From PAD to Substance Use: A Guide to Semaglutide’s Current and Future Uses

Type 2 diabetes

Semaglutide was first approved as Ozempic in 2017 to manage Type 2 diabetes in adults. Rybelsus (semaglutide), the first oral GLP-1 medication, was approved in 2019.

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 ages 12 and older.

In late 2025, the FDA approved a pill version of Wegovy for adults. In 2026, a higher dose (7.2 mg) of Wegovy injections was approved as Wegovy HD.

Reducing cardiovascular risk

Semaglutide has also been approved to reduce the risk of major adverse cardiovascular events (MACE) as follows:

• Ozempic injections: For people with Type 2 diabetes and heart disease

• Ozempic pills: For adults with Type 2 diabetes at high risk for cardiovascular events

• Wegovy injections and pills: For adults with cardiovascular disease and obesity or overweight

Renal protection

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

MASH

In August 2025, the FDA approved Wegovy injections to treat metabolic dysfunction-associated steatohepatitis (MASH) with liver scarring. Neither the Wegovy pills nor Ozempic (injection and pills) have this indication.

Heart failure with preserved ejection fraction (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

• Reduced need for diuretics

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

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

Semaglutide’s manufacturer resubmitted an application for HFpEF approval in 2025.

Peripheral artery disease (PAD)

The STRIDE phase 3 trial investigated semaglutide’s effect in people with Type 2 diabetes and  peripheral artery disease (PAD) with intermittent claudication (Fontaine stage IIa). At 52 weeks, participants receiving semaglutide showed significant improvements in maximum walking distance (primary outcome), pain-free walking distance, and quality of life compared to those in the placebo group. Subgroup analyses showed improvements associated with semaglutide regardless of body mass index (BMI) or diabetes duration.

Based on these data, the manufacturer has applied for a label extension, with an FDA decision expected in 2026.

Substance use disorders

A common observation among people taking semaglutide and similar medications is a decreased interest in drinking alcohol or smoking. This surprising effect has sparked research into its potential for treating substance use disorders (SUDs), including alcohol use disorder.

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, which focused on treatment-seeking adults with AUD and obesity, found that semaglutide reduced alcohol consumption.

• Nicotine dependence: The Effects of Semaglutide on Nicotine Intake and Smoking Lapse trial studied whether 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): Two studies are evaluating semaglutide’s potential in aiding recovering from OUD with and without standard medications for opioid use disorder (buprenorphine or methadone). Outcomes include opioid abstinence and reduced cravings.

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

Polyendocrine metabolic ovary syndrome (PMOS)

Another indication under investigation is polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovarian syndrome (PCOS). Studies suggest GLP-1s including semaglutide are beneficial for managing effects of PMOS, including menstrual irregularity, insulin sensitivity, body weight, and pregnancy rates. A small study found that semaglutide in combination with metformin was superior to metformin alone in body size measures and metabolic characteristics of the condition.

The RESTORE phase 3 trial will evaluate change in ovulation frequency in people ages 12 to 35 with PMOS taking semaglutide. Secondary outcomes include changes in insulin sensitivity and ovarian morphology.

Asthma

Data suggest that people with asthma and Type 2 diabetes or obesity may have better asthma control with GLP-1s.

The GATA-3 phase 2 trial is investigating semaglutide’s potential in treating asthma. The study focuses on adults with BMI over 30, without Type 2 diabetes, and with symptomatic asthma despite daily inhaled steroids. Researchers will evaluate semaglutide’s effects on asthma control and serum periostin.

Dermatologic conditions 

In clinical studies for semaglutide’s indications mentioned above, unintentional outcomes have included improvement in chronic skin conditions. While research is ongoing, the ability of GLP-1s to address both systemic inflammation and metabolic health could make them a valuable tool in treating certain dermatologic conditions.

In particular, plaque psoriasis is under investigation currently. Other conditions, such as hidradenitis suppurativa (HS) and acne vulgaris may be evaluated in the future.

Alzheimer’s dementia

Pooled data from cardiovascular outcomes trials with semaglutide or liraglutide in people with Type 2 diabetes suggested that people taking these medications may have a lower risk of dementia.

The EVOKE and EVOKE+ phase 3 trials evaluated whether oral semaglutide could slow cognitive decline and improve function in early Alzheimer’s disease. Initial results found that it did not slow progression of the condition. As a result, semaglutide's manufacturer won't be moving forward with the planned 1-year extension of the trial.

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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.

Edited by:

Mandy Armitage, MD

Mandy Armitage, MD, has combined clinical medicine with her passion for education and content development for many years. She served as medical director for the health technology companies HealthLoop (now Get Well) and Doximity.

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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