GLP-1 Persistence for Weight Loss Nearly Doubles in Recent Years

In patients without diabetes being treated with GLP-1 receptor agonists (GLP-1s) for overweight or obesity, GLP-1 persistence rates—the proportion of patients remaining on therapy without gaps exceeding 60 days—have significantly improved over the last five years. Results from two new studies underscore this encouraging trend, providing real-world evidence on how these high-potency weight loss medications are being used more consistently.

"This real-world analysis of high-potency, weight loss-indicated GLP-1 products among individuals without diabetes found that 1-year treatment persistence has nearly doubled from 2021 to the first half of 2024," reported the authors of the first study, recently published in the Journal of Managed Care & Specialty Pharmacy.

Understanding Persistence in GLP-1 Therapy for Weight Loss

GLP-1 receptor agonists, such as semaglutide (found in Wegovy and Ozempic) and tirzepatide (Mounjaro and Zepbound), mimic the glucagon-like peptide-1 hormone. This action slows gastric emptying, reduces appetite, and promotes satiety, leading to substantial weight loss—often 15-20% of body weight in clinical trials. For patients without diabetes, these drugs are increasingly prescribed for obesity management, but long-term success hinges on GLP-1 persistence.

Persistence is defined as continuous therapy without gaps longer than 60 days, distinct from adherence, which measures the proportion of days covered by medication. Gaps don't always mean discontinuation; patients might source drugs out-of-pocket from manufacturers or compounding pharmacies during insurance lapses, as noted by first author Landon Z. Marshall, PharmD, PhD, of Prime Therapeutics in Eagan, Minnesota.

Data from the Prime Therapeutics Database

Marshall and colleagues analyzed data from the Prime Therapeutics database for 33,607 insured patients without diabetes who initiated GLP-1 treatment with semaglutide or tirzepatide between January 2021 and June 2024. Of these, 75.5% were female, with a mean age of 45.7 years.

Overall 1-year persistence rates nearly doubled, from 33.2% in 2021 to 60.9% in the first half of 2024. Breaking it down:

• Semaglutide: 33.2% in 2021, 34.1% in 2022, 39.8% in 2023, and 58.6% by mid-2024.
• Tirzepatide: Starting in 2023 at 64%, rising slightly to 64.8% by mid-2024.

"To our knowledge, this is the first study to assess persistence, adherence, and switching among individuals initiating GLP-1 weight-loss products as recently as the first half of 2024," the authors noted, emphasizing the contemporary mix of high-potency agents.

Adherence also improved, reaching 55.5% in mid-2024 initiators versus 30.2% in 2021. This doubling suggests fewer discontinuations and better regular use, driven by resolved supply shortages and enhanced patient management.

Trends in Switching GLP-1 Medications

The second study, published in JAMA Network Open, examined 126,984 patients without diabetes from the Merative MarketScan Commercial Claims and Encounters Database. These overweight or obese individuals, enrolled between 2019 and 2024 after at least 12 months of continuous coverage, showed 20.6% switched GLP-1 agents within 12 months, with overall persistence at 24.6%.

The most common switch was liraglutide to semaglutide (24.4% of transitions). Notably, switchers had higher persistence (36.4% vs. 21.4% for nonswitchers), adherence (63% vs. 52% proportion of days covered), and optimal adherence (≥80% days covered: 33.3% vs. 28.6%; P < .001 for both).

"Switching between GLP-1 agents was common and may reflect active therapy management rather than nonengagement, particularly as new formulations and weight management agents emerge," wrote lead author Sarah E. Messiah, PhD, of The University of Texas Southwestern Medical Center, Dallas. "In this large cohort of adults with overweight or obesity without diabetes, fewer than 1 in 4 patients remained on any GLP-1 after 12 months."

The authors advocate reframing switching as optimization: "Clinicians should encourage continuity across switches and address coverage, cost, and adverse effect barriers that limit persistence."

Factors Driving Improved GLP-1 Persistence

Key drivers include the resolution of semaglutide and tirzepatide shortages, which plagued early adoption, and better clinical practices. Marshall highlights clinicians' roles: developing comprehensive obesity plans with diet, exercise, side effect preparation (e.g., nausea, gastrointestinal issues), structured follow-ups, and lifestyle reinforcement.

Common side effects like nausea, vomiting, and diarrhea often peak early but wane; dose titration helps. Cost and coverage remain barriers, but insurance expansions for obesity have helped. Tools like apps for symptom tracking—such as Shotlee for logging side effects and schedules—can support adherence without adding burden.

Expert Commentary on Persistence Rates

Arya M. Sharma, MD, professor emeritus at the University of Alberta, called the trends "very encouraging." "Like treatment of every other chronic disease, it's not realistic to expect persistence figures to go up to 100%, but the 50% to 60% [observed in the research] is not so bad."

Higher persistence among switchers aligns with engagement: "If you switch, it does indicate that you're willing to continue." Discontinuation risks weight regain, so switching for better tolerance or efficacy is preferable. Sharma consults for Novo Nordisk and Lilly; Marshall is with Prime Therapeutics.

Clinical Implications and Patient Guidance

These findings matter because sustained GLP-1 use prevents weight regain, reduces obesity-related risks like cardiovascular disease and type 2 diabetes. Compared to older agents like liraglutide (lower persistence historically), semaglutide and tirzepatide show superior profiles.

Patients should:

• Discuss eligibility (BMI ≥30 or ≥27 with comorbidities) with providers.
• Start low-dose, titrate slowly to minimize GI side effects.
• Combine with 500-calorie deficit diet and 150+ minutes weekly exercise.
• Monitor via regular check-ins; consider switching if side effects persist.
• Explore coverage options; compounding may bridge gaps.

Key Takeaways for GLP-1 Persistence in Weight Loss

• 1-year persistence nearly doubled to 60.9% by mid-2024.
• Tirzepatide edges semaglutide in early persistence.
• Switching boosts outcomes, signaling active management.
• Clinicians: Focus on holistic plans, side effect mitigation.
• Patients: Persistence yields lasting benefits; address barriers proactively.

In conclusion, rising GLP-1 persistence for weight loss reflects maturing therapy amid supply stability and better support. Patients and providers can build on this for optimal metabolic health outcomes. Related topics: GLP-1 Side Effects Management, Tirzepatide vs. Semaglutide Comparison.