GLP-1 is a hormone your gut releases after you eat. Its receptors are not only in the pancreas and the brain: they are found in the heart, the kidneys, blood vessels and immune cells. That is why the medicines that mimic it have been tested for far more than weight, and why several of those trials changed how doctors think about them.
The heart
In the SELECT trial, 17,604 adults with overweight or obesity and existing cardiovascular disease, but no diabetes, took weekly semaglutide 2.4 mg or placebo for a mean of about 40 months. The semaglutide group had 20% fewer major adverse cardiovascular events (heart attack, stroke or cardiovascular death): 6.5% versus 8.0%. The benefit appeared before most of the weight loss did, which suggests the effect is not explained by weight alone.
The kidneys
The FLOW trial followed 3,533 adults with type 2 diabetes and chronic kidney disease for a median of 3.4 years. Weekly semaglutide 1 mg lowered the risk of kidney failure, a large loss of kidney function, or death from kidney or cardiovascular causes by 24% (hazard ratio 0.76). Cardiovascular death alone fell by 29%.
The liver
In ESSENCE, adults with metabolic dysfunction-associated steatohepatitis (MASH, the inflamed form of fatty liver disease) and moderate to advanced fibrosis took weekly semaglutide 2.4 mg or placebo. At 72 weeks, 62.9% on semaglutide had resolution of steatohepatitis with no worsening of fibrosis, versus 34.1% on placebo; 37% versus 22.5% improved their fibrosis.
Sleep
The two SURMOUNT-OSA trials enrolled adults with obesity and moderate to severe obstructive sleep apnea. At one year, weekly tirzepatide reduced breathing interruptions by about 25 events per hour of sleep in people not using CPAP and by about 29 in people using it, versus about 5 on placebo in both trials. Between 43% and 52% met criteria for disease resolution.
Joints
STEP 9 enrolled 407 adults with obesity and knee osteoarthritis. Over 68 weeks, pain scores fell 41.7 points with semaglutide 2.4 mg versus 27.5 with placebo (on a 100-point scale), and physical function improved more. Semaglutide is not approved to treat osteoarthritis; the trial measures what happens to pain when weight comes down.
Inflammation
Across these trials, markers of inflammation such as C-reactive protein fall with treatment. Part of that comes from losing fat tissue, which itself produces inflammatory signals; part appears to come from GLP-1 receptors on immune cells. The size of the direct effect in people is still being worked out.
What this does not say
- Every number above comes from brand-name medicines at the doses studied, with diet and activity, in people who met each trial's criteria. Compounded semaglutide and tirzepatide were not studied in these trials.
- Sleep apnea and heart risk reduction are approved uses of specific brand-name products; osteoarthritis and liver disease are areas of research, not labels.
- Trial averages are not predictions for one person. Side effects, mostly digestive, led 16.6% of SELECT participants to stop versus 8.2% on placebo.
How we use this
Our physicians prescribe GLP-1 medicines for weight loss and follow you for years, not weeks. When you have risk factors the trials above speak to, that is part of the conversation about whether treatment fits you, and about what we measure along the way.
We do not promise outcomes from these trials. We use them to explain why weight loss done with medical follow-up is about more than a number.
Explore weight loss treatmentsSources
- 1.Lincoff AM et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med 2023. NEJM
- 2.Perkovic V et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW). N Engl J Med 2024. NEJM
- 3.Sanyal AJ et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis (ESSENCE). N Engl J Med 2025. NEJM
- 4.Malhotra A et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). N Engl J Med 2024. NEJM
- 5.Bliddal H et al. Once-weekly semaglutide in persons with obesity and knee osteoarthritis (STEP 9). N Engl J Med 2024. NEJM
- 6.Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab 2018. Cell Metabolism