Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status

Abstract

Objective: The objective of this study was to characterize changes in body weight and glycated hemoglobin (in those with prediabetes at baseline) through 12 months by obesity pharmacotherapy discontinuation status.

Methods: This retrospective cohort study used electronic health record data from a large health system in Ohio and Florida to identify adults with overweight or obesity without type 2 diabetes who initiated injectable semaglutide or tirzepatide between 2021 and 2023. Treatment discontinuation was defined by a >90-day gap between exhaustion of previous supply and next dispense or end of study follow-up (December 2024) and was classified into early discontinuation (i.e., within 3 months of index date) and late discontinuation (i.e., within 3-12 months).

Results: We identified 7881 patients; 6109 received semaglutide, and 1772 received tirzepatide. A total of 80.8% had low maintenance dosages. Mean (SD) percentage weight reduction at 1 year was 8.7% (9.6%); and it was 3.6% (8.1%) with early discontinuation, 6.8% (9.1%) with late discontinuation, and 11.9% (9.2%) with non-discontinuation (p < 0.001). The mean (SD) absolute reduction in percent glycated hemoglobin at 1 year was 0.1 (0.4) with early discontinuation, 0.2 (0.4) with late discontinuation, and 0.4 (0.4) with non-discontinuation (p < 0.001).

Conclusions: The average weight reduction in this cohort was lower than that observed in the main phase 3 trials, likely because of higher rates of discontinuation and lower maintenance dosages.

FIGURE 1

Identification of eligible patients for inclusion. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Cumulative incidence of obesity pharmacotherapy discontinuation by index medication. A total of 7881 patients contributed to this analysis. Discontinuation of obesity pharmacotherapy was defined as a greater than 90‐day gap between exhaustion of previous supply and next dispense or between exhaustion of last supply and end of study follow‐up. Patients who switched between injectable forms of semaglutide, tirzepatide, or other obesity medications but had a gap of less than 90 days were not considered to have discontinued obesity pharmacotherapy. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Mean percentage weight reduction by (A) index medication and (B) obesity pharmacotherapy discontinuation status from initiation of the medication. A total of 7881 patients contributed to this analysis. Available weight measurements were captured from baseline through 12 months in 1‐month increments. Discontinuation of obesity pharmacotherapy at 1 year was defined as a greater than 90‐day gap between exhaustion of previous supply and next dispense or between exhaustion of last supply and end of study follow‐up. Patients who switched between injectable forms of semaglutide, tirzepatide, or other obesity medications but had a gap of less than 90 days were not considered to have discontinued obesity pharmacotherapy. Shaded areas indicate 95% CI. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Mean absolute change in glycated hemoglobin level (HbA1c) (percent) by (A) index medication and (B) obesity pharmacotherapy discontinuation status from initiation of the medication in patients with prediabetes at baseline. A total of 1320 patients contributed to this analysis. Available HbA1c level (percent) measurements were captured from baseline through 12 months in 1‐month increments. Discontinuation of obesity pharmacotherapy at 1 year was defined as a greater than 90‐day gap between exhaustion of previous supply and next dispense or between exhaustion of last supply and end of study follow‐up. Patients who switched between injectable forms of semaglutide, tirzepatide, or other obesity medications but had a gap of less than 90 days were not considered to have discontinued obesity pharmacotherapy. Shaded areas indicate 95% CI. [Color figure can be viewed at wileyonlinelibrary.com]