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Semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed clinical expectations for obesity treatment by producing substantial and sustained weight loss in many patients. Yet a large population-wide study from Denmark presented at the European Association for the Study of Diabetes (EASD) shows a stark gap between clinical promise and real-world use: more than 50% of adults without diabetes who started semaglutide discontinued it within one year.
Study design and data sources
Researchers used national health registries to identify all adults (aged 18+) in Denmark who initiated semaglutide for weight loss between the drug's national launch on 1 December 2022 and 1 October 2023. The analysis captured prescription fill patterns for 77,310 first-time semaglutide users without diabetes, enabling population-level estimates of discontinuation at 3, 6, 9 and 12 months after initiation.
By one year, 40,262 people (median age 50; 72% women) were no longer taking semaglutide. Discontinuation rates were 18% at 3 months, 31% at 6 months and 42% at 9 months, culminating in a >50% dropout by 12 months.
Key findings: who discontinues and why
The investigators identified several factors that increased the likelihood of stopping semaglutide within the first year:
- Younger age: Adults aged 18–29 were 48% more likely to stop than those aged 45–59 (adjusted for sex).
- Low-income areas: People living in lower-income neighborhoods were 14% more likely to discontinue than those in higher-income areas.
- Prior gastrointestinal medication use: A proxy for vulnerability to gastrointestinal adverse effects (nausea, vomiting, diarrhea) predicted a 9% higher discontinuation rate.
- Psychiatric and chronic conditions: People with prior psychiatric medication use were 12% more likely to stop; those with cardiovascular disease or other chronic illnesses were ~10% more likely to discontinue.
- Sex differences: Men were 12% more likely to stop treatment within a year than women.
Cost emerged as a major practical barrier: as of June 2025, the lowest-dose semaglutide cost roughly €2,000 per year in Denmark, a price that likely contributes to higher dropout among younger adults and people in low-income areas.
Scientific background and clinical context
GLP-1 receptor agonists like semaglutide act on receptors in the gut and brain to reduce appetite and enhance feelings of fullness (satiety). Originally developed to treat type 2 diabetes, these drugs showed collateral benefits on body weight that prompted regulatory approvals for obesity indications. However, the mechanism that controls appetite while on therapy does not necessarily reprogram long-term energy balance. Evidence indicates weight often returns after drug cessation, which means sustained benefit typically requires continued dosing.
Professor Reimar W. Thomsen, lead author and epidemiologist at Aarhus University, emphasized the clinical implication: "This level of drop off is concerning because these medications aren't meant to be a temporary quick fix. For them to work effectively, they need to be taken long term. All of the beneficial effects on appetite control are lost if the medication is stopped."
Adverse effects and equity concerns
Gastrointestinal side effects — nausea, vomiting and diarrhea — are commonly reported early in therapy and appear to contribute to discontinuation, as suggested by the association with prior GI medication use. The study also highlights equity risks: high out-of-pocket costs can widen health disparities because obesity prevalence is higher in marginalized racial, ethnic and socio-economic groups who may have less access to long-term pharmacotherapy.
Limitations of the analysis
The authors note registry-based limits: individual BMI and exact weight-loss outcomes were not available, nor were details on private insurance coverage or patient out-of-pocket payments. Milder adverse effects or subjective reasons for stopping (e.g., perceived insufficient weight loss, pregnancy planning, medication preferences) are under-captured in prescription registers. These gaps mean the true mix of clinical, social and financial drivers of discontinuation may be broader than registry data show.
Implications and future directions
High early discontinuation has multiple implications. Clinically, stopping semaglutide often results in weight regain, negating earlier gains. From a public-health perspective, wasted early treatment episodes increase cost burden without delivering sustained benefit. Policy responses could include negotiated pricing, reimbursement strategies that reduce out-of-pocket cost, and integrated care models that pair pharmacotherapy with behavioural, dietary and mental-health support to improve persistence.
Expert Insight
"Sustained outcomes from GLP-1 therapies depend on more than the drug itself," says Dr. Elena Martín, a clinical obesity specialist who was not involved in the study. "We need adherence strategies that address side effects, realistic expectations about weight trajectories, and the financial barriers many patients face. Combining pharmacotherapy with structured follow-up — including dose titration, symptom management and psychosocial support — may reduce early dropouts and improve long-term results."
Conclusion
The Danish registry study provides robust, population-level evidence that more than half of adults without diabetes discontinue semaglutide within a year. Cost, gastrointestinal side effects, psychiatric and chronic comorbidities, and demographic factors such as younger age and male sex all contribute to early discontinuation. Because weight regain commonly follows treatment cessation, improving long-term adherence through policy changes, clinical support and better access will be essential to realize the full public-health potential of GLP-1RAs in obesity care.
Source: sciencedaily
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