Time-Efficacy Relationship of Semaglutide in the Treatment of Type 2 Diabetes Mellitus: A Model-Based Meta-Analysis

Objective: Our objective was to quantify the efficacy of subcutaneous once-weekly semaglutide in treating type 2 diabetes mellitus (T2DM) over time.

Methods: Based on a literature search of the PubMed, Embase, Cochrane, and Web of Science databases, a modified maximum effect (E_max) model including rebound effects was built using model-based meta-analysis with change from baseline in glycated hemoglobin as the efficacy endpoint. This was combined with the covariate model to form a final model, and then theoretical values of E_max and time to reach 50% of E_max (ET₅₀) were obtained for each dose. Model fit and prediction were assessed using goodness-of-fit plots and visual prediction checking.

Results: E_max and ET₅₀ were influenced by the proportion of males and the baseline values, respectively. There was no evidence of a placebo effect with semaglutide. The efficacy of other doses became more significant over time, and a rebound effect was observed after maximum efficacy, at a rate of 0.018. Simulation of the typical efficacy at the different doses yielded a maximum efficacy of -1.58% with 0.5 mg and a maximum efficacy of -1.87% with 1 mg. In addition, the six simulated doses (0, 0.1, 0.2, 0.5, 1, and 2 mg) showed a dose-dependent relationship between dose and efficacy except for 0.4 mg and 0.8 mg. A higher dose would result in greater efficacy and a faster onset of action.

Conclusion: The efficacy of semaglutide in glucose control was investigated using the model-based meta-analysis method, which yields new insights into the treatment of T2DM with semaglutide.