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GLP-1 receptor agonists (RAs) have transformed pharmacotherapy for obesity, representing a “paradigm shift” in treatment. According to a November 2025 report, nearly 1 in 5 US adults report having used GLP-1 RAs, including 12% who say they are currently taking one — a 6% increase from 18 months earlier.

“The stigma of being on a GLP-1 RA has decreased as more Americans are taking these medications,” Peminda Cabandugama, MD, director of digital obesity and faculty member in the obesity fellowship at Cleveland Clinic in Cleveland, told Medscape Medical News.

GLP-1 RAs are intended for long-term use, yet adherence remains “suboptimal.” A recently published retrospective analysis of 126,984 patients with overweight or obesity who initiated treatment with a GLP-1 RA between 2019 and 2024 found that persistence was low.

“Fewer than 1 in 4 patients remained on any GLP-1 RA after 12 months,” said lead author Luyu (Amber) Xie, PharmD, PhD, assistant professor at the School of Public Health, UT Southwestern Medical Center in Dallas.

Why Patients Start, and Stop, GLP-1 RAs

Although some patients are motivated by cosmetic weight loss, most seek GLP-1 RAs to improve health, said Gitanjali Srivastava, MD, professor of medicine, pediatrics, and surgery and medical director of clinical obesity medicine at Vanderbilt University Medical Center in Nashville, Tennessee.

“We see over 10,000 patients with obesity annually,” she told Medscape Medical News. “Many have struggled for years, eating healthy and exercising and doing everything to the dot. But their body isn’t responding, which is its way of telling them they need to take their obesity treatment to the next level. Many also have poor quality of life, joint aches and pains, or other health conditions.”

Cabandugama, a spokesperson for The Obesity Society, agreed that health concerns often drive treatment initiation, including diagnoses of cardiovascular disease, fatty liver, type 2 diabetes, and obstructive sleep apnea.

Both Srivastava and Cabandugama emphasized that cost is the leading reason patients discontinue treatment. Loss of insurance coverage or formulary changes can quickly make treatment unaffordable.

Side effects, particularly the common gastrointestinal (GI) complications, also contribute to discontinuation.

“Most can be managed fairly well with some simple interventions, but some patients don’t think of contacting their medical providers and simply discontinue treatment,” said Srivastava, who is also co-director of Vanderbilt Weight Loss Center.

Another contributor to discontinuation is unrealistic expectations.

“Patients may not realize that GLP-1 RAs have many different doses, and we often have to increase the dose before the medication reaches a therapeutic level,” she said. “If they don’t see an early effect, they may give up before it’s been given an adequate opportunity to work.”

Stopping and Restarting Therapy

Weight regain after GLP-1 RA discontinuation is common and often substantial, which may cause some patients to restart therapy.

“Claims data cannot fully capture why patients restart therapy,” Xie said. “But in clinical practice, weight regain, improved insurance coverage or medication availability, better tolerance after dose adjustment, or renewed motivation to continue treatment are likely factors.”

Cabandugama noted that patients in his practice typically restart once cost barriers are resolved, either with the same medication or switching to a different agent depending on coverage.

Srivastava added that patients often do better when restarting therapy.

“They tend to be more adherent the second time around and do pretty well,” she said.

Switching Between GLP-1 RAs

Switching between GLP-1 RAs is common and may improve adherence. Xie and colleagues found that about 1 in 5 patients switched agents within the first year.

“Patients who switched had higher 12-month persistence and adherence than those who didn’t switch, suggesting that switching may sometimes reflect active treatment management rather than treatment failure or disengagement from care,” Xie said.

The most common switch was from liraglutide to semaglutide, with injectable semaglutide frequently serving as both an initial therapy and subsequent option.

An earlier paper by some of the study’s co-authors outlined practical considerations for transitioning between GLP-RAs. It suggested that switching can be beneficial when patients experience insufficient weight loss, safety or tolerability issues, adherence challenges, insurance-related barriers, or a preference for a different dosing schedule.

In cases of GI intolerance, clinicians should confirm that all reasonable mitigating actions have been attempted before switching, such as ensuring the patient is taking the correct dose and using nonpharmacologic strategies to manage symptoms such as nausea.

When initiating a new GLP-1 RA, experts recommend avoiding high starting doses, even if the patient tolerated the previous agent well. Instead, the new therapy should begin at a lower dose with gradual titration. GI adverse events are common after switching, even among patients who did not experience them previously. These are typically transient and can be mitigated through slower dose escalation, smaller meal sizes, and lower-fat diets.

“When determining an appropriate strategy to increase adherence with injectable therapies, it is also important to consider the convenience of the dosing device,” the authors wrote. “Ready-to-use formulations and easy-to-use delivery systems such as single-dose prefilled pens and hidden, pre-attached needles may encourage patient acceptance.”

Comprehensive, Holistic Management

Cabandugama noted that the most successful patients are those who combine GLP-1 RA therapy with lifestyle changes such as a reduced-calorie diet and regular exercise.

“The whole experience of weight management needs to be done holistically,” he said.

GLP-1 RA therapy should be part of a broader, multidisciplinary, patient-centered obesity care plan. Xie described medication as a “powerful tool” but stressed that nutrition support, physical activity counseling, behavioral strategies, and mental health support are essential to sustaining long-term benefits.

She recommends early discussions to set patient expectations, including the need for long-term therapy.

“Clinicians should proactively discuss side effects, dose escalation, insurance and cost barriers, medication shortages, and what to do if therapy is interrupted,” she said.

Patients should be encouraged to focus on overall wellness, Srivastava added.

“They should nourish and nurture themselves, take care of stressors, and maintain healthy nutrition. The cleaner they feed their body, the better their body will operate.”

Regular follow-up is also critical. Srivastava encourages “touch points” throughout treatment, including visits with dietitians or trainers and monthly or bimonthly follow-ups to ensure accountability, particularly during active weight loss.

Once patients reach their target weight, the focus should shift to weight maintenance.

“It’s about learning and implementing the skills that the patient acquired over the past year to accomplish those goals,” she said. “Having a supportive structure, whether in the medical or community setting, is important to assuring the success of the patient.”

Xie and Cabandugama reported having no relevant financial relationships. Srivastava reported serving advisory roles with Eli Lilly, Novo Nordisk, Boehringer Ingelheim, Madrigal, Rhythm, and Quest Diagnostics. 

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom(the memoir of two brave Afghan sisters who told her their story).