From Diabetes to Alzheimer’s: Live Updates on Semaglutide’s Current and Future Uses

Semaglutide (Ozempic, Rybelsus, Wegovy) has quickly become a staple for Type 2 diabetes and weight loss. Known for its effectiveness and versatility, it’s one of the most popular medications in its class. But its story doesn’t stop there.

Ongoing research is uncovering new potential uses, from heart and kidney disease to neurological and metabolic conditions. Here’s what you need to know about semaglutide’s current and future applications.

What is semaglutide?

Semaglutide belongs to the glucagon-like peptide-1 (GLP-1) receptor agonist class. It mimics a natural gut hormone called GLP-1, which helps regulate blood glucose (sugar), appetite, and digestion. It does this by attaching to GLP-1 binding sites (receptors), which are located throughout the body.

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Available as injections (Ozempic, Wegovy) and an oral pill (Rybelsus), semaglutide works by:

• Causing the pancreas to release insulin after meals

• Reducing glucose production in the liver

• Slowing the movement of food out of the stomach

• Targeting areas of the brain that regulate appetite and fullness

Researchers are still uncovering other ways semaglutide works in the body, broadening its potential applications.

Approved semaglutide uses

Semaglutide is already approved for several key uses. These include Type 2 diabetes, weight loss, and lowering the risk of serious cardiovascular and kidney-related problems in certain people.

Type 2 diabetes

Semaglutide was first approved as Ozempic in 2017 to manage Type 2 diabetes in adults. The SUSTAIN clinical trials showed its ability to significantly lower hemoglobin A1C (HbA1C or A1C). A1C is a test that measures average blood glucose levels over the last 3 months.

Key SUSTAIN findings include:

• A1C reduction ranging from 1.2% to 2.2%, depending on the semaglutide dose

• Greater A1C reduction compared to other GLP-1s, including dulaglutide (Trulicity) and extended-release exenatide (Bydureon BCise)

• Better blood glucose management as add-on treatment compared to insulin glargine (Lantus) and sitagliptin (Januvia)

• Significant reductions in body weight

EXPERT PICKS: WHAT TO READ NEXT

• Compare semaglutide injections: See what experts say about the similarities and differences between Ozempic and Wegovy, two brand-name versions of semaglutide.

• How does it work? Learn about how semaglutide works for weight loss.

• Possible side effects: Read about semaglutide’s potential side effects — from diarrhea to hair loss — and how to manage them.

Rybelsus, the first oral GLP-1 medication, was approved in 2019. It gave people using Ozempic a needle-free alternative. The PIONEER trials showed that Rybelsus was also effective at lowering A1C and promoting weight loss.

Key PIONEER findings include:

• A1C reduction up to 1.4% with the highest dose (14 mg)

• Better blood glucose management as add-on treatment compared to sitagliptin and empagliflozin (Jardiance)

• Weight-loss benefits, particularly at higher doses

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Weight loss

In 2021, semaglutide was approved as Wegovy for weight loss in adults considered obese, or overweight with related health conditions. The following year, Wegovy’s approval was expanded to include certain adolescents age 12 and older.

Results from the STEP clinical trials helped fuel semaglutide’s popularity for weight loss. Key findings showed that semaglutide use was associated with:

• An average weight loss of 15% to 17% over 68 weeks (about 16 months)

• Greater weight loss compared to liraglutide (Saxenda), another GLP-1 medication for weight loss

• Positive effects on health markers such as blood pressure, cholesterol, and blood glucose levels

Oral semaglutide isn’t currently approved for weight loss. But higher doses (25 mg) have shown comparable results to Wegovy, making approval possible in the near future.

Cardiovascular risk reduction

Semaglutide also has proven benefits for people with heart disease. During the SELECT and SUSTAIN-6 trials, semaglutide lowered the risk of major adverse cardiovascular events (heart attack, stroke, or cardiovascular death), or MACE, by 20% and 26%, respectively.

Ozempic is approved to lower the risk of MACE in people with Type 2 diabetes and heart disease. Wegovy recently gained approval for this use in people with heart disease and a larger body size. Rybelsus doesn’t have this indication, but that could change in 2025.

Chronic kidney disease

In January 2025, the FDA approved semaglutide (as Ozempic) to lower the risk of kidney disease worsening, kidney failure, and cardiovascular death in adults with Type 2 diabetes and CKD. Ozempic is the first and only GLP-1 medication approved for this use.

Semaglutide’s kidney benefits have been seen in other studies. But the FLOW trial specifically looked at its impact on major kidney disease events, which included at least one of the following:

• Kidney failure

• Kidney transplant

• Dialysis

• Loss of 50% or more of kidney function

• Death from kidney-related or cardiovascular causes

Key FLOW findings showed the following with semaglutide compared to placebo (injection without medication):

• 24% reduction in the risk of major kidney disease events

• 18% lower risk of MACE

• 20% lower risk of death from any cause

• Slower decline in kidney function

Semaglutide pipeline

Semaglutide’s impact extends beyond its current FDA-approved uses. Researchers are exploring its potential to address a variety of other health conditions. Several uses are being studied in phase 3 trials — the last step before the manufacturer applies for approval. Others are in phase 2 trials, which are earlier trials to see if semaglutide works for a specific use.

Here are some of the most promising areas under investigation.

Heart failure with preserved ejection fraction (HFpEF)

Semaglutide is being studied for HFpEF in people considered obese. With HFpEF, the heart muscle contracts normally but is too stiff to fill properly with blood. This can lead to symptoms such as shortness of breath, swelling, and decreased ability to exercise. Having a larger body can worsen symptoms and is thought to be a potential cause of HFpEF.

