Effects of Tirzepatide on Pancreatic β-Cell Function in Adults With Type 2 Diabetes Mellitus: A Systematic Review.
9 affiliations
- 1Ophthalmology, University of Khartoum, Khartoum, SDN.
- 2Endocrinology, Sligo University Hospital, Sligo, IRL.
- 3Internal Medicine, University Hospital Kerry, Tralee, IRL.
- 4Endocrinology, Dr. Sulaiman Al Habib Hospital, Riyadh, SAU.
- 5General Medicine, Ahfad University for Women, Khartoum, SDN.
- 6General Medicine, Bon Secours Hospital Limerick, Limerick, IRL.
- 7Internal Medicine, Bupa Care Connect, Jeddah, SAU.
- 8General Medicine, Nizwa Hospital, Nizwa, OMN.
- 9Quality Improvement and Patient Safety, Najran Armed Forces Hospital, Ministry of Defense Health Services, Najran, SAU.
Abstract
Type 2 diabetes mellitus (T2DM) is driven by progressive pancreatic β-cell failure, and few glucose-lowering agents demonstrably modify this defect. This systematic review assessed whether tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, improves β-cell function in adults with T2DM. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, PubMed, Web of Science, Scopus and Embase were searched from inception to July 29, 2026, with citation searching. Eligible reports were original peer-reviewed primary human studies reporting a quantitative measure of β-cell function in adults receiving subcutaneous tirzepatide; preclinical and non-original reports were excluded. Risk of bias was appraised with risk of bias 2 (RoB 2) tool and The Risk Of Bias In Non-randomized Studies of Interventions, Version 2 (ROBINS-I). Heterogeneity of outcome metrics precluded meta-analysis, so findings were synthesised narratively. Eight reports representing six distinct populations and 3,442 unique participants were included. Tirzepatide 5-15 mg weekly raised the Homeostasis Model Assessment 2 of Beta-cell Function (HOMA2-B) by 77% to 163% from baseline, exceeding placebo, dulaglutide and semaglutide 1 mg; fasting intact proinsulin and the intact proinsulin/C-peptide ratio fell by up to 55% and 49%; and the clamp disposition index rose approximately six-fold. Fasting insulin and C-peptide fell in parallel, indicating reduced secretory demand. Risk of bias was low in four reports, of some concern in one, high in two and serious in one. Tirzepatide improves β-cell function indices beyond selective GLP-1 receptor agonism, but the evidence rests largely on post hoc, industry-funded analyses and no study examined function after drug withdrawal. This review was unfunded and unregistered.
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BibTeX
@article{mahmoud2026effects,
title = {{Effects of Tirzepatide on Pancreatic β-Cell Function in Adults With Type 2 Diabetes Mellitus: A Systematic Review.}},
author = {Rasha Mahmoud and Ahmed Abdalla Zarrouq Yousif and Alaa Fathelrahman Mokhtar Osman and Eltayeb Osman Elfaki Omer and Ayaa Ismail Ahmed Talaat and Omima Mohamed and Shereen Alnagi Mohammed Akasha and Emad Salah Fathy Saleh and Hanady Me M Osman},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.116733},
url = {https://europepmc.org/article/MED/42923463},
note = {CC BY},
}
RIS
TY - JOUR
TI - Effects of Tirzepatide on Pancreatic β-Cell Function in Adults With Type 2 Diabetes Mellitus: A Systematic Review.
AU - Rasha Mahmoud
AU - Ahmed Abdalla Zarrouq Yousif
AU - Alaa Fathelrahman Mokhtar Osman
AU - Eltayeb Osman Elfaki Omer
AU - Ayaa Ismail Ahmed Talaat
AU - Omima Mohamed
AU - Shereen Alnagi Mohammed Akasha
AU - Emad Salah Fathy Saleh
AU - Hanady Me M Osman
PY - 2026
DA - 2026/09/22
JO - Cureus
DO - 10.7759/cureus.116733
UR - https://europepmc.org/article/MED/42923463
AB - Type 2 diabetes mellitus (T2DM) is driven by progressive pancreatic β-cell failure, and few glucose-lowering agents demonstrably modify this defect. This systematic review assessed whether tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, improves β-cell function in adults with T2DM. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, PubMed, Web of Science, Scopus and Embase were searched from inception to July 29, 2026, with citation searching. Eligible reports were original peer-reviewed primary human studies reporting a quantitative measure of β-cell function in adults receiving subcutaneous tirzepatide; preclinical and non-original reports were excluded. Risk of bias was appraised with risk of bias 2 (RoB 2) tool and The Risk Of Bias In Non-randomized Studies of Interventions, Version 2 (ROBINS-I). Heterogeneity of outcome metrics precluded meta-analysis, so findings were synthesised narratively. Eight reports representing six distinct populations and 3,442 unique participants were included. Tirzepatide 5-15 mg weekly raised the Homeostasis Model Assessment 2 of Beta-cell Function (HOMA2-B) by 77% to 163% from baseline, exceeding placebo, dulaglutide and semaglutide 1 mg; fasting intact proinsulin and the intact proinsulin/C-peptide ratio fell by up to 55% and 49%; and the clamp disposition index rose approximately six-fold. Fasting insulin and C-peptide fell in parallel, indicating reduced secretory demand. Risk of bias was low in four reports, of some concern in one, high in two and serious in one. Tirzepatide improves β-cell function indices beyond selective GLP-1 receptor agonism, but the evidence rests largely on post hoc, industry-funded analyses and no study examined function after drug withdrawal. This review was unfunded and unregistered.
SN - 2168-8184
ER -