recommendations and compliance expectations. Other clinical practices, such as terms to describe excess weight in dogs, were also assessed. Results: Veterinarians and students both reported feeling more blame, frustration, and disgust toward dogs with obesity and their owners than toward lean dogs and their owners (p values

Objective: This study evaluated weight changes after cessation of the 10-year intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study. It was hypothesized that ILI participants would be more likely to gain weight during the 2-year observational period following termination of weight-loss-maintenance counseling than would participants in the diabetes support and education (DSE) control group. Methods: Look AHEAD was a randomized controlled trial that compared the effects of ILI and DSE on cardiovascular morbidity and mortality in participants with overweight/obesity and type 2 diabetes. Look AHEAD was converted to an observational study in September 2012. Results: Two years after the end of the intervention (EOI), ILI and DSE participants lost a mean (SE) of 1.2 (0.2) kg and 1.8 (0.2) kg, respectively (P = 0.003). In addition, 31% of ILI and 23.9% of DSE participants gained ≥ 2% (P < 0.001) of EOI weight, whereas 36.3% and 45.9% of the respective groups lost ≥ 2% of EOI weight (P = 0.001). Two years after the EOI, ILI participants reported greater use of weight-control behaviors than DSE participants. Conclusions: Both groups lost weight during the 2-year follow-up period, but more ILI than DSE participants gained ≥ 2% of EOI weight. Further understanding is needed of factors that affected long-term weight change in both groups.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of disordered eating behaviors including binge eating disorder (BED). Comorbid BED in patients with T2DM has been associated with adverse clinical outcomes such as higher body mass index (BMI) and depressive symptoms. Identifying and addressing this disorder in patients with T2DM is a significant challenge for health-care providers. The purpose of this narrative review is to discuss current perspectives on BED in the context of T2DM with implications for screening and management of these highly comorbid conditions. BED continues to be underrecognized and underdiagnosed. However, there are established tools that providers can use to screen for BED such as the SCOFF Questionnaire and Questionnaire on Eating and Weight Patterns-5. There are several effective treatments for BED including cognitive behavioral therapy, interpersonal therapy, and lisdexamfetamine dimesylate. However, few studies have examined the effects of these treatments in patients with co-morbid T2DM and BED.

Objective. Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight changes during the post-intervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE; control) in individuals with overweight/obesity and type 2 diabetes and sought to identify predictors of excessive post-intervention weight loss and its association with mortality. Research Design and Methods. These secondary analyses compared post-intervention weight change (year-8 to final visit [median 16 years]) in ILI and DSE in 3999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: Weight Gainers (N= 307), Weight Stable (N=1561), Steady Losers (N=1731) and Steep Losers (N=380) on post-intervention mortality, demographic variables and health status at randomization and year-8. Results. Post-intervention weight change averaged -3.7 ±9.5%, with greater weight loss in DSE than ILI. The steep weight loss trajectory subgroup lost on average 17.7 + 6.6%.; 30% of Steep Losers died during post-intervention follow-up vs 10-18% in other trajectories (pBaseline - older; longer diabetes duration; higher BMI; greater multimorbidity; Intervention – randomization to control group; less weight loss in years 1-8; Year 8 - higher prevalence of frailty, multimorbidity and depressive symptoms; lower use of weight control strategies. Conclusion. Steep weight losses post-intervention were associated with increased risk of mortality. Older individuals with longer duration diabetes and multi-morbidity should be monitored for excessive, unintentional weight loss.

This study assessed the relationships between binge eating disorder (BED) and eating self-efficacy in a sample of patients prior to bariatric surgery. The study also examined the extent that BED status accounted for variance in self-efficacy after controlling for demographic factors (age, sex and race), physical variables (comorbidities and body mass index [BMI]) and depressive symptoms. This was a cross-sectional study of pre-surgical data from patients seeking bariatric surgery at a university-based healthcare system (N = 98; mean ± SD age of 46.2 ± 12.5 years; BMI of 45.4 ± 7.2 kg/m

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.

Background. Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5145 individuals with overweight/obesity and type 2 diabetes, found no significant differences in all-cause or cardiovascular mortality or morbidity during 9.6 (median) years of intervention. Participants in ILI who lost ≥10% at 1 year had lower risk of composite cardiovascular outcomes relative to DSE. Objective: Since effects of ILI may take many years to emerge, we conducted intent-to-treat analyses comparing mortality in ILI over 16.7 years (9.6 year of intervention and then observation) to DSE. In a secondary exploratory analysis, we compared mortality by magnitude of weight loss in ILI relative to DSE. Methods. Primary outcome was all-cause mortality from randomization to 16.7 years. Other outcomes included cause-specific mortality, interactions by sub-groups (age, sex, race/ethnicity, CVD history) and an exploratory analysis by magnitude of weight loss in ILI vs DSE as reference. Analyses used proportional hazards regression and likelihood ratio. Results. The incidence of all-cause mortality did not differ significantly in ILI and DSE (549 and 589 participants respectively); HR = 0.91; 95% CI (0.81,1.02), p=0.11. There were no significant differences between treatments in cause-specific mortality or within prespecified subgroups. ILI participants who lost ≥10% at 1 year had a 21% reduced risk of mortality (HR=0.79, CI 0.67,0.94, p=0.007) relative to DSE. Conclusions. ILI focused on weight loss did not significantly affect mortality risk. However, ILI participants who lost ≥10% had reduced mortality relative to DSE.

