Weight-loss injections such as semaglutide and tirzepatide—hailed for their effectiveness in clinical trials—are proving less successful in everyday clinical use, according to a new study by the Cleveland Clinic. The research highlights that medication discontinuation, dosage variations, and cost barriers significantly impact results.
These drugs, initially developed to treat type-2 diabetes and later approved for chronic weight management, helped participants in controlled studies shed substantial weight. However, the Cleveland Clinic’s analysis of real-world data suggests a more modest outcome when patients are outside the strict structure of clinical trials.
“Our study shows that patients treated for obesity with semaglutide or tirzepatide lost less weight on average in a regular clinical setting compared to what is observed in randomised clinical trials,” said lead author Hamlet Gasoyan, PhD. “According to our data, this could be explained by higher rates of discontinuation and lower maintenance dosages used in clinical practice, compared to randomised clinical trial settings.”
Published in the Obesity Journal, the study tracked 7,881 adults with a body mass index (BMI) over 39, who began weight-loss injections between 2021 and 2023. Over 20% of these patients stopped taking the drugs early, while another 32% discontinued later, reports Belfast Live.
Weight loss outcomes varied based on how long patients stayed on the medication. Those who stopped early lost just 3.6% of their body weight over a year, while those who discontinued later lost about 6.8%. In contrast, patients who adhered to their treatment saw significantly better results, losing an average of 11.9% of their body weight.
The study identified multiple factors behind treatment discontinuation. High out-of-pocket costs and insurance limitations were the most common reasons, followed by side effects and drug availability.
“Our findings about the real-world use patterns of these medications and associated clinical outcomes could inform the decisions of healthcare providers and their patients on the role of treatment discontinuation and maintenance dosage in achieving clinically meaningful weight reductions,” Dr. Gasoyan explained.
Researchers also found that sticking with a high maintenance dose and not stopping too early or too late were key to better results. Gender also played a role—female patients were more likely to experience greater weight loss. Additionally, users of tirzepatide saw slightly better outcomes than those using semaglutide.
The findings highlight the gap between controlled environments and real-world medical practice, suggesting that while these drugs are powerful tools, their success depends heavily on sustained access, proper dosing, and patient commitment.