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

Sep 29, 2026

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Tirzepatide, a dual GLP-1 and GIP receptor agonist, is reviewed as an incretin-based therapy for type 2 diabetes mellitus, obesity, and related cardiometabolic comorbidities. Evidence synthesized from the SURPASS, SURMOUNT, and SUMMIT clinical programs shows reductions in HbA1c up to 2.5% and body weight by over 20%, alongside improvements in cardiovascular risk markers such as blood pressure, lipids, and inflammation. The review also reports benefits in HFpEF and obstructive sleep apnea, while noting safety monitoring needs for gastrointestinal effects, gallbladder events, and thyroid cancer signals.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Role in type 2 diabetes and obesity

Rationale for cardiometabolic risk reduction

Mechanism and clinical evidence

Dual incretin (GLP-1/GIP) action

Summary of outcomes from clinical trial programs

Safety considerations and ongoing questions

Adverse events to monitor

Off-label, weight regain, and access challenges

Future outcome trials

Review A narrative review on tirzepatide’s therapeutic potential in glycemic control and cardioprotection Mrudula Thiriveedi, MDa ,*, Francis Sto. Domingo, DOb , Hannah Yates, DOb , Sujatha Baddam, MDc , Rafik El Beblawy, MDa , Bala Nimmana, MDc , Siddharth Patel, MBBS, MPHa Abstract 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. Keywords: cardioprotection, dual incretin agonist, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) Introduction Metabolic diseases such as type 2 diabetes mellitus (T2DM) and obesity are closely linked to cardiovascular disease (CVD), leading to a global epidemic of morbidity and mortality[1,2] . Despite advances in treatment, many patients still struggle to achieve adequate glycemic control, weight loss, and risk factor reduction[3] . Metabolic and cardiovascular complications (e.g., atherosclerosis and heart failure) remain the leading causes of death worldwide. There is an urgent need for therapies that address multiple aspects of this cardiometabolic syndrome, such as improving blood glucose levels, reducing body weight, and mitigating cardiovascular risk[4,5] . In recent years, incretin-based therapies (such as glucagonlike peptide-1 (GLP-1) receptor agonists) have transformed the aDepartment of Internal Medicine, Decatur Morgan Hospital, Decatur, Alabama, USA, bDepartment of Medicine, Alabama College of Osteopathic Medicine, Dothan, Alabama, USA and cDepartment of Internal Medicine, Huntsville Hospital, Huntsville, Alabama, USA Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: Department of Internal Medicine, Decatur Morgan Hospital, 1201 7th Street SE, Decatur 35601, Alabama, USA. [Tel.: 651-703-9007. E-mail: drmrudula.giridhar@gmail.com](Tel.: 651-703-9007. E-mail: drmrudula.giridhar@gmail.com) (M. Thiriveedi). Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Annals of Medicine & Surgery (2026) 88:371–380 Received 30 June 2025; Accepted 29 September 2025 Published online 13 November 2025 [http://dx.doi.org/10.1097/MS9.0000000000004055](http://dx.doi.org/10.1097/MS9.0000000000004055) HIGHLIGHTS ● Tirzepatide, a dual GIP and GLP-1 receptor agonist, shows unprecedented glycemic and weight-loss benefits in patients with type 2 diabetes and obesity. ● FDA approvals now include treatment for type 2 diabetes, chronic weight

FAQs

What is tirzepatide and how does it work?

Tirzepatide is a first-in-class dual incretin agonist that activates both GLP-1 and GIP receptors. This dual mechanism targets glucose control, weight reduction, and cardiometabolic risk pathways.

What benefits does tirzepatide show for glycemic control and weight?

Across the SURPASS, SURMOUNT, and SUMMIT trial programs, tirzepatide reduced HbA1c by up to 2.5% and body weight by more than 20%. It also improved cardiovascular risk factors.

What safety issues require monitoring?

The review states that the safety profile aligns with GLP-1 receptor agonists but emphasizes monitoring for gastrointestinal side effects, gallbladder events, and thyroid cancer signals.

Sep 29, 2026

Uploaded by OmBimo