GLP-1s are associated with an array of possible side effects that contribute to medication nonadherence and discontinuation among a significant portion of users, although most patients are able to tolerate them.

What spells the difference between adherence and nonadherence among patients who have unpleasant reactions? A new study suggests that experiencing the benefits of the drug (weight loss, reduced food cravings) can outweigh the negatives and motivate patients to put up with uncomfortable gastrointestinal (GI) side effects.

The researchers used “infoveillance” — publicly available online health data — to capture patient-centered perspectives that often don’t make their way into clinical trials.

“There has been enormous public discussion around GLP-1 drugs, but most of it focuses on celebrities, prescribing trends, or safety concerns,” senior author Morgan James, PhD, adjunct assistant professor of psychiatry at Robert Wood Johnson Medical School, Piscataway, New Jersey, told Medscape Medical News. “What has been largely missing is the patient perspective, or how people actually weigh the costs and benefits in their daily lives.”

The researchers analyzed 60 anonymous, publicly available reviews of Ozempic submitted to Drugs.com, a website that provides peer-reviewed and independent information on over 24,000 prescription drugs, over-the-counter medications, and natural products. Members of the public may submit open-ended reviews and quantitative ratings of products.

“We found that the single strongest factor determining whether people continue treatment is perceived effectiveness — whether they feel they are losing weight, eating less, or experiencing fewer cravings,” James said.

Although side effects such as nausea were “very frequent, they rarely drove people to stop treatment. Instead, people were much more likely to discontinue if the drug didn’t result in weight loss. In other words, patients were often willing to tolerate substantial discomfort as long as they believed the medication was helping them lose weight,” James said.

The researchers hope that by identifying the factors that drive adherence vs discontinuation, they “can better predict who will benefit, intervene earlier when treatment isn’t working, and support more informed decision-making for patients,” James said.

Which Factors Matter

Although not approved by the FDA for weight loss, Ozempic is often used off label for that purpose. The researchers searched Drugs.com for respondents who selected “weight loss” as the condition for which they were using Ozempic and analyzed 60 of 78 reviews from 2023.

Just over half of the respondents (55%) indicated that they experienced weight loss at some point during Ozempic treatment, 37% reported appetite suppression, and 13% reported decreased cravings — especially for sugary and greasy foods. In total, 67% reported reductions in weight, appetite, and/or cravings. On the other hand, 18% reported minimal or no weight loss or weight rebound.

Most respondents (80%) reported side effects that varied in nature and severity, with nausea and other GI complaints as the most common (62%). Nevertheless, these complaints did not significantly influence satisfaction ratings or decisions to continue treatment.

However, minimal/no weight loss and the emergence of non-GI physiologic side effects were associated with discontinuation of Ozempic treatment.

“The key clinical take-home message of our findings is that side effects alone do not predict adherence, but perceived benefit does,” James said.

Study Limitations

Commenting for Medscape Medical News, Tracy Norfleet, MD, MBA, spokesperson for the Obesity Society, said the study has “significant limitations.” Norfleet, an internal medicine, obesity, and lifestyle medicine specialist, BJC Health Care, St. Louis, said she would not rely on the study’s conclusions to guide clinical decision-making.

The “self-selected, anonymous sample of 60 online reviews from a single website cannot be considered representative of the broader population of patients using Ozempic,” she said. “The lack of demographic data, dosing information, treatment duration, and clinical verification of outcomes significantly undermines the validity of the findings.” For this reason, Norfleet doesn’t regard the findings as “clinically meaningful,” although they’re “loosely consistent” with her clinical experience.

The authors acknowledged these limitations and called for more research. “These findings provide a foundation for future structured studies aimed at improving adherence and optimizing treatment strategies for individuals with overweight and obesity,” they wrote.

Despite its limitations, the study is “interesting and creative” because it “analyzes publicly available online medication reviews to understand how patient perceive semaglutide in real-world use,” Reema Dbouk, MD, assistant professor of medicine, Emory University School of Medicine, Atlanta, told Medscape Medical News.

The study shows that “online patient-reported experiences can be a useful complementary data source for understanding medication adherence, expectations, and lived experience outside the structure of clinical trials,” added Dbouk, a spokesperson for The Obesity Society.

Managing GI Side Effects

Medical and obesity societies have worked together to develop guidance on preventing or mitigating the GI side effects of GLP-1s. Common recommendations include advising patients to maintain adequate hydration, eat smaller meals, reduce alcohol intake, and increase dietary fiber.

GI side effects are dose-dependent and typically settle once the dose stabilizes, noted a paper coauthored by members of several societies, including the Obesity Management Collaborative UK and the British Society of Lifestyle Medicine. For moderate-to-severe side effects, slower dose escalation, temporary dose reductions, or individualized target doses might be helpful. Short-term use of adjunctive medications, such as proton pump inhibitors or H2-antagonists for reflux and cyclizine for nausea, also may help.

Fiber supplements, osmotic laxatives, or stool softeners may help alleviate constipation, noted an advisory by the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society.

Patient education and counseling are critical, James said. “Rather than pointing to a specific dosing strategy, our work suggests a communication strategy: Regularly evaluate treatment response, set expectations around manageable side effects, and reconsider treatment early if the medication is not producing a noticeable effect for that individual,” he advised.

Conversations with patients should focus not only on managing nausea or GI symptoms but also on expectations, including what a meaningful response looks like, when it can be expected, and what to do if it doesn’t occur, he added.

Conversations about setting expectations and symptom management should take place even before treatment is initiated, Dbouk said.

Norfleet said that practicing clinicians should spend more time educating patients on the appropriate FDA on-label use of Ozempic, which is approved for glycemic control for people with type 2 diabetes.

“Clinicians should reinforce that obesity is a chronic disease and GLP-1s are not indicated and should not be prescribed for cosmetic weight-loss purposes,” she said.

For patients taking these agents, clinicians should engage in “frequent and continuous monitoring for adverse side effects” and educate patients on how to recognize and report them, she said.

The research was funded by grants to James from the University of Sydney; the National Institute on Drug Abuse; the National Heart, Lung, and Blood Institute; Rutgers Optimizes Innovation; the New Jersey Health Foundation; and Rutgers Global. James reported being an inventor on patent PCT/US23/27918 titled “Therapeutic combinations and methods,” which describes novel approaches for reducing overeating. Two study authors acknowledged support through stipends from the National Science Foundation. The other authors reported having no relevant financial relationships. Norfleet reported being a member of the speakers bureau, on advisory board for Currax Pharmaceuticals, Eli Lilly, and Novo Nordisk, and a contributing writer to GoodRx. Dbouk reported having no relevant financial relationships.

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).