Dose-Response and Clinical Equivalence of Semaglutide and Tirzepatide for Weight Loss in Type 2 Diabetes: A Model-Based Analysis.

IF 4.2 3区医学 Q2 Medicine

Diabetes Therapy Pub Date : 2026-07-01 Epub Date: 2026-06-07 DOI:10.1007/s13300-026-01886-0

Carlos E Builes-Montaño, Andres F Suarez-Rodriguez, Maria A Alzate-Vinasco

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引用次数: 0

Abstract

Introduction: Semaglutide and tirzepatide are highly effective incretin-based therapies for weight reduction in individuals with type 2 diabetes (T2DM). However, direct comparisons across the full range of clinically relevant doses in T2DM are limited. This study aimed to evaluate dose-response relationships and clinical equivalence between semaglutide and tirzepatide using a model-based approach.

Methods: Arm-level data from phase III randomized controlled trials of semaglutide (SUSTAIN, STEP) and tirzepatide (SURPASS, SURMOUNT-2) in T2DM were analyzed. Dose-response relationships for percent weight change were modeled using generalized additive models and Bayesian hierarchical spline models. Posterior probabilities of clinical equivalence were estimated across prespecified dose pairs using an equivalence margin of ± 2 percentage points. Model-based intensification scenarios were evaluated to estimate incremental benefit associated with treatment switching or dose escalation.

Results: A total of 48 treatment arms (n = 16,524 participants) were included. Both agents demonstrated nonlinear dose-response relationships, with attenuation of incremental effects at higher doses. High probabilities of equivalence were observed for semaglutide 2.4 mg versus tirzepatide 10 mg (99.4%) and semaglutide 7.2 mg versus tirzepatide 15 mg (94.8%). Lower doses of semaglutide were not equivalent to higher doses of tirzepatide. In intensification scenarios, both switching and dose escalation strategies improved weight loss, although the probability of achieving ≥ 2 additional percentage points varied across regimens.

Conclusion: Semaglutide and tirzepatide demonstrate comparable weight-loss efficacy at specific dose combinations, with equivalence driven by dose rather than drug identity. Model-based analyses provide a quantitative framework to support individualized treatment decisions when direct comparative evidence is unavailable.

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西马鲁肽和替西帕肽对2型糖尿病减肥的剂量反应和临床等效性：基于模型的分析。

介绍：西马鲁肽和替西肽是2型糖尿病（T2DM）患者高效的以肠促胰岛素为基础的减肥疗法。然而，T2DM临床相关剂量的全范围直接比较是有限的。本研究旨在使用基于模型的方法评估西马鲁肽和替西帕肽的剂量-反应关系和临床等效性。方法：分析西马鲁肽（SUSTAIN， STEP）和替西帕肽（exceed, SURMOUNT-2）治疗T2DM的III期随机对照试验的臂水平数据。采用广义加性模型和贝叶斯层次样条模型对百分比体重变化的剂量-响应关系进行了建模。临床等效的后验概率在预先指定的剂量对中估计，等效裕度为±2个百分点。评估了基于模型的强化方案，以估计与治疗转换或剂量增加相关的增量效益。结果：共纳入48个治疗组（n = 16,524名受试者）。两种药物都表现出非线性的剂量-反应关系，随着剂量的增加而衰减。塞马鲁肽2.4 mg与替西帕肽10 mg（99.4%）、塞马鲁肽7.2 mg与替西帕肽15 mg（94.8%）的等效概率很高。低剂量的西马鲁肽并不等同于高剂量的替西帕肽。在强化方案中，转换策略和剂量递增策略都改善了体重减轻，尽管在不同方案中实现≥2个额外百分点的可能性有所不同。结论：西马鲁肽和替西帕肽在特定剂量组合下具有相当的减肥效果，其等效性是由剂量驱动的，而不是由药物同一性驱动的。当没有直接的比较证据时，基于模型的分析提供了一个定量框架来支持个性化的治疗决策。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes Therapy Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

6.90

自引率

7.90%

发文量

130

审稿时长

6 weeks

期刊介绍： Diabetes Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all areas of diabetes. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Diabetes Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.