5 published articles in Rct Evidence
The 2025 SURMOUNT-5 RCT established that tirzepatide produced approximately 20% mean body-weight reduction versus approximately 14% with semaglutide 2.4 mg over 72 weeks. Comparative cardiometabolic data show superior glycaemic control and lipid remodelling with dual agonism. Cardiovascular event data remain largely observational and directionally mixed in 2026.
As of 2026, two approved passive immunotherapies — lecanemab and donanemab — demonstrate statistically significant but modest slowing of cognitive decline in early Alzheimer's disease: 27% and 35% respectively on primary clinical scales versus placebo. Effect sizes are real but incremental, confined to amyloid-confirmed early-stage disease, and accompanied by clinically significant ARIA rates that constrain patient selection.
Two 2025–2026 studies — a 32-week RCT in adults with HIV-associated lipohypertrophy and a 24-week pilot in MASLD patients — both detected semaglutide's anti-aging signal primarily through DunedinPACE, a pace-of-aging clock built from longitudinal physiological data. Its structural design makes it uniquely sensitive to short-duration interventions, explaining a ~9% deceleration where cross-sectional age-estimate clocks showed weaker effects.
In the SELECT trial — a double-blind RCT of 17,604 non-diabetic adults with obesity or overweight and established cardiovascular disease — semaglutide 2·4 mg once weekly reduced the 3-point MACE composite (cardiovascular death, nonfatal MI, nonfatal stroke) by 20% over a mean 40-month follow-up (HR 0·80; 95% CI 0·72–0·90; p<0·001).
A 2025–2026 randomized, double-blind, placebo-controlled trial (NCT04019197, n=84) published in Nature Communications provides the first RCT evidence that once-weekly semaglutide measurably slows biological aging in humans. Across multiple DNA methylation clocks—including DunedinPACE, GrimAge, and PhenoAge—semaglutide-treated participants showed approximately 9% deceleration in the pace of aging versus placebo, with the strongest signals in inflammation-, brain-, and heart-linked organ-system clocks.