GLP-1 medications were approved for diabetes and obesity. But a rapidly expanding body of research — backed in some cases by large clinical trials and, in at least one, an FDA approval — suggests the drug class may have meaningful effects on conditions with no obvious metabolic connection.
Here is a snapshot of where the evidence is strong, where it’s promising, and where it fell short.
1. Sleep apnea
In December 2024, the FDA approved Zepbound (tirzepatide) as the first prescription medication for adults with moderate-to-severe obstructive sleep apnea and obesity — the first time a GLP-1 receptor agonist received clearance for a condition outside diabetes and weight management. In two Eli Lilly trials spanning 52 weeks, nondiabetic patients with obstructive sleep apnea experienced a clinically meaningful reduction in breathing interruptions, and a greater proportion achieved remission or mild OSA compared to the placebo group — results seen in both PAP and non-PAP users.
Wegovy has also been forecast to reduce the prevalence of obstructive sleep apnea 10.7% by 2030 and shrink the CPAP machine market by 11% within six years.
2. Cardiovascular disease
This is the most trial-hardened area. In March 2024, Wegovy became the first injectable GLP-1 approved to reduce the risk of cardiovascular death, heart attack and stroke in obese or overweight adults with cardiovascular disease. A trial enrolling 17,604 adults across 41 countries found significant cardiovascular risk reduction within the first three months of Wegovy treatment — before clinically meaningful body weight changes occurred.
3. Kidney disease
In January 2025, Ozempic became the first GLP-1 approved to reduce the risk of worsening kidney disease in adults with Type 2 diabetes and chronic kidney disease. A Novo Nordisk trial tested Ozempic on 3,533 people with Type 2 diabetes and chronic kidney disease, and found the drug reduced the risk of kidney disease progression, and the risk of kidney and cardiovascular death by 24%.
4. Cancer
The evidence here is growing but still mixed. On the promising side: Researchers at Penn Medicine recently found women who used GLP-1 medications were about 30% less likely to develop breast cancer, with Penn now working to establish a multisite clinical trial among high-risk patients. A JAMA Oncology study of 86,632 individuals found a 17% reduction in overall cancer risk, with lower rates of endometrial, ovarian and meningioma cancers specifically. A February 2026 study found GLP-1 plus progestin therapy was associated with a 70% reduction in endometrial cancer risk compared to metformin plus progestins.
Most recently, a Cleveland Clinic study of 10,225 patients found GLP-1 use was associated with reduced disease progression across breast, prostate, colorectal, pancreatic, liver and non-small cell lung cancers. However, a Harvard review of 48 trials and more than 94,000 participants found no significant reduction in obesity-related cancer risk, with researchers noting the follow-up periods may simply be too short to detect an effect.
5. Substance use disorder
GLP-1s have also shown early promise in reducing substance use disorder risk, with researchers testing whether the drugs could treat alcohol, nicotine, cannabis and opioid use disorders. Preclinical data suggest GLP-1 receptor agonists modulate the brain’s dopamine reward pathways, reducing craving-driven behavior independent of weight loss.
6. Suicidality and mental health
The VA study found the drugs may reduce suicidal thoughts, challenging earlier concerns about their mental health effects. Separately, in January 2026, the FDA directed drugmakers to remove suicidal ideation warnings from Saxenda, Wegovy and Zepbound after reviewing 91 clinical trials and a retrospective cohort of 2.2 million patients that found no elevated psychiatric risk.
7. Osteoarthritis
A study published June 2 in Regional Anesthesia & Pain Medicine found that taking GLP-1 medications for at least three years was associated with a nearly 5-percentage-point lower chance of needing knee replacement surgery at an eight-year follow-up.
Researchers at the University of Maryland School of Medicine in Baltimore examined data from 6.8 million adults diagnosed with knee osteoarthritis between 2010 and 2024. If all eligible patients with knee arthritis and obesity or metabolic disease took semaglutide or tirzepatide for three years, the authors estimated up to 14,400 fewer knee replacements per year in the U.S. Researchers speculated the drugs may influence osteoarthritis through anti-inflammatory and analgesic mechanisms independent of weight loss — though experts noted GLP-1s are not approved for osteoarthritis and cautioned against use outside clinical trials.
A notable setback: Alzheimer’s disease
Novo Nordisk’s semaglutide failed to show a statistically significant effect in slowing Alzheimer’s progression in two late-stage phase 3 trials, both discontinued early. While semaglutide improved Alzheimer’s-related biomarkers, those improvements did not translate into clinical benefit.
What this means for health systems
The expanding indication landscape has direct operational consequences. As GLP-1s accumulate approvals and evidence across conditions, formulary committees face new questions about how broadly to support access, prior authorization teams absorb new eligibility criteria with each indication, and pharmacy leaders are increasingly being asked to weigh in on decisions that extend beyond weight management. Health systems that have treated GLP-1s as a narrow obesity drug class may need to reconsider that framing.
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