IMPACT OF BASELINE CLINICAL CHARACTERISTICS ON WEIGHT LOSS OUTCOMES WITH INCRETIN-BASED THERAPIES: A MULTIVARIATE META-REGRESSION ANALYSIS
Author(s)
Sujoy Ghosh, MD, DM1, Prabhakar Pandey, M.Pharm, MBA2, Rishabh D. Pandey, PhD2;
1Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Researc, Kolkata, India, 2SEREXIA CONSULTANCY PVT LTD, Bengaluru, India
1Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Researc, Kolkata, India, 2SEREXIA CONSULTANCY PVT LTD, Bengaluru, India
OBJECTIVES: While incretin-based therapies have demonstrated significant efficacy in weight reduction, the influence of baseline metabolic profiles on the magnitude of this effect remains complex. This study aimed to identify clinical predictors of weight loss response using meta-regression, specifically examining how initial body weight and glycemic status moderate treatment outcomes in obesity management.
METHODS: A systematic review and multi-level meta-regression analysis (MLMA) of randomized controlled trials (RCTs) that evaluated semaglutide, liraglutide, and tirzepatide was conducted. All dosages were included, with placebo as the comparator. The MLMA model was employed to correct for dependent comparisons in multi-arm trials that use a single placebo group. Analyses were stratified by population (T2D vs. non-diabetic) and outcome (glycemic control vs. weight management).
RESULTS: For weight management in non-diabetic populations, tirzepatide and semaglutide were associated with an additional mean weight reduction of approximately 17.34 kg and 7.06 kg, respectively, compared to the liraglutide reference (p<0.0001). Higher baseline body weight was a significant moderator, predicting greater weight loss (β=−0.2230, p=0.0120). In the T2D population, tirzepatide was associated with an additional 5.34 kg weight reduction versus liraglutide (p<0.0001), while semaglutide showed no significant difference. Higher baseline weight also predicted modest additional weight loss in T2D individuals (β2=-0.1159, p=-2.0177). Regarding glycemic control in T2D, tirzepatide was associated with an HbA1c reduction of approximately 0.8% compared to liraglutide (p<0.0001), while semaglutide demonstrated a non-significant trend. Baseline HbA1c and follow-up duration were not significant moderators for glycemic control.
CONCLUSIONS: The analysis showed tirzepatide was associated with significant reductions in both body weight and HbA1c. Baseline body weight was identified as a key predictor for the magnitude of weight loss in both non-diabetic and T2D populations. The MLMA methodology provided a mathematically conservative and reliable estimate for these complex, multi-arm trial data.
METHODS: A systematic review and multi-level meta-regression analysis (MLMA) of randomized controlled trials (RCTs) that evaluated semaglutide, liraglutide, and tirzepatide was conducted. All dosages were included, with placebo as the comparator. The MLMA model was employed to correct for dependent comparisons in multi-arm trials that use a single placebo group. Analyses were stratified by population (T2D vs. non-diabetic) and outcome (glycemic control vs. weight management).
RESULTS: For weight management in non-diabetic populations, tirzepatide and semaglutide were associated with an additional mean weight reduction of approximately 17.34 kg and 7.06 kg, respectively, compared to the liraglutide reference (p<0.0001). Higher baseline body weight was a significant moderator, predicting greater weight loss (β=−0.2230, p=0.0120). In the T2D population, tirzepatide was associated with an additional 5.34 kg weight reduction versus liraglutide (p<0.0001), while semaglutide showed no significant difference. Higher baseline weight also predicted modest additional weight loss in T2D individuals (β2=-0.1159, p=-2.0177). Regarding glycemic control in T2D, tirzepatide was associated with an HbA1c reduction of approximately 0.8% compared to liraglutide (p<0.0001), while semaglutide demonstrated a non-significant trend. Baseline HbA1c and follow-up duration were not significant moderators for glycemic control.
CONCLUSIONS: The analysis showed tirzepatide was associated with significant reductions in both body weight and HbA1c. Baseline body weight was identified as a key predictor for the magnitude of weight loss in both non-diabetic and T2D populations. The MLMA methodology provided a mathematically conservative and reliable estimate for these complex, multi-arm trial data.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO169
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)