Impact of Semaglutide, Liraglutide and Tirzepatide on Cardiometabolic Outcomes: A Comparative Narrative Review.

Hiba Bawadi, Haya Abuhijleh, Mamon Nofal, Zain Z Zakaria, Maha Al-Asmakh

Journal: Endocrinology, diabetes & metabolism 2026;9(5):e70338

PMID: 42747132

Abstract

BACKGROUND

Cardiometabolic disorders such as type 2 diabetes mellitus (T2DM), obesity and cardiovascular disease (CVD) remain major global health challenges. Incretin-based therapies, including the GLP-1 receptor agonists semaglutide and liraglutide, and the dual GIP/GLP-1 receptor agonist tirzepatide, are increasingly used to address hyperglycaemia and obesity, and have been evaluated for both cardiometabolic risk markers and selected cardiovascular and renal outcomes.

OBJECTIVE

This review summarizes and contrasts the pharmacology of semaglutide, liraglutide and tirzepatide, distinguishing between surrogate cardiometabolic risk markers (e.g., glycaemic control, body weight and lipid parameters) and confirmed clinical outcomes, including major adverse cardiovascular events (MACE) and renal endpoints.

METHODS

Recent data were synthesized from pivotal randomized clinical trial programs, SUSTAIN and PIONEER (semaglutide), LEADER (liraglutide) and SURPASS and SURMOUNT (tirzepatide), as well as meta-analyses, post hoc analyses and observational studies addressing mechanistic and long-term cardiometabolic outcomes.

RESULTS

All three agents improved HbA1c, weight and cardiometabolic outcomes, with tirzepatide generally showing greater reductions across clinical trials. Semaglutide and liraglutide consistently improved BMI, lipid profile and cardiovascular risk, while tirzepatide shows promise pending CVOT data. Renal outcomes were favourable across the class, though results varied by baseline characteristics and trial design.

CONCLUSION

Semaglutide, liraglutide and tirzepatide are key therapies for type 2 diabetes and cardiometabolic disease. Tirzepatide's dual activity may enhance metabolic and lipid outcomes, while semaglutide and liraglutide have strong evidence for cardiovascular and renal safety. However, comparisons are based on indirect evidence and should be interpreted cautiously.

Address: Department of Human Nutrition, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar.; Clinical Affairs Department, QU-HEALTH, Qatar University, Doha, Qatar.; Department of Human Nutrition, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar.; Department of Biomedical Sciences, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar.; Nottingham University Hospitals NHS Trust, Nottingham, UK.; Clinical Affairs Department, QU-HEALTH, Qatar University, Doha, Qatar.; Department of Biomedical Sciences, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar.; Biomedical Research Center, QU-HEALTH, Qatar University, Doha, Qatar.

DOI: 10.1002/edm2.70338

MeSH Terms: Humans, Tirzepatide, Semaglutide, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Liraglutide, Cardiovascular Diseases, Hypoglycemic Agents, Obesity, Glucagon-Like Peptide-1 Receptor Agonists