A new study published in the Journal of Medical Internet Research provides important insights into how individuals using semaglutide off-label for weight loss perceive its benefits and adverse effects, and what ultimately drives treatment continuation or discontinuation. By analyzing user-generated reviews on an online medication platform, investigators found that perceived weight-loss effectiveness exerts a substantially greater influence on patient satisfaction and persistence than the burden of commonly reported side effects.
Obesity remains a chronic, relapsing metabolic disease associated with increased risks of cardiovascular disease, type 2 diabetes mellitus, and certain cancers. Since 1990, global prevalence has more than doubled, intensifying demand for effective and sustainable interventions. Although lifestyle modification remains the recommended first-line strategy, long-term adherence and clinically meaningful weight reduction remain challenging for many patients. Bariatric surgery offers substantial and durable weight loss but carries surgical risks and is not feasible or acceptable for all individuals. In this context, glucagon-like peptide-1 receptor agonists have emerged as a transformative pharmacologic option.
Semaglutide is indicated for type 2 diabetes mellitus and chronic weight management. It improves glycemic control through glucose-dependent insulin secretion and glucagon suppression, delays gastric emptying, and acts centrally on appetite-regulating pathways. Clinical trials have demonstrated mean body-weight reductions ranging from approximately 7.9% to 17.3%, along with improvements in HbA1c, waist circumference, and systolic blood pressure. However, gastrointestinal adverse events are common and have been reported in 42% to 83% of participants. Nausea, vomiting, constipation, and diarrhea are the most frequent. Gallbladder complications and other adverse effects have also been described, creating a clinical balance between efficacy and tolerability.
To better understand how patients weigh these trade-offs outside controlled trial settings, researchers conducted an infoveillance study combining qualitative thematic analysis with quantitative modeling. Sixty user reviews posted on Drugs.com between February and June 2023 were analyzed. The dataset included narrative descriptions and effectiveness ratings but lacked demographic data and clinical verification regarding dosing, comorbidities, or duration of therapy.
Weight-related outcomes dominated user perceptions. Approximately two-thirds of reviewers reported reductions in appetite, cravings, or body weight, and more than half described measurable weight loss during treatment. These users tended to assign high satisfaction scores, with a median rating of 8.5 out of 10. Many narratives emphasized appetite suppression and reduced cravings for calorie-dense foods as meaningful benefits. In contrast, nearly one in five users reported minimal weight loss or weight regain. Some described early improvement followed by plateauing or reversal, a pattern consistent with longer-term clinical observations.
Despite the high prevalence of adverse effects, around 80% of reviewers reported non-weight-related symptoms and approximately 62% described gastrointestinal complaints. Tolerability did not significantly influence satisfaction scores or decisions to continue therapy. Users intending to persist with treatment reported similar rates of gastrointestinal symptoms as those planning discontinuation. Perceived effectiveness emerged as the primary determinant of satisfaction and continuation. Ratings were notably polarized, with more than half of respondents assigning either the lowest or highest possible score.
The findings suggest that in real-world off-label use, demonstrable weight loss outweighs tolerability concerns for many individuals. Patients appear willing to endure nausea or other gastrointestinal discomfort if meaningful weight reduction is achieved. In contrast, perceived inefficacy or weight-loss plateau often prompts discontinuation even in the absence of severe adverse events. These patient-reported experiences provide complementary insight into behavioral drivers of adherence and underscore the importance of setting realistic expectations about both the magnitude and trajectory of weight loss when prescribing glucagon-like peptide-1 receptor agonists.
Reference
- Armanious AJ, Hunter RM, Griffiths KR, Bowrey HE, Brown RM, James MH. Patient Perceptions of Ozempic (Semaglutide) for Weight Loss: Mixed Methods Analysis of Online Medication Reviews. J Med Internet Res. 2026 Jan 9;28:e78391.