# Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction

Review · Michael Albrecht Nauck, David A. D’Alessio

- Archive id: doi:10.1186/s12933-022-01604-7
- Published: 2022-09-01
- Venue: Cardiovascular Diabetology
- DOI: https://doi.org/10.1186/s12933-022-01604-7
- PMID: 36050763
- PMCID: PMC9438179
- Citations: 405
- Source URL: https://doi.org/10.1186/s12933-022-01604-7
- PDF: https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-022-01604-7
- Provenance: openalex+europepmc

## Abstract

and body weight than the selective GLP-1 RA semaglutide (1.0 mg per week), and titrated basal insulin. Adverse events related to tirzepatide were similar to what has been reported for selective GLP-1RA, mainly nausea, vomiting, diarrhoea, and constipation, that were more common at higher doses. Cardiovascular events have been adjudicated across the whole study program, and MACE-4 (nonfatal myocardial infarction, non-fatal stroke, cardiovascular death and hospital admission for angina) events tended to be reduced over up to a 2 year-period, albeit with low numbers of events. For none of the cardiovascular events analysed (MACE-4, or its components) was a hazard ratio \> 1.0 vs. pooled comparators found in a meta-analysis covering the whole clinical trial program, and the upper bounds of the confidence intervals for MACE were \< 1.3, fulfilling conventional definitions of cardiovascular safety. Tirzepatide was found to improve insulin sensitivity and insulin secretory responses to a greater extent than semaglutide, and this was associated with lower prandial insulin and glucagon concentrations. Both drugs caused similar reductions in appetite, although tirzepatide caused greater weight loss. While the clinical effects of tirzepatide have been very encouraging, important questions remain as to the mechanism of action. While GIP reduces food intake and body weight in rodents, these effects have not been demonstrated in humans. Moreover, it remains to be shown that GIPR agonism can improve insulin secretion in type 2 diabetic patients who have been noted in previous studies to be unresponsive to GIP. Certainly, the apparent advantage of tirzepatide, a dual incretin agonist, over GLP-1RA will spark renewed interest in the therapeutic potential of GIP in type 2 diabetes, obesity and related co-morbidities.

_Abstract reproduced under CC-BY (publisher license, via OpenAlex)._

Topics: [GLP-1 & Incretin Therapies](https://space-kitty.com/topics/glp1-metabolic)

Cited in dossiers:
- [GLP-1 & Incretin Therapies: State of the Field (October 2026)](https://space-kitty.com/dossiers/glp1-metabolic)

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