Tirzepatide 5, 10, and 15 mg resulted in statistically significant greater reductions in and body weight compared to all GLP-1 RA comparators and placebo.
Tirzepatide demonstrated greater changes in glycated haemoglobin (HbA1c) levels and body weight at the primary endpoint compared to GLP-1 receptor agonists and placebo.
Patients receiving tirzepatide had a statistically significant higher likelihood of experiencing nausea compared to those on placebo or exenatide 2 mg.
No significant differences were observed in treatment discontinuation due to adverse events when comparing tirzepatide with GLP-1 RA comparators, except for tirzepatide 10 and 15 mg versus placebo.
The overall safety profile of tirzepatide was similar to that of GLP-1 receptor agonists.
Simplified
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 (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 () 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.
Key numbers
14.8×
Increase in likelihood of achieving < 7.0%
Likelihood of achieving < 7.0% with vs. lixisenatide.
0.86%
Reduction in
Change from baseline in with .
6.1
Proportion of patients experiencing nausea
Proportion experiencing nausea with 15 mg vs. .
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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.
