The expanding use of GLP-1s

In this article:

• Approved GLP-1 uses
• Potential expanded uses
• Keeping patients and providers up to date

In this article

• Approved GLP-1 uses
• Potential expanded uses
• Keeping patients and providers up to date

GLP-1 receptor agonists have greatly changed how we treat diabetes and obesity in recent years. Ozempic, Wegovy, and Zepbound have become popular for their ability to manage blood sugar levels and for their impressive weight-loss benefits.

GLP-1 medications are also being studied for the treatment of other conditions, which could lead to expanded FDA-approved uses. Hundreds of clinical trials are currently testing GLP-1 treatments for various conditions. With a growing demand for GLP-1 agonists, pharmacists can help guide healthcare providers and patients about proper use, potential side effects, and what to expect.

Current approved uses of GLP-1 agonists

GLP-1 receptor agonists have gained FDA approval for several medical conditions. They work by mimicking the GLP-1 hormone, which helps improve insulin secretion, suppress glucagon release, and slow gastric emptying. 

GLP-1 medications for Type 2 diabetes

Most GLP-1 agonists are approved primarily for the management of Type 2 diabetes. These GLP-1 agonists include: 

• Trulicity (dulaglutide)
• Byetta (exenatide)
• Bydureon (exenatide extended-release)
• Victoza (liraglutide)
• Adlyxin (lixisenatide)
• Ozempic (semaglutide)
• Rybelsus (semaglutide)

The drugs work best for managing glucose levels when combined with diet and exercise. Most patients see a significant drop in their A1C levels within three to six months of starting treatment, with many staying adherent after an early response. 

Mounjaro (tirzepatide) is a similar option for Type 2 diabetes that is classified as a dual GIP/GLP-1 receptor agonist. It mimics two gut hormones and has been shown to be more effective than semaglutide in managing blood sugar control. Still, many healthcare providers might not prescribe tirzepatide as a first-line treatment for Type 2 diabetes due to costs and available alternatives. 

RELATED: Are there generic GLP-1 drugs?

GLP-1 medications for weight loss

Wegovy (semaglutide) is approved for chronic weight management, as it helps patients feel full longer and manage appetite. Zepbound (tirzepatide) is another similar option to support weight loss in patients with obesity. Clinical trials have shown that patients can lose 15% of their body weight on semaglutide and up to 20% on tirzepatide. To qualify for these medications, per the FDA, patients must have:

• BMI ≥ 30, or
• BMI ≥ 27 with at least one weight-related condition, such as high cholesterol, high blood pressure, or Type 2 diabetes

Wegovy has also been approved as an oral tablet for patients who prefer not to use an injection. Foundayo (orforglipron) is another oral tablet approved by the FDA for weight loss. Unlike oral semaglutide, it can be taken at any time of day, with or without food. 

GLP-1 medications for cardiovascular risks

Some GLP-1 agonists are approved to lower the risk of heart attacks, strokes, and cardiovascular death, with the list of GLP-1s for this use continuing to grow. Victoza was the first GLP-1 approved to lower cardiovascular risks in adults with Type 2 diabetes and heart disease. Trulicity, Wegovy, and Ozempic have gained similar approvals, with Wegovy standing out for its use in adults with cardiovascular disease who have obesity. 

GLP-1 medications for sleep apnea

Zepbound is the first medication approved for obstructive sleep apnea (OSA). More specifically, it is approved for moderate to severe OSA in adults with obesity, with the SURMOUNT-OSA trial showing that tirzepatide directly lowered the apnea-hypopnea index. Other GLP-1 agonists are also being studied for OSA and could see FDA approvals for this use in the future. 

GLP-1 medications for chronic kidney disease

Ozempic is approved for reducing the risk of worsening kidney disease and cardiovascular death in adults with chronic kidney disease and Type 2 diabetes. The FLOW trial found that the risk of major kidney disease events and kidney-related death was 24% lower with semaglutide 1 mg than with placebo. Other GLP-1 medications could follow suit for approvals, with a meta-analysis showing that GLP-1 agonists significantly reduced the risk of serious kidney complications in people with Type 2 diabetes.

GLP-1 medications for liver disease

The Wegovy injection is approved for adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis. It’s the first GLP-1 medication approved for this form of liver disease. In the Phase 3 ESSENCE trial, MASH resolved without any worsening fibrosis in around 63% of patients on semaglutide versus 34% on placebo. Tirzepatide has shown similar results in other trials, although it’s not currently approved for this purpose. 

Some studies are also exploring other dual and triple hormonal agonists to improve patient outcomes. With further research, these advanced treatments could be more effective options for people living with both metabolic issues and liver problems.

