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Type 2 diabetes mellitus (T2DM) is one of the leading causes of morbidity and mortality. Peptide-based multi-targeting agonists represent a new paradigm in metabolic pharmacology as they manifest multiplexed pharmacological actions over mono-agonists. Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R) agonist that has been recently approved by the FDA. This review aims to summarize the available evidence on the discovery, pharmacology, pharmacokinetic, pharmacodynamic, efficacy, and safety of tirzepatide in the pharmacotherapy of T2DM. We searched PubMed, Embase, and International Pharmaceutical Abstracts to identify relevant papers on tirzepatide use in T2DM. Clinical trial registries were also searched. Tirzepatide improves glycemic control compared to baseline, placebo, and active comparators. It is also associated with weight reduction and an improvement in some, but not all, dyslipidemia, cardiovascular risk, and nonalcoholic steatohepatitis (NASH) biomarkers. Tirzepatide has a favorable safety profile with a low risk of hypoglycemia; however, adverse events such as gastrointestinal reactions were frequently reported and sometimes even led to therapy discontinuation. Future research should focus on investigating the role of tirzepatide in obesity, NASH, and cardio-renal benefits. Real-world observational studies are also needed to assess rare and long-term adverse events.

Profile of tirzepatide in the management of type 2 diabetes mellitus: design, development, and place in therapy