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
Clinical Trial
. 2025 Sep 1;48(9):1622-1627.
doi: 10.2337/dc25-0763.

Tirzepatide Treatment and Associated Changes in β-Cell Function and Insulin Sensitivity in People With Obesity or Overweight With Prediabetes or Normoglycemia: A Post Hoc Analysis From the SURMOUNT-1 Trial

Andrea Mari  1 , Adam Stefanski  2 , Daniel H van Raalte  3 , Xiaosu Ma  2 , Elizabeth S LaBell  2 , Ludi Fan  2 , Clare J Lee  2 , Melissa K Thomas  2 , Mathijs C Bunck  2 , Ele Ferrannini  4
Affiliations
Clinical Trial

Tirzepatide Treatment and Associated Changes in β-Cell Function and Insulin Sensitivity in People With Obesity or Overweight With Prediabetes or Normoglycemia: A Post Hoc Analysis From the SURMOUNT-1 Trial

Andrea Mari et al. Diabetes Care. .

Abstract

Objective: We assessed insulin sensitivity and β-cell function in adults with obesity/overweight, without diabetes, treated with tirzepatide for 72 weeks.

Research design and methods: This post hoc analysis from the Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1) trial investigated tirzepatide versus placebo in 2,539 participants with BMI ≥27 kg/m2 and either prediabetes or normoglycemia at baseline. Model-derived parameters of β-cell function and insulin sensitivity were assessed from oral glucose tolerance tests.

Results: At week 72, tirzepatide treatment was associated with body weight reduction and improvements in insulin sensitivity and β-cell function measures overall and in participants with prediabetes or normoglycemia. In multivariate regression models, improvements in insulin sensitivity were associated mostly with weight reduction and partly with tirzepatide treatment, whereas enhancement in β-cell function was mostly associated with tirzepatide treatment.

Conclusions: In adults with obesity/overweight without type 2 diabetes, tirzepatide treatment was associated with improved β-cell function and insulin sensitivity, partly independent of weight reduction.

PubMed Disclaimer

Conflict of interest statement

Duality of Interest. This study was sponsored by Eli Lilly and Company. Eli Lilly and Company was involved in the study design and conduct; data collection, management, analyses, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The sponsor did not have the right to veto publication or to control the decision regarding which journal the manuscript was chosen for submission. Final decisions resided with the authors, which included employees of the sponsor. A.S., X.M., E.S.L., L.F., C.J.L., M.K.T., and M.C.B. are employees and shareholders of Eli Lilly and Company. M.K.T. has a patent pending as an inventor and serves on the steering committee of the Accelerating Medicines Partnership in Common Metabolic Diseases. E.S.L. also holds stock and has received dividends from Johnson and Johnson, Novartis, Novo Nordisk, Pfizer, Proctor and Gamble, and Sandoz Group. A.M. has received consulting fees and support for attending meetings and/or travel from Eli Lilly and Company. D.H.v.R. has received grants or contracts from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, and MSD, and received consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, MSD, and Novo Nordisk. E.F. has received consulting fees from Boehringer Ingelheim, Eli Lilly and Company, and Janssen; payment or honoraria for speaking/lectures/presentations from Boehringer Ingelheim and Eli Lilly and Company; and serves on the Scientific Advisory Board for Eli Lilly and Company and Oramed. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Changes in glucose AUC (A) and insulin AUC (B) at week 72 from baseline for the overall SURMOUNT-1 study population and by glycemic status at baseline. Data are least-squares (LS) mean ± SE. For both outcomes, changes were significantly greater with tirzepatide compared with placebo, irrespective of glycemic status (P < 0.001).
Figure 2
Figure 2
Changes in modeled β-GS (A) and ISR at 5.4 mmol/L glucose (B) at week 72 from baseline for the overall SURMOUNT-1 study population and by glycemic status at baseline. Data are least-squares (LS) mean ± SE. For both outcomes, changes were significantly greater for all tirzepatide groups compared with placebo, irrespective of glycemic status (P < 0.05), except for β-GS in participants with prediabetes treated with tirzepatide 5 mg (P = ns).
Figure 3
Figure 3
Changes in the Matsuda index (A) and OGIS (B) at week 72 from baseline for the overall SURMOUNT-1 study population and by glycemic status at baseline. Data are least-squares (LS) mean ± SE. For both outcomes, changes were significantly greater with tirzepatide compared with placebo, irrespective of glycemic status (P < 0.001).
See this image and copyright information in PMC

References

    1. Jastreboff AM, Aronne LJ, Ahmad NN, et al. ; SURMOUNT-1 Investigators . Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022;387:205–216 - PubMed
    1. Thomas MK, Nikooienejad A, Bray R, et al. Dual GIP and GLP-1 receptor agonist tirzepatide improves beta-cell function and insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab 2021;106:388–396 - PMC - PubMed
    1. Lee CJ, Mao H, Thieu VT, Landó LF, Thomas MK.. Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1). J Endocr Soc 2023;7:bvad056. - PMC - PubMed
    1. Heise T, Mari A, DeVries JH, et al. Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet Diabetes Endocrinol 2022;10:418–429 - PubMed
    1. American Diabetes Association . 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes—2019. Diabetes Care 2019;42(Suppl. 1):S13–S28 - PubMed

Publication types

MeSH terms

Grants and funding