New FDA Indications for GLP-1s: Heart Failure, PAD, MASH & Beyond

When semaglutide and tirzepatide first hit the market, they had two indications: type 2 diabetes and chronic weight management. In 2026, that list is rapidly expanding. New FDA approvals and pending applications are positioning GLP-1 medications as treatments for an increasingly wide range of conditions—with major implications for insurance coverage and patient access.

Already Approved: Current FDA Indications

Obstructive Sleep Apnea: A Game-Changer

Zepbound (tirzepatide) became the first-ever medication approved specifically for obstructive sleep apnea (OSA) in December 2024, based on the SURMOUNT-OSA trial. The results were remarkable: patients experienced an average reduction of 23.8 events per hour in their apnea-hypopnea index (AHI), with many patients moving from severe sleep apnea to mild or even resolution.

This is significant because OSA affects an estimated 30 million Americans, and the current standard treatment—CPAP machines—has notoriously poor adherence. Studies show that 40-60% of patients stop using CPAP within the first year. A medication-based alternative that also addresses the underlying obesity driving most OSA cases represents a fundamentally different approach.

For patients, the sleep apnea indication opens an important insurance pathway. If your insurer doesn’t cover GLP-1s for obesity alone, an OSA diagnosis may provide an approved clinical rationale for coverage.

MASH (Fatty Liver Disease): 63% Resolution

In August 2025, Wegovy became the first GLP-1 approved for MASH (metabolic dysfunction-associated steatohepatitis), formerly known as NASH. The ESSENCE trial showed that 62.9% of patients achieved steatohepatitis resolution compared to 34.3% on placebo, and 36.8% achieved fibrosis improvement.

MASH affects approximately 15 million Americans and is a leading cause of liver transplants. Before this approval, no medication had been approved specifically for MASH treatment—the only proven intervention was weight loss through lifestyle changes or bariatric surgery.

Heart Failure: STEP-HFpEF Results

While semaglutide doesn’t yet have a standalone FDA indication for heart failure, the STEP-HFpEF trial (presented in 2023) showed that semaglutide significantly improved heart failure-related symptoms, physical limitations, and exercise capacity in patients with obesity-related heart failure with preserved ejection fraction (HFpEF).

HFpEF is a growing epidemic, increasingly driven by obesity, and has historically had few effective treatments. The SELECT trial’s prespecified heart failure analysis (published in The Lancet in 2024) showed semaglutide reduced MACE, heart failure hospitalizations, and cardiovascular death in patients with both HFpEF and HFrEF (heart failure with reduced ejection fraction).

Cardiologists increasingly prescribe GLP-1 medications off-label for heart failure patients with obesity, and a specific heart failure indication could follow as more dedicated trial data matures.

Peripheral Artery Disease: STRIDE Trial

The STRIDE trial, presented at ACC 2025, tested semaglutide in patients with peripheral artery disease (PAD) and type 2 diabetes. Results showed a statistically significant 13% improvement in maximum walking distance and meaningful improvement in pain-free walking distance.

PAD affects approximately 6.5 million Americans over age 40, and treatment options beyond exercise rehabilitation and surgical revascularization are limited. The STRIDE results suggest GLP-1s may improve quality of life for PAD patients by addressing the inflammatory and metabolic drivers of peripheral vascular disease.

Tirzepatide Cardiovascular Outcomes: SURPASS-CVOT

While semaglutide’s cardiovascular benefits are established (via SELECT), tirzepatide’s cardiovascular outcomes trial (SURPASS-CVOT) confirmed that tirzepatide also provides robust cardiovascular protection in patients with type 2 diabetes. This positions Mounjaro/Zepbound as a cardioprotective medication alongside its weight-loss and diabetes benefits.

Eli Lilly’s SURMOUNT-MMO trial is currently enrolling patients to test whether tirzepatide reduces cardiovascular events in patients with obesity but without diabetes—similar to what SELECT demonstrated for semaglutide. Results are expected around 2027-2028 and could secure a cardiovascular indication for Zepbound specifically.

Pending and Upcoming Trials

Why New Indications Matter for You

Every new FDA indication opens a potential insurance coverage pathway. If your insurer denies coverage for obesity alone, an approved indication for sleep apnea, heart failure, or MASH could provide the clinical justification needed for approval. Many patients are working with their physicians to document qualifying conditions that match approved indications.

The rapid expansion of GLP-1 indications reflects a growing understanding that these medications address fundamental metabolic and inflammatory processes that drive multiple chronic diseases. As the evidence base continues to grow, expect the list of approved uses to expand further.

Sources

1. FDA approval notices: Wegovy CV indication (March 2024), Zepbound OSA (December 2024), Wegovy MASH (August 2025), Wegovy pill (December 2025).
2. SURMOUNT-OSA trial. Eli Lilly press release. 2024.
3. ESSENCE trial. MASH resolution data. 2025.
4. STRIDE trial. ACC 2025 presentation.
5. SURPASS-CVOT. Published results. 2025.
6. ClinicalTrials.gov. SURMOUNT-MMO, TRIUMPH-OUTCOMES, TREASURE-CKD, FOCUS registrations.