A narrative review on tirzepatide’s therapeutic potential in glycemic control and cardioprotection

Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, represents a new class of incretin-based therapy for type 2 diabetes mellitus (T2DM), obesity, and related comorbidities. This narrative review synthesizes evidence from the SURPASS, SURMOUNT, and SUMMIT clinical trial programs. Across studies, tirzepatide reduced glycated hemoglobin (HbA1c) by up to 2.5% and body weight by more than 20%. It also improved cardiovascular risk factors (blood pressure, lipids, inflammation) and has demonstrated benefits in patients with heart failure with preserved ejection fraction (HFpEF) and obstructive sleep apnea (OSA), with reductions in the apnea-hypopnea index (AHI) and heart failure hospitalizations. Its safety profile is consistent with that of GLP-1 receptor agonists (GLP-1 RAs), although gastrointestinal side effects, gallbladder events, and thyroid cancer signals warrant monitoring. Ethical concerns related to off-label use, weight regain after discontinuation, and barriers to real-world access remain active issues. Ongoing outcome trials and real-world data will clarify its long-term role and potential integration into future clinical guidelines.