GLP-1 Receptor Agonists: A Comprehensive Overview of Usage, Impact, and Discontinuation

Nearly one in eight U.S. adults now report using GLP-1 medications, highlighting their growing role in managing type 2 diabetes and obesity.

Medication Usage and Patient Population

GLP-1 receptor agonists, including semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), are prescribed for type 2 diabetes and weight management. A late 2025 KFF poll found approximately one in eight U.S. adults currently use these medications. In the UK, an estimated 1.6 million adults have used these injections in the past year, predominantly through private prescriptions.

Clinical and Market Competition

Novo Nordisk, manufacturer of Ozempic and Wegovy, has forecasted a 13% decline in sales for the current year, citing increasing competition and pricing pressures. Eli Lilly's Mounjaro has become Australia's highest-selling prescription medication brand. Both companies are developing next-generation drugs, including oral formulations and multi-receptor agonists.

Impact on Substance Use Disorders

Alcohol Use Disorder

A randomized controlled trial of 108 patients with obesity and alcohol use disorder found that those receiving semaglutide experienced a 41.1% reduction in heavy drinking days over 26 weeks, compared to 27.4% in the placebo group. All participants also received cognitive behavioral therapy. The number needed to treat (NNT) was 4.3.

Multiple Substance Use Disorders

An observational study published in the British Medical Journal analyzed electronic health records from 606,434 U.S. veterans with type 2 diabetes over up to three years. For participants without a prior addiction diagnosis, GLP-1 use was associated with:

• 18% lower risk for alcohol use disorder
• 14% lower risk for cannabis use disorder
• 20% lower risk for cocaine use disorder
• 20% lower risk for nicotine use disorder
• 25% lower risk for opioid use disorder

For individuals with an existing substance use disorder, GLP-1 prescription was associated with:

• 39% reduction in overdose risk
• 31% reduction in emergency department visits
• 50% reduction in death risk

The study authors noted these findings demonstrate associations, not causation, and the cohort was predominantly male (90%) with an average age of 65.

Weight Management and Long-Term Use

Weight Loss Efficacy

Individuals prescribed GLP-1 medications for weight loss have reported significant reductions. One source reported an average weight loss of approximately one-fifth of body weight among overweight individuals. A separate study of 7,938 patients in Ohio and Florida found those treated for obesity lost an average of 8.4% of their body weight while on medication.

Patterns of Discontinuation

Research indicates a substantial proportion of patients discontinue GLP-1 therapy. A JAMA research letter based on insurance claims data found that fewer than one in four patients remained on a GLP-1 medication after one year. A separate analysis suggested approximately half of all users discontinue within a year, with 75% stopping after two years.

Reasons for Discontinuation

A study published in Obesity by Cleveland Clinic researchers identified the following primary reasons:

Financial barriers were the most common reason across all time points, though side effects were more likely to lead to earlier discontinuation.

A separate Kantar survey found that 74% of people who had stopped taking GLP-1 drugs said they were likely or very likely to restart them.

Weight Regain and Health Outcomes After Discontinuation

Weight Regain

Meta-Analyses of Clinical Trials: A Cambridge University meta-analysis of 48 studies estimated that by 52 weeks after discontinuation, individuals had regained approximately 60% of the weight they initially lost, with the model projecting a plateau at roughly 75% of original weight loss.

A separate Oxford University meta-analysis of 37 studies found an average weight regain of 400 grams per month after medication cessation. This analysis projected that participants would return to their original weight within approximately 1.7 years, with a regain rate nearly four times faster than that observed in individuals who lost weight through diet and exercise alone.

Real-World Study: A Cleveland Clinic study of nearly 8,000 adults who used semaglutide or tirzepatide for 3–12 months found that among those treated for obesity, the average weight loss before stopping was 8.4%; one year later, they had regained an average of just 0.5%. This lower regain rate was attributed to many patients transitioning to other treatments: within 12 months, 27% switched to a different medication, 20% restarted their original medication, and 14% transitioned to intensive lifestyle programs.

Cardiovascular and Metabolic Effects

Reversal of Benefits: A study of over 333,000 U.S. veterans with type 2 diabetes, published in BMJ Medicine, found that patients who continuously took GLP-1s for three years demonstrated an 18% lower risk of heart attacks, strokes, or death compared to patients on sulfonylureas.

For those who discontinued GLP-1 treatment for at least six months, the study observed a 4% increase in heart risks compared to continuous users. A two-year interruption was associated with a 22% increase in risk, effectively erasing previously gained benefits. Improvements in blood pressure and cholesterol levels returned to pre-treatment levels within 1.4 years of cessation.

The Oxford meta-analysis found that positive cardiovascular and metabolic effects of GLP-1 medications are reversed if medication is discontinued. Diabetes and heart disease risks were predicted to return to pre-treatment levels within two years.

Adverse Effects and Management Strategies

Common Side Effects

Reported side effects include gastrointestinal issues such as nausea and constipation, described as primarily mild in clinical trials. Research also indicates that a significant portion of weight lost on GLP-1s can be lean muscle—as much as 40% of weight loss can be lean muscle, with weight loss typically consisting of about 40% muscle and 60% fat.

Prescribing Considerations

A functional medicine doctor has outlined five common errors in GLP-1 therapy management:

1. Starting medication without prior lifestyle changes
2. Starting without a thorough medical evaluation
3. Inadequate protein intake
4. Increasing the dose too quickly
5. Not proactively managing side effects

Clinical recommendations emphasize combining medication with lifestyle interventions, including nutritional changes and physical activity, for long-term weight management. Some experts suggest treatment may need to be lifelong due to the risk of weight regain and reversal of health benefits upon discontinuation.

Regulatory and Policy Context

• NHS Prescription: In the UK, Wegovy can be prescribed on the NHS for up to two years, while Mounjaro does not have a defined prescription time limit.
• Medicare: The pharmaceutical trade organization PhRMA is advocating for changes to Medicare rules to allow more patients access to GLP-1 drugs.
• Compounding Pharmacies: PhRMA is also pushing for increased oversight of compounding pharmacies that sell these medications directly to consumers.

Future Research

Researchers have indicated plans to study GLP-1s over longer durations and in larger, more diverse populations to confirm findings and assess long-term impacts. Further research is also planned to examine the comparative effectiveness of alternative treatment options for patients discontinuing these medications.