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

Q: What is the clinical evidence from this study?

Study design: Review. Population: Type 2 diabetes mellitus, obesity, and related cardiometabolic comorbidities. Intervention: Tirzepatide vs. Placebo or active comparators (e.g., semaglutide, insulin).

Q: What does this research mean for the field?

Tirzepatide reduces glycated hemoglobin by up to 2.5% and body weight by more than 20% across clinical trials while improving cardiovascular risk factors and outcomes in HFpEF and OSA. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Mrudula Thiriveedi; Francis Sto. Domingo; Hannah Yates; Sujatha Baddam; Rafik El Beblawy; Bala Nimmana; Siddharth Patel

doi:10.1097/ms9.0000000000004055

November 12, 2025Annals of Medicine and SurgeryOpen Access

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

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Key result

Tirzepatide cuts body weight by over ~20% while significantly improving HbA1c and cardiometabolic risk factors.

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Why the study?

Tirzepatide represents a new class of dual GLP-1 and GIP receptor agonist incretin-based therapy for type 2 diabetes mellitus, obesity, and related comorbidities.

Does tirzepatide improve glycemic control, promote weight loss, and provide cardioprotection in patients with type 2 diabetes mellitus, obesity, and related comorbidities?

Structured PICO

Does tirzepatide improve glycemic control, promote weight loss, and provide cardioprotection in patients with type 2 diabetes mellitus, obesity, and related comorbidities?

P

Population

A narrative review synthesizing evidence from multiple clinical trials (SURPASS, SURMOUNT, SUMMIT) evaluating tirzepatide in patients with type 2 diabetes, obesity, heart failure with preserved ejection fraction, and obstructive sleep apnea.

I

Intervention

Tirzepatide (5 mg, 10 mg, or 15 mg once weekly)

C

Comparator

Placebo, semaglutide (1 mg), insulin degludec, or insulin glargine

O

Outcome

Glycemic control (HbA1c reduction), percent weight loss, cardiovascular death or heart failure hospitalization, and apnea-hypopnea index (AHI) reduction

Tirzepatide is a dual GIP/GLP-1 receptor agonist that delivers unprecedented weight loss and robust glycemic control, with emerging evidence for significant clinical benefits in HFpEF and OSA, expanding the role of incretin therapies in multi-system cardiometabolic disease management.

Limitations

Long-term durability of glycemic and weight benefits remains uncertain due to 40-52 week trial durations.
Cardiovascular outcomes were not designated as primary endpoints in earlier trials, limiting conclusions on event reduction.
Patients with severe renal or hepatic dysfunction were often excluded from trials.
Weight regain occurs upon cessation of the medication, requiring chronic or maintenance dosing.
Long-term safety data beyond 2 years are limited, and pediatric populations have been excluded from all major clinical trials.
Short trial durations (mostly 40-52 weeks)
Cardiovascular outcomes were not primary endpoints in earlier trials
Exclusion of patients with severe renal or hepatic dysfunction
Weight regain upon cessation of therapy
Limited long-term safety data beyond 2 years
Exclusion of pediatric populations

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Implication

Supports expanded cardiometabolic use of tirzepatide; leaves open confirmation of hard cardiovascular outcomes in dedicated trials.

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.

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Cite This Study

Thiriveedi et al. (2025) conducted a review in Type 2 diabetes mellitus, obesity, and related cardiometabolic comorbidities. Tirzepatide vs. Placebo or active comparators (e.g., semaglutide, insulin) was evaluated. Tirzepatide significantly reduced HbA1c by up to 2.5% and body weight by over 20% across multiple trials, while also improving cardiometabolic risk factors in patients with type 2 diabetes and obesity.

synapsesocial.com/papers/6a145188c4c5e9e51862cc09 https://doi.org/10.1097/ms9.0000000000004055

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

Figures

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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

Figures

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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