International Journal of Research in Pharmacy and Allied Science

ISSN: 2583-6544   |  Issues per year: Monthly  |   Indexed In: Google Scholar, CORE, ScienceOpen, Researchgate

ISSN:2583-6544

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Dual Incretin Agonism in Type 2 Diabetes and Obesity: Systematic Review of Tirzepatide Mechanisms and Clinical Outcomes

Author(s): Jefferson Lorençoni de Morais1*1, Lanna Araújo Gomes22, Larissa Neres Barbosa3

Email(s): 1jefferson.morais@unialfa.com.br

Address:

    1. Polytechnic School of the Alves Faria University Center - UNIALFA. 2. Institute of Pharmaceutical Sciences. University Center of Goiás – UNIGOIÁS

Published In:   Volume - 5,      Issue - 3,     Year - 2026

DOI: https://doi.org/10.71431/IJRPAS.2026.5309  

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ABSTRACT:
Type 2 diabetes mellitus (T2DM) and obesity are complex metabolic disorders driven by insulin resistance, pancreatic β-cell dysfunction, hormonal dysregulation, and vascular impairment. This systematic review, conducted in accordance with PRISMA 2020 guidelines, synthesized evidence published between 2006 and 2025 regarding the pathophysiological mechanisms of T2DM and obesity, the role of incretin system dysfunction, and the clinical implications of tirzepatide—a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. A comprehensive literature search across PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Embase identified 180 records, of which 20 studies met the inclusion criteria and were qualitatively analyzed. Evidence demonstrates that T2DM progression involves the renin–angiotensin system, impaired incretin signaling, and progressive β-cell exhaustion. Tirzepatide therapy was consistently associated with superior reductions in glycated hemoglobin (1.8–2.4%), significant and sustained weight loss (up to 20% of baseline body weight), improved insulin sensitivity, and favorable cardiometabolic effects compared with selective GLP-1 receptor agonists. The safety profile was characterized by mild-to-moderate gastrointestinal adverse events and low hypoglycemia risk. These findings underscore the role of dual incretin receptor agonism as a mechanistically innovative therapeutic strategy for T2DM and obesity, with direct implications for pharmacy practice in therapeutic decision-making and patient counseling.

Keywords:

Cite this article:
Jefferson Lorençoni de Morais, Lanna Araújo Gomes, Larissa Neres Barbosa. Dual Incretin Agonism in Type 2 Diabetes and Obesity: Systematic Review of Tirzepatide Mechanisms and Clinical Outcomes. IJRPAS, March 2026; 5(3): 125-137.DOI: https://doi.org/https://doi.org/10.71431/IJRPAS.2026.5309


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