Drug-class and individual-agent evidence: GLP-1 receptor agonists, SGLT2 inhibitors, and the major trials behind semaglutide, tirzepatide, and related therapies.
STEP 10 phase 3 RCT: once-weekly semaglutide 2.4 mg cut bodyweight by 13.9% and drove reversion to normoglycaemia in adults with obesity and prediabetes. PICO summary and expert commentary.
Pooled subgroup analysis of STEP-HFpEF and STEP-HFpEF-DM finds once-weekly semaglutide 2.4 mg improves symptoms and weight across diuretic strata and cuts loop diuretic dose in obesity-related HFpEF. PICO summary and expert commentary.
A post-hoc pooled analysis of four randomised trials found once-weekly semaglutide lowered the composite of cardiovascular death or worsening heart failure events in patients with HFpEF, with no significant effect on cardiovascular death alone. PICO summary and expert commentary.
A prespecified FLOW analysis found once-weekly semaglutide 1 mg lowered the risk of heart failure events or cardiovascular death in adults with type 2 diabetes and chronic kidney disease. PICO summary and expert commentary.
Secondary analysis of the SELECT trial finds semaglutide 2.4 mg lowered all-cause death in adults with obesity and cardiovascular disease but no diabetes, with much of the non-cardiovascular benefit driven by fewer infectious and COVID-19-related deaths. PICO summary and expert commentary.
A prespecified pooled secondary analysis of the STEP-HFpEF trials found semaglutide improved symptoms, weight, and exercise capacity consistently across baseline C-reactive protein strata and lowered CRP regardless of weight loss. PICO summary and expert commentary.
A secondary analysis of the pooled STEP-HFpEF trials found semaglutide improved heart-failure symptoms more in obesity-related HFpEF patients with a history of atrial fibrillation than in those without. PICO summary and expert commentary.
An echocardiography substudy of the STEP-HFpEF Program found once-weekly semaglutide 2.4 mg attenuated left atrial and right ventricular remodeling versus placebo over 52 weeks. PICO summary and expert commentary.
A phase 2b randomized trial of the GLP-1/glucagon dual agonist cotadutide in type 2 diabetes and CKD, with dose-dependent reductions in albuminuria at week 14. PICO summary and expert commentary.
A post hoc analysis of the SUSTAIN 6 trial reports that once-weekly semaglutide was associated with lower odds of developing diabetic kidney disease in adults with type 2 diabetes who had no kidney disease at baseline. PICO summary and expert commentary.
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