Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun;16(6):1279-1311.
doi: 10.1007/s13300-025-01728-5. Epub 2025 Apr 11.

Efficacy and Safety of Tirzepatide Compared with GLP-1 RAs in Patients with Type 2 Diabetes Treated with Basal Insulin: A Network Meta-analysis

Beatrice Osumili  1 , Hélène Sapin  2 , Zhengyu Yang  3 , Kari Ranta  4 , Jim S Paik  5 , Matthias Blüher  6
Affiliations

Efficacy and Safety of Tirzepatide Compared with GLP-1 RAs in Patients with Type 2 Diabetes Treated with Basal Insulin: A Network Meta-analysis

Beatrice Osumili et al. Diabetes Ther. 2025 Jun.

Abstract

Introduction: The relative efficacy and safety of tirzepatide was compared with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM) treated with basal insulin using a network meta-analysis (NMA).

Methods: A systematic literature review was performed to identify randomized controlled trials of GLP-1 RAs in patients with T2DM treated with insulin and an antihyperglycaemic drug. For the NMA, studies included trials with 100% of patients treated with basal insulin background therapy with a titration scheme comparable to the SURPASS-5 trial. The following data were extracted for efficacy and safety assessment at the primary endpoint of each study: changes from baseline in glycated haemoglobin (HbA1c) and body weight and the incidence of nausea, vomiting or diarrhoea, hypoglycaemia, and patients discontinuing treatment because of adverse events. In this study, a comparative analysis of tirzepatide was performed with the GLP-1 RAs dulaglutide, exenatide, and lixisenatide in addition to placebo.

Results: A total of six studies were included across the analyses. Tirzepatide 5, 10, and 15 mg showed statistically significant, greater reductions in HbA1c and body weight at the primary endpoint versus all GLP-1 RA comparators and placebo. Tirzepatide 5, 10, and 15 mg showed a statistically significant, higher likelihood of experiencing nausea compared with those who received placebo or exenatide 2 mg; no statistically significant differences were observed when compared with all other GLP-1 RA comparators. No statistically significant differences were observed in the proportions of patients who discontinued treatment because of adverse events when tirzepatide 5, 10, and 15 mg were compared with GLP-1 RA comparators, apart from tirzepatide 10 and 15 mg versus placebo.

Conclusion: Tirzepatide demonstrated statistically significantly greater reductions in HbA1c and body weight when compared with selected GLP-1 RAs and placebo in patients with T2DM treated with basal insulin. Overall, the safety profile of tirzepatide was similar to that of GLP-1RAs.

Keywords: Basal insulin; GLP-1 receptor agonists; Glycaemic control; Network meta-analysis; Tirzepatide; Type 2 diabetes mellitus.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of Interest: Beatrice Osumili, Kari Ranta, Hélène Sapin, and Jim S. Paik are employees and minor shareholders of Eli Lilly and Company. Zhengyu Yang was an employee and shareholder of Eli Lilly and Company during the development of the NMA and the manuscript and is currently an employee of Amylyx Pharmaceuticals. Matthias Blüher received honoraria as a consultant and speaker for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly and Company, Novartis, Novo Nordisk, Pfizer, and Sanofi. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of the SLR and NMA. The rationale for including and excluding trials is detailed in Sect. 2 of the Supplementary Material. NMA network meta-analysis, OADs oral antihyperglycaemic drugs, PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses, SLR systematic literature review, wk week(s)
Fig. 2
Fig. 2
Evidence network for 6 studies and 8 treatments (nodes) included in the network meta-analysis. The thickness of the lines indicates the number of studies comparing between the interventions, and the radius of the circle shows the number of studies within a given treatment arm. Outcomes included change from baseline in HbA1c; proportion of patients reaching target HbA1c < 7.0%; change from baseline in weight (kg); proportion of patients experiencing nausea, vomiting, and diarrhoea; proportion of patients with ≥ 1 episode of hypoglycaemia with blood glucose < 54 mg/dL (with or without severe hypoglycaemia); and proportion of patients with treatment discontinuation. BID twice daily, HbA1c glycated haemoglobin, QW once weekly
Fig. 3
Fig. 3
Forest plots of change in a HbA1c, b likelihood of patients reaching HbA1c < 7.0%, and c likelihood of patients reaching HbA1c ≤ 6.5% from baseline to week 40 (TZP) and week 26 ± 4 weeks (comparators). BID twice daily, CrI credible interval, HbA1c glycated haemoglobin, QW once weekly, TZP tirzepatide
Fig. 4
Fig. 4
Forest plots of change in body weight from baseline to week 40 (TZP) and week 26 ± 4 weeks (comparators). BID twice daily, CrI credible interval, QW once weekly, TZP tirzepatide
Fig. 5
Fig. 5
Forest plots of likelihood of patients experiencing a nausea, b vomiting, and c diarrhoea from baseline to week 40 (TZP) and week 26 ± 4 weeks (comparators). BID twice daily, CrI credible interval, QW once weekly, TZP tirzepatide
Fig. 6
Fig. 6
Forest plots of the likelihood of patients with ≥ 1 episode of hypoglycaemia with BG < 54 mg/dL (with or without severe hypoglycaemia) from baseline to week 40 (TZP) and week 26 ± 4 weeks (comparators). BG blood glucose, BID twice daily, CrI credible interval, QW once weekly, TZP tirzepatide
Fig. 7
Fig. 7
Forest plots of the likelihood of patients with treatment discontinuation due to AEs from baseline to week 40 (TZP) and week 26 ± 4 weeks (comparators). AE adverse event, BID twice daily, CrI credible interval, QW once weekly, TZP tirzepatide
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Nasykhova YA, Tonyan ZN, Mikhailova AA, Danilova MM, Glotov AS. Pharmacogenetics of type 2 diabetes-progress and prospects. Int J Mol Sci. 2020;21(18):6842. - PMC - PubMed
    1. Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al KJ. Epidemiology of type 2 diabetes–global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10(1):107–11. - PMC - PubMed
    1. Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther. 2008;88(11):1322–35. - PMC - PubMed
    1. Seuring T, Archangelidi O, Suhrcke M. The economic costs of type 2 diabetes: a global systematic review. Pharmacoeconomics. 2015;33(8):811–31. - PMC - PubMed
    1. Landgraf R, Aberle J, Birkenfeld AL, et al. Therapy of type 2 diabetes. Exp Clin Endocrinol Diabetes. 2019;127(Suppl 1):S73–92. - PubMed

LinkOut - more resources