Corrigendum to "Obesity pillars roundtable: Body mass index and body composition in black and female individuals. Race-relevant or racist? Sex-relevant or sexist?" [Obesity Pillars 4C (2022) 100044].

[This corrects the article DOI: 10.1016/j.obpill.2022.100044.].

Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials.

AIMS: To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning. MATERIALS AND METHODS: The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4). RESULTS: Superiority for semaglutide 2.4 mg over placebo based on IWQOL-Lite-CT and SF-36v2 physical functioning scores was confirmed in STEP 1 and 2 and in STEP 1, 2 and 4, respectively. At Week 68, a greater proportion of participants treated with semaglutide 2.4 mg than with placebo reached meaningful within-person change (MWPC) thresholds for IWQOL-Lite-CT Physical Function scores in STEP 1 (51.8% vs. 28.3%; p < 0.0001) and STEP 2 (39.6% vs. 29.5%; p = 0.0083) and the MWPC threshold for SF-36v2 Physical Functioning in STEP 1 (39.8% vs. 24.1%; p < 0.0001), STEP 2 (41.0% vs. 27.3%; p = 0.0001) and STEP 4 (18.0% vs. 6.6%; p < 0.0001). All other IWQOL-Lite-CT and SF-36v2 scale scores in STEP 1-4 were numerically improved with semaglutide 2.4 mg versus placebo, except for SF-36v2 Role Emotional in STEP 2. CONCLUSIONS: Semaglutide 2.4 mg significantly improved physical functioning, with greater proportions of participants achieving MWPC compared with placebo, and showed beneficial effects on WRQOL and HRQOL beyond physical functioning.

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.

Importance: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. Objective: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. Design, Setting, and Participants: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Interventions: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. Main Outcomes and Measures: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Results: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. Conclusions and Relevance: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. Trial Registration: ClinicalTrials.gov Identifier: NCT04660643.

Review of an international pilot project to adapt the Canadian Adult Obesity Clinical Practice Guideline.

Background: The evidence-based Canadian Adult Obesity Clinical Practice Guideline (CPG) released in August 2020 were developed through a systematic literature review and patient-oriented research process. This CPG is considered a paradigm shift for obesity care as it introduced a new obesity definition that is based on health not body size, incorporates lived experiences of people affected by obesity, and addresses the pervasive weight bias and stigma that patients face in healthcare systems. The purpose of this pilot project was to assess the feasibility of adapting the Canadian CPG in Chile and Ireland. Methods: An International Clinical Practice Guideline Adaptation Committee was established to oversee the project. The project was conducted through four interrelated phases: 1) planning and preparation; 2) pilot project application process; 3) adaptation; and 4) launch, dissemination, and implementation. Ireland used the GRADE-ADAPTE framework and Chile used the GRADE-ADOLOPMENT approach. Results: Chile and Ireland developed their adapted guidelines in one third of the time it took to develop the Canadian guidelines. In Ireland, 18 chapters, which underpin the 80 key recommendations, were contextually adapted. Chile adopted 18 chapters and 76 recommendations, adapted one recommendation, and developed 12 new recommendations.. Conclusion: The pilot project demonstrated it is feasible to adapt the Canadian CPG for use in other countries with different healthcare systems, languages, and cultural contexts, while retaining the Canadian CPG's key principles and values such as the treatment of obesity as a chronic disease, adoption of new clinical assessment approaches that go beyond anthropometric measurements, elimination of weight bias and stigma, shifting obesity care outcomes to improved health and well-being rather than weight loss alone, and the use of patient-centred, collaborative and shared-decision clinical care approaches.

Transforming the landscape of obesity education - The Canadian obesity education competencies.

