Drug-class and individual-agent evidence: GLP-1 receptor agonists, SGLT2 inhibitors, and the major trials behind semaglutide, tirzepatide, and related therapies.
Pooled patient-reported outcomes from the STEP 1-4 trials show semaglutide 2.4 mg improved physical functioning versus placebo over 68 weeks. PICO summary and expert commentary.
A prespecified analysis of the SELECT randomised trial showing sustained four-year weight loss with semaglutide versus placebo in adults with cardiovascular disease and obesity but no diabetes. PICO summary and expert commentary.
Secondary analysis of the SELECT trial finds once-weekly semaglutide 2.4 mg modestly lowered a composite kidney endpoint versus placebo in adults with overweight or obesity and cardiovascular disease but no diabetes. PICO summary and expert commentary.
Prespecified pooled analysis of the STEP-HFpEF program: once-weekly semaglutide 2.4 mg improved NYHA functional class versus placebo in obesity-related HFpEF. PICO summary and expert commentary.
In the FLOW trial, once-weekly semaglutide 1.0 mg lowered the risk of major kidney disease events and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. PICO summary and expert commentary.
A prespecified secondary analysis of the pooled STEP-HFpEF and STEP-HFpEF DM trials shows once-weekly semaglutide 2.4 mg lowered NT-proBNP and improved symptoms in obesity-related HFpEF. PICO summary and expert commentary.
In patients with type 2 diabetes (T2D), once-weekly semaglutide significantly increased the risk of developing nonarteritic anterior ischemic optic neuropathy (NAION) compared to non-exposure, doubling the five-year hazard ratio (HR), though it was associated with improved glycaemic control and other cardiometabolic benefits.
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