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A Cleveland Clinic research exhibits that semaglutide and tirzepatide—injectable GLP-1 medication for weight problems—produce smaller weight reduction in a real-world setting as a result of sufferers discontinue therapy or use decrease upkeep dosages. Therapy discontinuation additionally negatively impacted blood sugar management in sufferers with prediabetes. The research was revealed within the Weight problems Journal.
Hamlet Gasoyan, Ph.D., lead writer of the research and a researcher with Cleveland Clinic’s Middle for Worth-Primarily based Care Analysis, mentioned, “Our research exhibits that sufferers handled for weight problems with semaglutide or tirzepatide misplaced much less weight on common in an everyday medical setting in contrast to what’s noticed in randomized medical trials.
“According to our data, this could be explained by higher rates of discontinuation and lower maintenance dosages used in clinical practice, compared to randomized clinical trial settings.”
Semaglutide (offered below the model names Wegovy and Ozempic) and tirzepatide (offered below the model names Zepbound and Mounjaro) are FDA-approved medicines for the therapy of kind 2 diabetes and continual weight administration.
Whereas randomized medical trials have proven the efficacy of these medicines, Dr. Gasoyan and colleagues studied their impact on weight discount and blood sugar regulation (glycemic management) in a real-world setting.
This Cleveland Clinic retrospective cohort research included 7,881 grownup sufferers with a mean physique mass index (BMI) larger than 39, which is classed as clinically extreme weight problems. Among the many contributors, 1,320 had pre-diabetes at the beginning of the research, outlined by blood sugar ranges between 5.7–6.4%. Sufferers who’ve pre-diabetes are at the next threat of creating kind 2 diabetes, which is likely one of the most typical problems of weight problems.
The research contributors started therapy for weight problems with injectable types of semaglutide or tirzepatide between 2021 and 2023. Researchers grouped sufferers who discontinued their weight problems medicines into those that discontinued early (inside three months) and late (inside three to 12 months). The research’s follow-up resulted in December 2024.
Researchers discovered that greater than 20% of sufferers discontinued their medicines early and 32% discontinued their medicines late. As well as, greater than 80% of research contributors have been on decrease upkeep dosages of these medicines (i.e., equal to or lower than 1 mg for semaglutide and equal to or lower than 7.5 mg for tirzepatide). The upkeep dose refers back to the quantity of treatment wanted to maintain a therapeutic impact.
One yr after the beginning of the therapy, researchers discovered that the common weight discount was 3.6% among the many contributors who discontinued their therapy early, in comparison with 6.8% for many who discontinued their therapy late. Those that didn’t discontinue therapy misplaced on common 11.9% physique weight.
Those that didn’t discontinue therapy and have been on excessive upkeep dosage of the medicines misplaced 13.7% of their physique weight with semaglutide and 18.0% with tirzepatide.
“Our findings about the real-world use patterns of these medications and associated clinical outcomes could inform the decisions of health care providers and their patients on the role of treatment discontinuation and maintenance dosage in achieving clinically meaningful weight reductions,” mentioned Dr. Gasoyan.
Researchers additionally recognized what components have been related to greater odds of attaining weight lack of 10% or extra, which offers clinically important well being advantages on this affected person inhabitants. Sufferers had greater odds of attaining 10% or larger weight discount after one yr of therapy in the event that they:
didn’t discontinue their medicines or discontinued late (vs. early)
have been on excessive upkeep dosage
acquired tirzepatide (vs. semaglutide)
have been feminine (vs. male).
Along with wanting on the components that have an effect on an individual’s weight trajectory, researchers tracked glycemic management in sufferers who had pre-diabetes at the beginning of the research.
Among the many contributors with pre-diabetes, 33% of those that discontinued their therapy early skilled regular blood sugar ranges (outlined by an HbA1c degree of 5.6 or decrease), in comparison with 41% who discontinued their therapy late, and 67.9% who didn’t discontinue therapy.
“In our study, the majority of the patients with pre-diabetes experienced normal blood sugar levels when they continued their treatment,” mentioned Dr. Gasoyan. “Type 2 diabetes is one of the most common complications of obesity, so diabetes prevention is very important. This study highlights that treatment discontinuation, especially early, negatively affects both weight and glycemic control outcomes.”
The most typical causes for discontinuation of therapy included the price of the medicines and insurance coverage protection–associated points, unwanted effects, and drugs shortages. A follow-up research is within the works to quantify why sufferers discontinue their weight problems medicines in a real-world setting.
As well as, researchers noticed that whereas sufferers who discontinued weight problems medicines misplaced considerably much less weight in comparison with those that endured, their weight trajectories remained comparatively steady.
This will likely be studied additional to establish what extra weight administration strategies sufferers are utilizing in actual world settings after discontinuation of weight problems medicines.
Extra info:
Adjustments in weight and glycemic management following weight problems therapy with semaglutide or tirzepatide by discontinuation standing, Weight problems (2025). DOI: 10.1002/oby.24331
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Cleveland Clinic
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Injectable medicines for weight problems discovered to provide smaller weight reduction in a real-world setting (2025, June 10)
retrieved 10 June 2025
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