This review compares and GLP-1/GIP dual agonists across metabolic, cardiovascular, neuropsychiatric, perioperative, and multi-receptor drug-development uses.
Evidence
The evidence is a narrative review synthesizing pharmacologic mechanisms, therapeutic efficacy, and safety profiles for GLP-1RAs, tirzepatide-like dual agonists, and newer dual or triple agonists.
Caveat
Because it is a review rather than a new trial, its clinical conclusions depend on the scope and quality of the underlying studies across heterogeneous indications.
Simplified
This review provides a comprehensive examination of the clinical pharmacological mechanisms and broad therapeutic applications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual receptor agonists targeting both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. GLP-1RAs exert their effects by stimulating insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite through the activation of the GLP-1 receptor. These agents have demonstrated significant efficacy in the management of type 2 diabetes mellitus (T2DM) and obesity. Moreover, emerging evidence suggests that GLP-1RAs may confer cardiovascular protection, neuroprotective benefits, and positive effects on mental health. , such as tirzepatide, simultaneously activate both receptors, thereby potentiating glycemic control, promoting weight loss, and ameliorating metabolic dysfunction. This review also addresses recent advances in the development of other dual and triple receptor agonists. Distinct from prior reviews that predominantly focus on a single drug class or limited clinical indications, this article systematically contrasts the mechanistic pathways, therapeutic efficacy, and safety profiles of GLP-1RAs versus GLP-1/GIP dual receptor agonists. Notably, it integrates the most current evidence pertaining to novel domains, such as perioperative management, neuropsychiatric outcomes, and the innovation of multi-receptor agonists. This synthesis offers a timely and practical resource to inform clinical precision medicine and to guide future investigative efforts.
Key numbers
17.4%
Weight Loss
Mean body weight reduction with oral semaglutide in a phase III trial.
0.8%
Reduction
Average reduction with compared to baseline.
28%
Cardiovascular Event Reduction
Potential risk reduction of major adverse cardiovascular events with compared to placebo.
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