Background: With ongoing gaps in obesity education delivery for health professions in Canada and around the world, a transformative shift is needed to address and mitigate weight bias and stigma, and foster evidence-based approaches to obesity assessment and care in the clinical setting. Obesity Canada has created evidence-based obesity competencies for medical education that can guide curriculum development, assessment and evaluation and be applied to health professionals' education programs in Canada and across the world. Methods: The Obesity Canada Education Action Team has seventeen members in health professions education and research along with students and patient experts. Through an iterative group consensus process using four guiding principles, key and enabling obesity competencies were created using the 2015 CanMEDS competency framework as its foundation. These principles included the representation of all CanMEDS Roles throughout the competencies, minimizing duplication with the original CanMEDS competencies, ensuring obesity focused content was informed by the 2020 Adult Obesity Clinical Practice Guidelines and the 2019 US Obesity Medication Education Collaborative Competencies, and emphasizing patient-focused language throughout. Results: A total of thirteen key competencies and thirty-seven enabling competencies make up the Canadian Obesity Education Competencies (COECs). Conclusion: The COECs embed evidence-based approaches to obesity care into one of the most widely used competency-based frameworks in the world, CanMEDS. Crucially, these competencies outline how to address and mitigate the damaging effects of weight bias and stigma in educational and clinical settings. Next steps include the creation of milestones and nested Entrustable Professional Activities, a national report card on obesity education for undergraduate medical education in Canada, and Free Open Access Medication Education content, including podcasts and infographics, for easier adoption into curriculum around the world and across the health professions spectrum.

A scoping review of obesity education interventions for current and prospective medical professionals in Canada.

Background: Obesity is a prevalent chronic disease in Canada. Individuals living with obesity frequently interact with medical professionals who must be prepared to provide evidence-based and person-centred care options. The purpose of this scoping review was to summarize existing educational interventions on obesity in Canada for current and prospective medical professionals and to identify key future directions for practice and research. Methods: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. The search strategy was conducted using Medline (via PubMed), Embase, Eric, CBCA, Proquest Education, and Proquest Theses. The inclusion criteria included delivery of an educational intervention on obesity for current medical professionals, medical undergraduate trainees, or residents administered in Canada. Data were extracted from the included studies to thematically summarize the intervention content, and main outcomes assessed. Future directions for research and practice were identified. Results: Eight studies met the inclusion criteria. The interventions ranged in terms of the mode of delivery, including interactive in-person workshops and seminars, online learning modules, webinars, and videos. The main outcomes assessed were attitudes towards patients living with obesity, self-efficacy for having sensitive obesity-related discussions, skills to assess obesity and provision of management options. All studies reported improvements in the outcomes. Future directions identified were the need to develop standardized obesity competencies for inclusion across medical education programs, further research on effective pedagogical approaches to integrating content into existing curricula and the need for broader awareness and assessment of the quality of obesity education resources. Conclusion: Although there have been few obesity-specific educational interventions for current and prospective medical professionals in Canada, existing evidence shows positive learning outcomes. These findings advocate for continued investment in the development of obesity medical training and educational interventions.

A model-based approach to predict individual weight loss with semaglutide in people with overweight or obesity.

AIMS: To determine the relationship between exposure and weight-loss trajectories for the glucagon-like peptide-1 analogue semaglutide for weight management. MATERIALS AND METHODS: Data from one 52-week, phase 2, dose-ranging trial (once-daily subcutaneous semaglutide 0.05-0.4 mg) and two 68-week phase 3 trials (once-weekly subcutaneous semaglutide 2.4 mg) for weight management in people with overweight or obesity with or without type 2 diabetes were used to develop a population pharmacokinetic (PK) model describing semaglutide exposure. An exposure-response model describing weight change was then developed using baseline demographics, glycated haemoglobin and PK data during treatment. The ability of the exposure-response model to predict 1-year weight loss based on weight data collected at baseline and after up to 28 weeks of treatment, was assessed using three independent phase 3 trials. RESULTS: Based on population PK, exposure levels over time consistently explained the weight-loss trajectories across trials and dosing regimens. The exposure-response model had high precision and limited bias for predicting body weight loss at 1 year in independent datasets, with increased precision when data from later time points were included in the prediction. CONCLUSION: An exposure-response model has been established that quantitatively describes the relationship between systemic semaglutide exposure and weight loss and predicts weight-loss trajectories for people with overweight or obesity who are receiving semaglutide doses up to 2.4 mg once weekly.

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity.