This study aimed to measure the impact of the COVID-19 pandemic on self-reported life experiences in older adults with diabetes and obesity.Participants were surveyed in 2020 regarding negative and positive impacts of the pandemic across domains of personal, social, and physical experiences. A cumulative negative risk index (a count of all reported negative impacts of 46 items) and a positive risk index (5 items) were characterized in relation to age, sex, race/ethnicity, BMI, and multimorbidity.Response rate was high (2950/3193, 92%), average age was 76 years, 63% were women, and 39% were from underrepresented populations. Women reported more negative impacts than men (6.8 vs. 5.6; p0.001 [of 46 items]) as did persons with a greater multimorbidity index (p0.001). Participants reporting African American/Black race reported fewer negative impacts than White participants. Women also reported more positive impacts than men (1.9 vs. 1.6; p0.001 [of 5 items]).Older adults with diabetes and obesity reported more positive impacts of the pandemic than negative impacts, relative to the number of positive (or negative) items presented. Some subgroups experienced greater negative impacts (e.g., for women, a greater multimorbidity index). Efforts to reestablish personal, social, and physical health after the pandemic could target certain groups.

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

Objective: To evaluate changes in the prevalence of depressive symptoms, loneliness, and insomnia among older adults with type 2 diabetes from 2016 to 2020, and to assess risk factors for these conditions including demographics, multimorbidity, body mass index, treatment group, and pre-COVID-19 measure scores. Research Design and Methods: This was a prospective, observational study of participants from the Look AHEAD cohort study. Data were from two assessments before COVID-19 (Visit 1 (V1): April 2016-June 2018 and Visit 2 (V2): February 2018-February 2020), and one assessment during COVID-19 (Visit 3 (V3): July-December 2020). Surveys were administered to assess depressive symptoms, loneliness, and insomnia. Results: The study included 2829 adults (63.2% female, 60.6% white, mean [SD] age 75.6 [6.0] years). The prevalence of mild or greater depressive symptoms did not change significantly between the two pre-pandemic visits (p=0.88) but increased significantly from pre- to during COVID-19 (19.3% at V2 to 30.4% at V3 (p Conclusions: The prevalence of mild or greater depressive symptoms in older adults with diabetes was more than 1.6 times higher during COVID-19 than before the pandemic.

OBJECTIVE Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. RESEARCH DESIGN AND METHODS These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. RESULTS Postintervention weight change averaged −3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10–18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1–8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. CONCLUSIONS Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.

Objective Previous studies have shown additive weight loss when intensive behavioral therapy (IBT) was combined with weight-loss medication. The present multisite study provides the first evaluation, in primary care, of the effect of the Centers for Medicare and Medicaid Services-based IBT benefit, delivered alone (with placebo) or in combination with liraglutide 3.0 mg. Methods The Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes (SCALE) IBT was a 56-week, randomized, double-blind, placebo-controlled, multicenter trial in individuals with obesity who received liraglutide 3.0 mg (n = 142) or placebo (n = 140) as an adjunct to IBT. Results At week 56, mean weight loss with liraglutide 3.0 mg plus IBT was 7.5% and 4.0% with placebo combined with IBT (estimated treatment difference [95% CI]-3.4% [-5.3% to -1.6%], P = 0.0003). Significantly more individuals on liraglutide 3.0 mg than placebo achieved ≥ 5% weight loss (61.5% vs. 38.8%; odds ratio [OR] 2.5% [1.5% to 4.1%], P = 0.0003), > 10% weight loss (30.5% vs. 19.8%; OR 1.8% [1.0% to 3.1%], P = 0.0469), and > 15% weight loss (18.1% vs. 8.9%; OR 2.3% [1.1% to 4.7%], P = 0.0311). Liraglutide 3.0 mg in combination with IBT was well tolerated, with no new safety signals identified. Conclusions In a primary care setting, Centers for Medicare and Medicaid Services-based IBT produced clinically meaningful weight loss at 56 weeks, enhanced by the addition of liraglutide 3.0 mg.