Study Assesses Weight Reduction and Glycemic Status With GLP-1 Medications

Injectable glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide (Ozempic, Wegovy, Rybelsus; Novo Nordisk) and tirzepatide (Mounjaro, Zepbound; Eli Lilly and Company), were reported to produce smaller weight loss in a real-world setting compared with randomized clinical trials. The study authors, who published their findings in the Obesity Journal, noted this was due to patients discounting treatment or using lower maintenance dosages, which led to negative impacts on blood sugar control for individuals with prediabetes.^1,2

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GLP-1s For Weight Management

Obesity and type 2 diabetes (T2D) are closely related conditions that increase the risk of cardiovascular disease. Individuals with obesity are 6 times more likely to develop diabetes caused by an overproduction of glucose, which could lead to diabetes worsening faster; however, not all individuals with obesity are guaranteed to get diabetes, because other factors such as family history, diet, exercise, stress, and gut health are also closely related.³

As FDA-approved treatments for T2D and chronic weight management, semaglutide and tirzepatide have demonstrated significant weight reductions in randomized clinical trials among individuals with obesity compared to other FDA-approved obesity treatments. While it is known that treatment discontinuation is common among individuals receiving either semaglutide or tirzepatide, there is a lack of research on its impact on weight reduction and glycemic control in clinical practice.^1,2

GLP-1s in Real-World Settings

To assess the impact of injectable GLP-1s in a real-world setting, researchers from Cleveland Clinic conducted a retrospective cohort study that evaluated weight reduction and blood sugar regulation among 7881 individuals with an average body mass index (BMI) greater than 39, which indicates clinically severe obesity. Of the total participants, 6106 filled an initial prescription for semaglutide and 1772 filled one for tirzepatide from January 1, 2021, to December 31, 2023. Individuals' mean age was 51.3 years, with a mean baseline weight of 112.2 kg and a mean baseline BMI of 39.7. Most individuals were female (n = 5923), and 1958 were male. Additionally, at the start of the study, 1320 participants had prediabetes, which was defined as blood sugar levels between 5.7% and 6.4%.¹

The study’s primary outcomes were percentage body weight reduction and, for prediabetic patients, absolute Hb_A1c reduction over 12 months. Patients needed baseline data and at least 1 follow-up measurement between 30 and 365 days for inclusion within monthly follow-ups. Secondary outcomes included achieving 10% or greater weight loss at 1 year, and for prediabetic patients, their glycemic status at 1 year.¹

The results demonstrated that more than 20% of individuals discontinued their medications early, and 32% discontinued their medications late, mostly due to the costs of the medications, insurance coverage-related issues, adverse effects, and medication shortages. Additionally, about 80.8% of individuals had low maintenance dosages that were equal to or less than 1 mg for semaglutide and equal to or less than 7.5 mg for tirzepatide.¹

Results following 1 year after the start of the treatment demonstrated a mean percentage weight reduction of 8.7%, with 3.6% in individuals who discontinued treatment early compared with 6.8% in individuals who discontinued treatment late.^1,2

“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 randomized clinical 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,” Hamlet Gasoyan, PhD, lead study author and researcher with Cleveland Clinic’s Center for Value-Based Care Research, said in a news release.²

REFERENCES

1. Gasoyan H, Butsch WS, Schulte R, et al. Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. Obesity (Silver Spring). 2025; 1-11. doi:10.1002/oby.24331

2. Cleveland Clinic research finds injectable medications for obesity produce smaller weight loss in a real-world setting, compared to randomized clinical trials. EuerkAlert!. News release. June 10, 2025. Accessed July 8, 2025. https://www.eurekalert.org/news-releases/1086406

3. Diabesity: How Obesity Is Related to Diabetes. Cleveland Clinic. News release. November 8, 2021. Accessed July 8, 2025. https://health.clevelandclinic.org/diabesity-the-connection-between-obesity-and-diabetes