Top 10 Emerging Uses of GLP-1 Compounds Beyond Diabetes and Obesity

Heart Protection That Does Not Depend on Weight Loss

The SELECT trial enrolled more than 17,000 adults with cardiovascular disease and overweight or obesity, none of whom had diabetes, and followed them for a mean of 34 months. Semaglutide cut the combined risk of cardiovascular death, heart attack and stroke by 20 percent compared with placebo, and all cause mortality dropped by 19 percent. What surprised cardiologists was the timing: the curves separated within months, long before most participants had lost enough weight to explain a cardiovascular benefit on its own, which points to a more direct effect on inflammation and vascular function.

MACE risk reduction vs placebo · SELECT trial, NEJM

Slowing Chronic Kidney Disease

The FLOW trial followed 3,533 people with type 2 diabetes and chronic kidney disease for a median of 3.4 years - the first dedicated kidney outcomes trial ever run on a GLP-1 medication. Semaglutide reduced the risk of major kidney events by 24 percent, cardiovascular events by 18 percent, and death from any cause by 20 percent. The benefit held steady whether patients had mild, moderate or severe kidney disease, and whether or not they were already on an SGLT2 inhibitor. The FDA approved this use in January 2025.

Risk reductions across endpoints vs placebo · FLOW trial, NEJM 2024

Easing Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction, or HFpEF, is notoriously hard to treat, and roughly 60 percent of patients with it also carry obesity. In the STEP HFpEF program, semaglutide improved symptom scores on the Kansas City Cardiomyopathy Questionnaire by 16.6 points against 8.7 for placebo, increased six minute walk distance, and cut C reactive protein by 43.5 percent. Patients also needed less loop diuretic medication. This is not yet a formal FDA approved indication, but the data has already shifted how cardiologists think about obesity related heart failure.

KCCQ symptom score improvement · STEP HFpEF trials, Circulation and Nature Medicine

Reversing Early Stage Liver Scarring

Metabolic dysfunction associated steatohepatitis, or MASH, used to be a disease with almost no pharmaceutical options. In the phase 3 ESSENCE trial, 800 patients with biopsy confirmed MASH and moderate to advanced fibrosis were followed for 72 weeks. Among those on semaglutide, 62.9 percent achieved resolution of steatohepatitis without their fibrosis getting worse, compared with 34.3 percent on placebo. A third of treated patients achieved both steatohepatitis resolution and measurable fibrosis improvement at the same time. This became the first GLP-1 medication approved specifically for liver disease with fibrosis, excluding cirrhosis.

MASH resolution without worsening fibrosis at week 72 · ESSENCE trial, NEJM 2025

Treating Obstructive Sleep Apnea

Obstructive sleep apnea affects an estimated 936 million adults worldwide, and until the end of 2024 there was no approved drug for it at all. That changed when tirzepatide became the first medication ever approved specifically for moderate to severe OSA, based on the SURMOUNT OSA trials. Over 52 weeks, tirzepatide reduced the apnea hypopnea index by 25 to 29 events per hour compared with 5 events per hour on placebo, and roughly 43 to 51 percent of participants saw their sleep apnea resolve entirely.

Apnea hypopnea index over 52 weeks · SURMOUNT OSA trials, NEJM 2024

Reducing Pain From Knee Osteoarthritis

The STEP 9 trial tested semaglutide in adults with obesity and moderate to severe knee osteoarthritis pain over 68 weeks. Beyond the expected weight loss, patients on semaglutide showed a significantly larger improvement in physical function on the SF-36 survey, gaining 12.0 points compared with 6.5 points on placebo. Knee pain scores on the WOMAC scale dropped more sharply as well. Newer data on cartilage thickness and joint biomechanics is starting to suggest the benefit is not purely a byproduct of carrying less weight, though that research is still early.

Physical function improvement · STEP 9 trial, NEJM 2024

Cutting Heavy Drinking in Alcohol Use Disorder

A randomized, double blind, placebo controlled trial published in The Lancet in May 2026 followed 108 people with obesity and alcohol use disorder for 26 weeks. Those on weekly semaglutide cut their heavy drinking days by 41.1 percent from baseline, compared with a 26.4 percent reduction in the placebo group, alongside cognitive behavioral therapy in both arms. Earlier, smaller trials out of USC and the NIH found similar reductions in craving and consumption, and the NIH has called the early signal encouraging while noting that larger confirmatory trials are still needed.

Reduction in heavy drinking days from baseline · Lancet, May 2026

Protecting the Brain From Inflammation

GLP-1 receptors sit throughout the hypothalamus and brainstem, well beyond the gut, and researchers have been probing what that means for cognition. The working theory is that these compounds cross into the central nervous system and dampen neuroinflammation while improving blood flow, both of which are implicated in cognitive decline. Trials specifically studying Alzheimer's disease and other forms of dementia are still in progress, and none have reported the kind of definitive outcome data seen in the cardiovascular or kidney trials. It remains one of the most closely watched frontiers in the field precisely because the mechanism is plausible but the proof is not yet complete.

Supporting Hormonal Balance in Midlife

Beyond insulin, GLP-1 activity appears to touch other hormonal systems tied to energy regulation and metabolic stability. Clinicians working in midlife and hormone focused practices have reported improvements in markers connected to insulin resistance and lipid metabolism in patients using these compounds, changes that may indirectly support more stable hormone patterns and fewer of the energy dips and cravings associated with metabolic fluctuation. This area is still built mostly on clinical observation and smaller studies rather than large randomized trials, so it belongs firmly in the watch and wait category.

Quieting Cravings Beyond Alcohol

The same reward pathway effects behind the alcohol findings above appear to extend to other substances. In subgroup data from the USC led trial on alcohol use disorder, participants who also smoked cigarettes showed a greater drop in cigarettes per day on semaglutide than on placebo. Researchers at the National Institute on Drug Abuse have described this as a genuinely new direction for addiction pharmacology, one that may eventually extend to opioids and other substances, though that work is still confined to early trials and preclinical models.