Daily Endocrinology Research Analysis

A suboptimal clinical response after metabolic and bariatric surgery (MBS) is common and carries considerable health concerns. Here a double-blinded, randomized (1:1), placebo-controlled trial using semaglutide 2.4 mg weekly (BARI-STEP) recruited adult participants at least 1 year after gastric bypass or sleeve gastrectomy with a suboptimal clinical response, defined as less than 20% weight loss from surgery. This was an adjunct to lifestyle intervention with a 500-kcal daily energy deficit. The primary outcome was percentage weight loss after 68-week treatment on an intention-to-treat analysis. Seventy participants (mean (s.d.) age = 47.3 (10.3) years, 58 (82.9%) female and 12 (17.1%) male) were randomized to receive 2.4 mg semaglutide (n = 35) or placebo (n = 35). The intention-to-treat sample included 63 participants. Estimated change in mean (s.d.) percentage weight loss from baseline to week 68 was -18.0 (9.2) with semaglutide 2.4 mg (n = 34) versus +0.4 (7.0) with placebo (n = 29). The mean adjusted treatment difference in percentage body weight change for semaglutide 2.4 mg versus placebo was -19.18 (95% confidence interval -23.4 to -14.8; P < 0.001). Adverse events (AEs) were consistent with the known safety and tolerability profile of semaglutide, with no new safety concerns for the post-bariatric population. There were eight serious AEs, one suspected unexpected serious adverse reaction and no treatment-related deaths. BARI-STEP demonstrates that in people with a suboptimal clinical response after MBS, semaglutide results in substantial and clinically significant body weight reduction along with improvement in metabolic parameters and quality of life, compared to placebo. These findings suggest that semaglutide 2.4 mg is a safe and effective treatment option for this patient population. ClinicalTrials.gov: NCT05073835 .

BACKGROUND: Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework. METHODS: We conducted a frequentist random-effects NMA of randomized controlled trials comparing novel ABTs with placebo or active comparators in R. Primary outcome was the percent change in body weight from baseline. Secondary outcomes included absolute weight changes, anthropometric measures, and overall and specific GI adverse events (AEs). Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores. RESULTS: Six trials (N = 4642; 12-68 weeks) were included. Compared with placebo, high dose (HiD) subcutaneous amycretin produced the largest reduction in percent body weight (mean difference -23.95%; P score 1.00), followed by HiD eloralintide (-18.01%; P score 0.89) and HiD CagriSema (-17.18%; P score 0.85), all exceeding semaglutide 2.4 mg (-11.45%) and liraglutide 3.0 mg (-6.4%). Almost similar patterns were observed for absolute weight, body mass index, waist circumference and categorical weight-loss thresholds. GI AEs, nausea, vomiting and constipation were more common with HiD ABTs, especially oral amycretin and CagriSema, while diarrhoea mainly increased with semaglutide 2.4 mg. Only HiD CagriSema increased AE-related discontinuation. CONCLUSIONS: Novel ABTs, such as HiD amycretin, CagriSema and eloralintide, may induce substantial short- to medium-term weight loss but may also increase GI AEs; given sparse, low-certainty data, these findings are preliminary and require confirmation in larger trials. TRIAL REGISTRATION: The meta-analysis was registered in PROSPERO (CRD420261340457). The review protocol summary can be accessed at the PROSPERO website (https://www.crd.york.ac.uk/PROSPERO/view/CRD420261340457).

BACKGROUND: Type 2 diabetes poses a growing public health burden in low- and middle-income countries, where major gaps in access to chronic care persist. Task-shifting to Community Health Workers (CHWs) and the use of digital clinical decision support systems may bridge these gaps. Randomized trials evaluating CHW-led care models in which CHWs initiate, titrate, and monitor first-line diabetes treatment are lacking. METHODS: We conducted a cluster-randomised trial nested within the ComBaCaL (Community-Based Chronic Care Lesotho) cohort (NCT05596773). The cohort spans 103 rural villages in Lesotho, managed by trained, supervised CHWs. After home-based screening of cohort participants ≥40 years old or with body mass index ≥25 kg/m RESULTS: From 13 May 2023 to 31 January 2024, 5'785 cohort participants were screened, 252 (4·4%) diagnosed with type 2 diabetes, and 103 (51 control, 52 intervention) included in the primary analysis (73·8% female, mean age 62·3 ± 12·8 years, mean HbA1c 7·2 ± 1·4%). At 12 months, HbA1c was 7·1 ± 1·9% in the control arm and 6·5 ± 1·3% in the intervention arm (adjusted mean difference -0·46%, 95%CI -1·14 to 0·22). Engagement in care was higher in the intervention arm. No relevant difference in safety outcomes was observed. CONCLUSIONS: CHW-led, clinical decision support system-assisted management of type 2 diabetes, including first-line drug prescription, may improve engagement in care and glycaemic control in rural low-resource settings. Larger studies are required to confirm these findings. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05743387.