A recent study highlights the importance of medication adherence for significant weight loss and improved glycemic control in obesity treatment with GLP-1 agonists.
Hamlet Gasoyan, PhD
Photo courtesy of The Cleveland Clinic
A new study underscores the critical role of medication adherence in achieving substantial weight loss and glycemic improvements with GLP-1 receptor agonists for obesity management.
In a large retrospective cohort clinical trial of 7881 adults treated for obesity in routine clinical practice, patients who remained on injectable semaglutide or tirzepatide therapy for a full year experienced significantly greater weight reduction and glycemic improvement than those who discontinued treatment early.
"Treatment discontinuation is common among patients receiving tirzepatide or semaglutide for obesity, but little is known regarding its impact on weight reduction and glycemic control in clinical practice," first author Hamlet Gasoyan, PhD, health services researcher in the department of internal medicine and geriatrics and investigator at the Center for Value-Based Care Research at Cleveland Clinic and assistant professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and colleagues wrote in the journal Obesity.
The study included adults aged 18 years or older with obesity without type 2 diabetes from Cleveland Clinic in Ohio and Florida who initiated subcutaneous semaglutide or tirzepatide from 2021 to 2023. Treatment discontinuation was defined as a gap of more than 90 days between the end of the previous medication supply and the next dispense or the end of the study follow-up in December 2024. The primary outcome was percentage change in body weight from drug initiation to 1 year. Change in HbA1c from baseline to 1 year was a second primary outcome for adults with prediabetes at baseline, according to the study.
There were 7881 adults included in the study (mean age, 51.3 years; 75.2% women), of whom 6109 were prescribed semaglutide and 1772 were prescribed tirzepatide.
Of the semaglutide group:
Of adults prescribed tirzepatide:
Among 6 477 adults with weight measurements available at 1 year, mean weight loss was 11.9% for those who did not discontinue therapy, compared to 6.8% for those with late discontinuation and 3.6% for those who stopped within 3 months (P < .001).
Tirzepatide was associated with greater mean weight reduction than semaglutide—12.4% vs 7.7% at 1 year. Among patients who remained on tirzepatide and were on high-dose maintenance therapy, mean weight loss reached 18%.
In adjusted models, odds of achieving ≥10% weight loss at 1 year were significantly higher among patients who continued therapy (adjusted odds ratio [aOR], 4.68), were prescribed tirzepatide vs semaglutide (aOR, 2.46), or were on high vs low maintenance doses (aOR, 2.39). Female sex was also associated with increased odds (aOR, 1.86).
Among 895 adults with prediabetes at baseline, mean HbA1c reduction at 1 year was 0.4 percentage points for those who continued therapy, compared with 0.2 and 0.1 percentage point reductions in the late and early discontinuation groups, respectively (P < .001). At 1 year, 67.9% of those who remained on therapy achieved normoglycemia, compared with 41% and 33.1% in the late and early discontinuation groups.
Type 2 diabetes was diagnosed in 3.4% of the cohort at 1 year, with incidence highest among those who discontinued therapy within 3 months (6.5%) and lowest among those who continued treatment (1.7%).
Investigators concluded that persistence with obesity pharmacotherapy and appropriate dose escalation are key to achieving outcomes comparable to those reported in clinical trials.
"Our findings could inform the decisions of healthcare providers and their patients on the role of treatment discontinuation and maintenance dosage in achieving clinically meaningful weight loss," researchers concluded.
Source: Gasoyan H, Butsch WS, Casacchia NJ, et al. Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. Obesity. Published online June 10, 2025. doi:10.1002/oby.24331
