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.
Author: Hormone Insight Editorial Team
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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.
In adults with diabetes mellitus but no evident cardiovascular disease, aspirin at a dose of 100 mg daily significantly reduced the risk of serious vascular events by 12% compared to placebo, though it was associated with a 29% increased risk of major bleeding events.
Summary: In healthy Chinese adults (n=32), once-daily oral semaglutide escalated from 3 mg to 14 mg over 12 weeks demonstrated dose-dependent exposure (AUC, Cmax) comparable to global populations, with significant reductions in body weight (P=0.0001) and fasting glucose (P=0.0011) compared to matching placebo, with primarily GI adverse events (nausea, decreased appetite), no severe hypoglycemia or serious AEs. PICO Description Population Healthy Chinese adults (n=32), randomized to oral semaglutide or placebo. Intervention Once-daily oral semaglutide with dose escalation 3 mg → 7 mg → 14 mg over 12 weeks. Comparison Matching placebo under identical conditions (fasting, 30-min post-dose fasting). Outcome Dose-dependent…
Clinical Context Obesity affects over 650 million adults worldwide and is associated with numerous comorbidities including type 2 diabetes, cardiovascular disease, obstructive sleep apnea, and certain cancers. Beyond physical health, obesity significantly impacts quality of life, physical functioning, and psychological wellbeing. Traditional weight management approaches combining diet and exercise typically achieve modest weight loss of 3-5%, often insufficient to meaningfully improve health outcomes or quality of life. The STEP (Semaglutide Treatment Effect in People with obesity) program represents the largest clinical trial program for anti-obesity pharmacotherapy to date. These Phase 3 trials evaluated semaglutide 2.4 mg—a GLP-1 receptor agonist administered…
Clinical Context The relationship between obesity and cardiovascular disease has long been recognized, but proving that weight loss reduces cardiovascular events has proven challenging. Previous weight loss interventions—whether through lifestyle modification, bariatric surgery, or medications—have struggled to demonstrate reduced cardiovascular mortality in randomized trials. This evidentiary gap led some to question whether obesity itself causes cardiovascular events or merely travels alongside other risk factors. The SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) fundamentally changed this landscape. It was the first dedicated cardiovascular outcomes trial of an anti-obesity medication in patients without diabetes, and it…
Summary: In adults with overweight/obesity (BMI ≥27) and established atherosclerotic CVD, without diabetes, semaglutide 2.4 mg once weekly for median 3.4 years significantly reduced composite kidney endpoint (kidney failure, ≥50% eGFR decline, kidney death), slowed annual eGFR decline by 1.16 mL/min/1.73m², and reduced all-cause mortality by 20% compared to matching placebo, with fewer serious adverse events (49.6% vs 53.8%) and greater benefit in patients with baseline eGFR <60. PICO Description Population Adults with overweight/obesity (BMI ≥27) and established CVD, without diabetes, from SELECT trial. Intervention Semaglutide 2.4 mg subcutaneously once weekly for median 3.4 years. Comparison Matching placebo weekly for…