BACKGROUND: Obesity is a major risk factor for many leading causes of illness and death worldwide. Data are needed regarding the efficacy and safety of the nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy for weight reduction in adults with obesity. METHODS: In this phase 2, randomized, double-blind trial, we enrolled adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without diabetes. Participants were randomly assigned to receive orforglipron at one of four doses (12, 24, 36, or 45 mg) or placebo once daily for 36 weeks. The percentage change from baseline in body weight was assessed at week 26 (primary end point) and at week 36 (secondary end point). RESULTS: A total of 272 participants underwent randomization. At baseline, the mean body weight was 108.7 kg, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 37.9. At week 26, the mean change from baseline in body weight ranged from -8.6% to -12.6% across the orforglipron dose cohorts and was -2.0% in the placebo group. At week 36, the mean change ranged from -9.4% to -14.7% with orforglipron and was -2.3% with placebo. A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo. The use of orforglipron led to improvement in all prespecified weight-related and cardiometabolic measures. The most common adverse events reported with orforglipron were gastrointestinal events, which were mild to moderate, occurred primarily during dose escalation, and led to discontinuation of orforglipron in 10 to 17% of participants across dose cohorts. The safety profile of orforglipron was consistent with that of the GLP-1 receptor agonist class. CONCLUSIONS: Daily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists. (Funded by Eli Lilly; GZGI ClinicalTrials.gov number, NCT05051579.).

Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison.

AIM: To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. MATERIALS AND METHODS: Using SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points. RESULTS: Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: -4.67% [95% CI -5.91%, -3.43%]; tirzepatide 15 mg mean difference: -5.92% [95% CI -7.16%, -4.68%]; both P < .001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074). CONCLUSIONS: Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.

Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5.

OBJECTIVE: This study evaluated the effect of once-weekly semaglutide 2.4 mg on 2-year control of eating. METHODS: In STEP 5, adults with overweight/obesity were randomized 1:1 to semaglutide 2.4 mg or placebo, plus lifestyle modification, for 104 weeks. A 19-item Control of Eating Questionnaire was administered at weeks 0, 20, 52, and 104 in a subgroup of participants. P values were not controlled for multiplicity. RESULTS: In participants completing the Control of Eating Questionnaire (semaglutide, n = 88; placebo, n = 86), mean body weight changes were -14.8% (semaglutide) and -2.4% (placebo). Scores significantly improved with semaglutide versus placebo for Craving Control and Craving for Savory domains at weeks 20, 52, and 104 (p < 0.01); for Positive Mood and Craving for Sweet domains at weeks 20 and 52 (p < 0.05); and for hunger and fullness at week 20 (p < 0.001). Improvements in craving domain scores were positively correlated with reductions in body weight from baseline to week 104 with semaglutide. At 104 weeks, scores for desire to eat salty and spicy food, cravings for dairy and starchy foods, difficulty in resisting cravings, and control of eating were significantly reduced with semaglutide versus placebo (all p < 0.05). CONCLUSIONS: In adults with overweight/obesity, semaglutide 2.4 mg improved short- and longer-term control of eating associated with substantial weight loss.

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.

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 m-2 and 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 < 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 < 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.

Pharmacotherapy for obesity management

Pharmacological treatments are an effective and scalable approach to treating obesity. As with any chronic disease, such as type 2 diabetes (T2DM) or hypertension, pharmacotherapy is an important pillar in the management of obesity. The focus of obesity management should be the improvement of health parameters (metabolic, mechanical, mental, and/or quality of life [QoL]), not solely weight reduction, and should include outcomes that the patient identifies as important. Obesity is defined by body mass index (BMI) in clinical trials, which itself does not adequately reflect the burden of adiposity-related disease. There are four medications indicated for long-term obesity management in Canada as adjuncts to health-behaviour changes: liraglutide (Saxenda®), naltrexone/bupropion (Contrave®) in a combination tablet, orlistat (Xenical®) and semaglutide (Wegovy®). All four medications are effective in producing clinically significant weight loss and health benefits greater than placebo over a duration of at least one year. The individual response to pharmacotherapy for obesity management is heterogeneous. Efficacy (both for weight and management of obesity-related health issues), mechanism of action, safety, potential side effects/tolerability, contraindications, medication interactions, mode of administration and cost are important considerations in choosing the most appropriate obesity pharmacotherapy. Obesity medications are intended as part of a long-term treatment strategy. Clinical trials of pharmacotherapy for obesity management consistently demonstrate regain of weight when treatment is stopped. Medications that are not approved as pharmacotherapy for obesity management should not be used for this purpose.

Association between weight-loss history and weight loss achieved in clinical obesity management: Retrospective chart review.

OBJECTIVE: Weight history and its association with the weight loss achieved in a publicly funded clinical obesity management program were examined in 9348 patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Tirzepatide Once Weekly for the Treatment of Obesity.

BACKGROUND: Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known. METHODS: In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population. RESULTS: At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively. CONCLUSIONS: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

The i-ACT™ in Obesity educational intervention: a pilot study on improving Canadian family physician care in obesity medicine.

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.