Latest GLP-1 research

SELECT — semaglutide and cardiovascular outcomes (Lincoff et al., NEJM 2023)

Randomized 17,604 adults with established cardiovascular disease, overweight/obesity, and no diabetes to semaglutide 2.4 mg weekly vs placebo. Primary endpoint: composite of cardiovascular death, nonfatal MI, or nonfatal stroke. Result: HR 0.80 (20% relative reduction) for MACE at ~3.3 years median follow-up. This was the first large trial to demonstrate cardiovascular benefit of a GLP-1 in a primary obesity indication, independent of diabetes.

FLOW — semaglutide in chronic kidney disease (Perkovic et al., NEJM 2024)

Randomized participants with type 2 diabetes and chronic kidney disease to semaglutide 1.0 mg vs placebo; stopped early for efficacy. Reported ~24% relative reduction in the composite primary endpoint of major kidney and cardiovascular outcomes. Established semaglutide as having specific renal benefits beyond glycemic control.

STEP-HFpEF — semaglutide and heart failure with preserved ejection fraction (Kosiborod et al., NEJM 2023)

In obesity-related HFpEF, semaglutide 2.4 mg improved symptom scores and 6-minute walk distance over placebo, with concurrent weight loss. Important for the framing that some benefit may be related to weight loss itself, some to direct semaglutide effects.

SURMOUNT program — tirzepatide

SURMOUNT-1 through SURMOUNT-4 have established tirzepatide's weight-loss magnitude (up to ~22% at 15 mg), its efficacy in T2D with obesity, its effect on obstructive sleep apnea (SURMOUNT-OSA), and its value for weight maintenance after an initial loss phase. SURMOUNT-MMO (cardiovascular outcomes) is underway.

TRIUMPH — retatrutide

TRIUMPH-1 (Phase 2) reported ~24% weight loss at 48 weeks on 12 mg. The Phase 3 TRIUMPH program includes weight-loss, T2D, MASH, obstructive sleep apnea, osteoarthritis, and cardiovascular outcomes trials. First Phase 3 readouts are in progress.

REDEFINE — cagrisema (cagrilintide + semaglutide)

Novo Nordisk's Phase 3 program for the fixed-dose combination of cagrilintide (amylin analog) and semaglutide. Early topline readouts reported somewhat below initial Phase 2 expectations on magnitude but still meaningful weight loss; full publications pending.

Themes emerging from the latest data

• Cardiorenal benefits extend beyond glycemic control for the GLP-1 class.
• Triple agonism (retatrutide) appears to push weight loss higher but adds mechanism-related tradeoffs.
• Muscle preservation remains the biggest open research question the field is racing to address.
• Weight maintenance post-treatment continues to show weight regain on discontinuation — implying chronic use for chronic disease, mirroring other chronic-disease drug classes.