Potential expanded uses of GLP-1 agonists

New research suggests that GLP-1 agonists can help treat conditions beyond their approved uses. Researchers are finding that these medications could help with heart failure, alcohol use disorder, and other conditions. 

Heart failure

The metabolic effects of GLP-1 medications may support improved cardiovascular outcomes through both direct and indirect effects. Recent studies show that GLP-1 agonists benefit patients who have heart failure with preserved ejection fraction (HFpEF). The STEP-HFpEF trial, in particular, found that semaglutide improved heart failure symptoms, walking distance, and overall quality of life in patients with HFpEF and obesity. In addition, patients on tirzepatide in the SUMMIT trial experienced improved symptoms and a reduced risk of cardiovascular death or worsening heart failure. Still, further research can help confirm these results, as GLP-1s are not approved for this use yet.

Peripheral artery disease (PAD)

Patients who struggle with PAD can look forward to potentially expanded uses of GLP1s for improving symptoms. With known benefits on metabolic health and possible direct effects  on vascular function, GLP-1 agonists could help manage walking limitations in patients with PAD. The Phase 3 STRIDE trial enrolled almost 800 adults with Type 2 diabetes and PAD and found that semaglutide 1 mg once weekly improved maximum walking distance by almost 13% 

Over placebo at 52 weeks. PAD could be a potentially new approved indication for GLP-1 medications, especially in patients with diabetes.

Alcohol use disorder

One of the more interesting potential uses of GLP-1s is addiction. Many patients on GLP-1s may report feeling less inclined to drink alcohol, which could be due to direct GLP-1 pathways in the brain. GLP-1 agonists are believed to work in the brain’s reward system to diminish cravings. 

A Phase 2 randomized controlled trial showed that low-dose semaglutide helped reduce both alcohol cravings and the amount of alcohol participants drank. In a 2026 trial, adults with alcohol use disorder and obesity taking semaglutide clocked in fewer heavy drinking days than those on placebo. Trials are still investigating this potential use case, with a current Phase 3 trial ongoing in U.S. veterans. 

Polycystic ovary syndrome (PCOS)

Studies have shown that GLP-1 agonists may also help manage metabolic problems in PCOS. One systematic review and meta-analysis found that, when used alongside standard treatments, these medications can significantly reduce body weight, BMI, and waist circumference. They also improve insulin sensitivity in women with PCOS, as shown by lower insulin resistance index (HOMA-IR) scores and fasting blood glucose.

Different pharmacological options may be used together to target various aspects of the condition, including hyperandrogenism and dyslipidemia. For example, orlistat has been found to lower testosterone levels and raise HDL in PCOS when used alongside GLP-1 drugs. As research continues, incorporating GLP-1 receptor agonists could be a treatment strategy for women with PCOS.

RELATED: Wegovy for PCOS

Migraine

GLP-1 receptor agonists are being looked at for migraine, particularly in patients with obesity. However, the evidence is preliminary so far, with a small pilot study finding that liraglutide reduced the number of monthly headache days. It didn’t measure the severity of migraine days. 

Some of the strongest evidence for headache-related benefits of GLP-1 drugs lies in studies with patients who have idiopathic intracranial hypertension. Effects on pain signaling and inflammation are currently based on animal models. As research develops, GLP-1 receptor agonists could be a complementary option for people with migraine and coexisting obesity or metabolic dysfunction.

Neurodegenerative conditions

GLP-1 agonists have shown promise as neuroprotective agents by improving memory and neuronal survival. However, the evidence is primarily based on animal studies. Recent studies in humans have shown disappointing results, with semaglutide failing to slow the progression of Alzheimer’s disease. Still, GLP-1 medications are not being ruled out for potential benefits on cognition. 

Keeping patients and healthcare providers up to date

With digital health platforms making GLP-1 therapies more accessible, pharmacists are even more crucial for looking out for patients’ health. They have the expertise to explain key details, like proper injection techniques, side effects, and new indications, to patients and healthcare providers.

What started with diabetes and weight loss is now extending to several potential uses, and the FDA is welcoming these new applications for approval. Pharmacists are now even more important in helping patients make sense of GLP-1s, especially since these medications don’t come without potential side effects. 

Expert takeaway

“GLP-1 drugs are no longer just diabetes and weight-loss drugs, and the approved uses are growing fast. But the Alzheimer’s research is a good reminder that we shouldn’t let our hopes and biases get in the way of the evidence, since early findings don’t always hold up in larger clinical trials,” says Gerardo Sison, Pharm.D., a member of the SingleCare Medical Review Board.