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Review
. 2025 May 30;15(6):796.
doi: 10.3390/biom15060796.

Retatrutide-A Game Changer in Obesity Pharmacotherapy

Vasiliki Katsi  1 , Georgios Koutsopoulos  1 , Christos Fragoulis  1 , Kyriakos Dimitriadis  1 , Konstantinos Tsioufis  1
Affiliations
Review

Retatrutide-A Game Changer in Obesity Pharmacotherapy

Vasiliki Katsi et al. Biomolecules. .

Abstract

Obesity and type 2 diabetes mellitus (T2DM) are global health crises with significant morbidity and mortality. Retatrutide, a novel triple receptor agonist targeting glucagon-like peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and glucagon receptors, represents a groundbreaking advancement in obesity and T2DM pharmacotherapy. This review synthesizes findings from preclinical and clinical studies, highlighting retatrutide's mechanisms, efficacy, and safety profile. Retatrutide's unique molecular structure enables potent activation of GLP-1, GIP, and glucagon receptors, leading to significant weight reduction, improved glycemic control, and favorable metabolic outcomes. Animal studies demonstrate retatrutide's ability to delay gastric emptying, reduce food intake, and promote weight loss, with superior efficacy compared to other incretin-based therapies. Phase I and II clinical trials corroborate these findings, showing dose-dependent weight loss, reductions in Glycated Hemoglobin (HbA1c) levels, and improvements in liver steatosis and diabetic kidney disease. Common adverse effects are primarily gastrointestinal and dose-related. Ongoing Phase III trials, such as the TRIUMPH studies, aim to further evaluate retatrutide's long-term safety and efficacy in diverse patient populations. While retatrutide shows immense promise, considerations regarding cost and the quality of weight loss beyond BMI reduction warrant further investigation. Retatrutide heralds a new era in obesity and T2DM treatment, offering hope for improved patient outcomes.

Keywords: incretins; obesity; retatrutide; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Retatrutide’s mechanisms of action.
Figure 2
Figure 2
The present and future of Retatrutide.
See this image and copyright information in PMC

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