The STEP-HFpEF and STEP-HFpEF DM phase 3 trials looked at semaglutide’s impact on heart failure symptoms and physical limitations. A pooled analysis of four trials also looked at heart failure events. Here’s how semaglutide stacked up to placebo:

• Significantly reduced heart failure symptoms and physical limitations

• Improved exercise capacity and 6-minute walk distance

• Significant weight loss

• Reduced need for diuretics (water pills) to remove fluid buildup

• 31% lower risk of cardiovascular death or heart failure events

• 41% lower risk of worsening heart failure events (such as hospitalization)

Semaglutide’s manufacturer plans to apply for HFpEF approval in early 2025.

Metabolic dysfunction-associated steatohepatitis (MASH)

Semaglutide has shown promise in treating MASH, a health condition caused by excess fat and inflammation in the liver. MASH is a leading cause of cirrhosis. And until recently, there hadn’t been any FDA-approved treatments. Looking ahead, semaglutide could become another option for MASH as soon as late 2025 or early 2026.

ESSENCE is a two-part phase 3 trial evaluating semaglutide in adults with MASH and moderate to advanced liver fibrosis (scarring). The first part looked at changes in liver inflammation and scarring, with initial data showing that semaglutide:

• Improved liver fibrosis without worsening inflammation (steatohepatitis)

• Resolved liver inflammation in many participants

• Improved liver function tests

The second part of the trial is looking at liver-related events, such as cirrhosis. It’s set to wrap up in 2029.

Peripheral artery disease

Peripheral artery disease (PAD) is caused by narrowed blood vessels that reduce blood flow to the limbs. As a common complication in people with Type 2 diabetes, it can increase the risk of serious cardiovascular events, chronic wounds, and amputations. Researchers are now exploring the potential benefits of semaglutide for people with PAD and Type 2 diabetes.

The STRIDE phase 3 trial investigated semaglutide’s impact on walking distance, quality of life, and blood flow to the legs, among other outcomes. The study has been completed, but results aren’t available yet. The manufacturer anticipates applying for approval in the first half of 2025.

Alzheimer’s disease

Researchers are investigating oral semaglutide as a potential treatment for early Alzheimer’s disease. This was prompted by data linking semaglutide to a lower risk of dementia, among other effects. It’s thought that it may have protective and anti-inflammatory effects in the brain.

The EVOKE and EVOKE+ phase 3 trials will help determine if semaglutide can slow cognitive decline and improve function in early Alzheimer’s disease. Initial results from the trials are expected in 2025.

Polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a common hormone imbalance in women. It can cause symptoms such as irregular menstrual cycles, weight gain, and infertility. Insulin resistance — when the body doesn’t respond as well to insulin — is a key factor in PCOS.

Early studies have highlighted potential benefits of semaglutide for managing PCOS. This includes improving insulin sensitivity, normalizing menstrual cycles, and causing weight loss. These effects may also improve fertility, which may have contributed to a trend of unexpected pregnancies after starting semaglutide resulting in “Ozempic babies.”

The RESTORE phase 3 trial will help confirm if semaglutide has benefits for women with PCOS. Researchers will look at how it affects ovulation, insulin sensitivity, and other factors. The study includes girls and women ages 12 to 35 with PCOS and a larger body size.

Parkinson’s disease

Parkinson’s disease (PD) is a neurological condition that affects movement, coordination, and quality of life. Current treatments primarily address symptoms but don’t slow down progression. Similar to Alzheimer’s disease, researchers think that semaglutide’s effects in the brain could also benefit PD.

The GIPD phase 2 trial is planning to investigate potential semaglutide benefits in adults ages 40 to 75 with newly diagnosed PD. It will look at changes in motor symptoms, cognitive function, quality of life, and other factors. The trial was first registered in 2018 and was expected to be completed in 2024. But its status hasn’t been updated yet.

Substance use disorders

You may have heard about people losing interest in drinking alcohol or smoking after starting semaglutide. This surprising effect has sparked research into its potential for treating substance use disorders (SUDs), including alcohol use disorder. Animal studies suggest that GLP-1s may affect the reward system in the brain and reduce cravings.

Several phase 2 trials are looking at semaglutide’s potential role in SUDs, including:

• Alcohol use disorder (AUD): Multiple trials are investigating semaglutide’s potential to reduce alcohol consumption and cravings in adults with AUD. These include the STAR and Rybelsus in AUD trials. The SEMALCO trial is focusing on adults with AUD and a larger body size.

• Nicotine dependence: The Effects of Semaglutide on Nicotine Intake and Smoking Lapse trial is seeing if semaglutide can reduce cravings and smoking behavior in people with nicotine dependence. Preliminary findings suggest that it’s safe for this use.

• Opioid use disorder (OUD): The SHORE trial is looking at semaglutide’s potential in aiding recovering from OUD. The trial focuses on whether it can help manage cravings, improve metabolic health, and support recovery when combined with existing treatments.

• Cocaine use disorder: The STAC trial is investigating whether semaglutide can reduce cravings and use in people with cocaine use disorder, including those living with HIV.

Asthma

Having a larger body is a risk factor for developing asthma, a chronic respiratory condition. It can also worsen symptoms and make asthma harder to manage. Emerging research suggests that semaglutide may offer benefits beyond weight loss for certain people with asthma.

The GATA-3 phase 2 trial is investigating semaglutide’s potential in treating asthma. The study focuses on adults with larger body size and asthma that isn’t well-managed with inhaled steroids. Researchers will see if semaglutide can reduce airway inflammation and improve asthma management.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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