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Introduction: The experience of persons with obesity (PwO) in the Canadian healthcare setting has not been widely studied. The objective of this study was to assess care in PwO in emergency departments in Ontario, Canada. Methods: This secondary analysis made use of 2018–2022 Canadian Institute for Health Information's National Ambulatory Care Reporting System. The sample consisted of 4547 individuals with an obesity diagnosis, and 4547 controls who were matched for sex, age, and main diagnosis. Ordinal logistic and multiple linear regression analyses were used to assess triage scores, wait times, and length of stay. Results: PwO had 4.8 minutes longer wait time for a physician initial assessment (p<0.01), 3.56 hours longer length of stay in the emergency department (p<0.0001), and 55% greater odds (OR = 1.55, 95% CI: 1.43–1.68) of having a less urgent triage score compared to controls matched for main diagnosis. When further matched for triage score, PwO experienced over three hours longer length of stay for triage level 2 (emergent, p<0.01), five hours longer for triage level 3 (urgent, p<0.01), and nearly two hours longer for triage level 4 (less urgent, p<0.05) cases. Conclusion: PwO were rated as less urgent and experienced longer wait times and length of stay, compared to controls matched by sex, age, and main diagnosis. Additional research is needed to confirm the consistency of these findings in other provinces/territories, and to examine clinical outcomes, and the underlying reasons for differences. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does once-weekly subcutaneous tirzepatide with diet and physical activity affect maintenance of body weight reduction in individuals with obesity or overweight? Findings: After 36 weeks of open-label maximum tolerated dose of tirzepatide (10 or 15 mg), adults (n = 670) with obesity or overweight (without diabetes) experienced a mean weight reduction of 20.9%. From randomization (at week 36), those switched to placebo experienced a 14% weight regain and those continuing tirzepatide experienced an additional 5.5% weight reduction during the 52-week double-blind period. Meaning: In participants with obesity/overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. 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 This randomized clinical trial examines the effect of tirzepatide on the maintenance of weight reduction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 glucagonlike 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 - 1 2 . 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 - 1 4 . 7% with orforglipron and was - 2 . 3% with placebo. A weight reduction of at least 1 0% by week 36 occurred in 46 to 7 5% 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. C O N C L U S I O N S 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]