Author: Hormone Insight Editorial Team

A phase 1 crossover study of the IcoSema fixed-ratio combination of insulin icodec and semaglutide reports unchanged icodec exposure but a higher, earlier semaglutide peak versus separate injections. PICO summary and expert commentary.

A model-based analysis of a 28-week randomized meal-test substudy comparing tirzepatide 15 mg with semaglutide 1 mg in metformin-treated type 2 diabetes. PICO summary and expert commentary.

Post hoc analysis of the STEP 1, 2, 3, and 5 trials finds semaglutide 2.4 mg did not increase depression or suicidal ideation versus placebo in people without major psychopathology. PICO summary and expert commentary.

Prespecified FLOW subgroup analysis testing whether semaglutide’s kidney and cardiovascular benefits hold with or without baseline SGLT2 inhibitor use. PICO summary and expert commentary.

An exploratory imaging substudy of a 32-week randomised trial finds semaglutide and empagliflozin each lower cortical apparent diffusion coefficient and reduce total kidney volume in type 2 diabetes. PICO summary and expert commentary.

PIONEER 11 found that oral semaglutide monotherapy lowered HbA1c at all doses versus placebo in drug-naive, predominantly Chinese adults with type 2 diabetes, with weight reduction confined to the 7 mg and 14 mg doses. PICO summary and expert commentary.

Clinical Context Prediabetes affects approximately 96 million American adults—more than one-third of the adult population—and represents a critical window for diabetes prevention. Without intervention, 5-10% of individuals with prediabetes progress to type 2 diabetes annually, with up to 70% eventually developing the disease. Beyond diabetes risk, prediabetes itself is associated with increased cardiovascular disease, nephropathy, and neuropathy, making early intervention imperative. Landmark trials like the Diabetes Prevention Program (DPP) demonstrated that intensive lifestyle intervention can reduce diabetes incidence by 58%, while metformin provides a more modest 31% reduction. However, sustaining lifestyle changes long-term remains challenging, and metformin’s effects are primarily…

Summary: In adults with obesity-related HFpEF (BMI ≥30) from pooled STEP-HFpEF trials (n=1,145), stratified by baseline diuretic use, once-weekly semaglutide 2.4 mg for 52 weeks produced consistent weight reduction (-6.9% to -8.8%), greater symptom improvement in loop diuretic users (+9.3 vs +4.7 KCCQ points), and reduced loop diuretic doses by 17% compared to placebo (which showed 2.4% diuretic dose increase), with no significant safety signals across diuretic subgroups. PICO Description Population Adults with obesity-related HFpEF (BMI ≥30), pooled STEP-HFpEF trials (n=1,145), stratified by diuretic use. Intervention Semaglutide 2.4 mg subcutaneously once weekly for 52 weeks plus standard HFpEF care. Comparison…

A post-hoc pooled analysis of four semaglutide trials reports fewer worsening heart failure events in participants with HFpEF, with no significant effect on cardiovascular death. PICO summary and expert commentary.

A prespecified analysis of the FLOW randomised trial found once-weekly semaglutide reduced heart failure events and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. PICO summary and expert commentary.