Abstract
In this systematic review and meta-analysis, we compared the efficacy and safety of tirzepatide with those of long-acting or ultra-long-acting insulin for type 2 diabetes. PubMed, Web of Science, Scopus, and Google Scholar were searched from the inception to August 20, 2023. All clinical trials or randomized clinical trials comparing the efficacy of tirzepatide with long-acting or ultra-long-acting insulin for treating type 2 diabetes were included. Three randomized clinical trials, namely SURPASS-3, SURPASS-4, and SURPASS-AP-Combo, with 4339 patients were included. Compared with daily insulin glargine and degludec, once-weekly tirzepatide significantly decreased HbA1c (WMD −1.08%, 95% CI (−1.37, −0.78)), 2h-posprandial blood sugar (BS) (WMD −28.19 mg/dL, 95% CI (−44.98, −11.41)), pre-meal BS (WMD −11.86 mg/dL, 95% CI (−22.83, −0.9)), body weight (WMD −10.61 kg, 95% CI (−13.24, −7.97)), systolic blood pressure (WMD −6.47 mmHg, 95% CI (−8.32, −4.61)), diastolic blood pressure (WMD −2.30 mmHg, 95% CI (−3.05, −1.55)), total cholesterol (WMD −4.78%, 95% CI (−7.05, −2.50)), triglyceride (WMD −14.49%, 95% CI (−19.55, −9.43)), LDL cholesterol (WMD −5.98%, 95% CI (−9.83, −2.13)), and VLDL cholesterol (WMD −14.18%, 95% CI (−19.03, −9.33)) and increased HDL cholesterol (WMD 7.13%, 95% CI (−9.83, −2.13)), with a lower risk of hypoglycemia defined as BS ≤ 70 mg/dL (RR 0.46, 95% CI (0.28, 0.75)). All doses of once-weekly tirzepatide (5 mg, 10 mg, and 15 mg) were superior or non-inferior to insulin. Once-weekly tirzepatide can be a substitution for long-acting insulin in type 2 diabetes with a greater efficacy.
This is a preview of subscription content, access via your institution
Access options
Change institution
Buy or subscribe
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Learn more
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials
Article 17 July 2023
Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial
Article 25 May 2023
Cardiovascular safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas in type 2 diabetes: systematic review and meta-analysis of randomized controlled trials
Article Open access 08 January 2021
References
GBD 2019 Diabetes in the Americas Collaborators. Burden of diabetes and hyperglycaemia in adults in the Americas, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Diabetes Endocrinol. 2022;10:655–67. https://doi.org/10.1016/S2213-8587(22)00186-3.
Safiri S, Karamzad N, Kaufman JS, Bell AW, Nejadghaderi SA, Sullman MJM, et al. Prevalence, deaths and disability-adjusted-life-years (DALYs) due to type 2 diabetes and its attributable risk factors in 204 countries and territories, 1990-2019: results from the global burden of disease study 2019. Front Endocrinol. 2022;13:838027.
Dahlén AD, Dashi G, Maslov I, Attwood MM, Jonsson J, Trukhan V, et al. Trends in antidiabetic drug discovery: FDA approved drugs, new drugs in clinical trials and global sales. Front Pharmacol. 2021;12:807548.
Gao L, Lee BW, Chawla M, Kim J, Huo L, Du L, et al. Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial. Nat Med. 2023;29:1500–10.
Ludvik B, Giorgino F, Jódar E, Frias JP, Fernández Landó L, Brown K, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet (Lond, Engl). 2021;398:583–98.
Heise T, DeVries JH, Urva S, Li J, Pratt EJ, Thomas MK, et al. Tirzepatide reduces appetite, energy intake, and fat mass in people with type 2 diabetes. Diab Care. 2023;46:998–1004.
Seino Y, f*ckushima M, Yabe D. GIP and GLP-1, the two incretin hormones: similarities and differences. J Diab Investig. 2010;1:8–23.
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205–16.
Bhagavathula AS, Vidyasagar K, Tesfaye W. Efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized phase II/III trials. Pharm (Basel, Switz). 2021;14:991.
CAS Google Scholar
Kiyosue A, Dunn JP, Cui X, Hickey A, Hirase T, Imaoka T, et al. Safety and efficacy analyses across age and body mass index subgroups in East Asian participants with type 2 diabetes in the phase 3 tirzepatide studies (SURPASS programme). Diab Obes Metab. 2023;25:1056–67.
Gastaldelli A, Cusi K, Fernández Landó L, Bray R, Brouwers B, Rodríguez Á. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diab Endocrinol. 2022;10:393–406.
Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet (Lond, Engl). 2021;398:143–55.
Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503–15.
Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA. 2022;327:534–45.
Inagaki N, Takeuchi M, Oura T, Imaoka T, Seino Y. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet Diab Endocrinol. 2022;10:623–33.
Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet (Lond, Engl). 2023;402:613–26.
Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet (Lond, Engl). 2021;398:1811–24.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906.
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Clin Res ed). 2019;366:l4898.
Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane database Syst Rev. 2019;10:Ed000142.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.
Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.
Thomas MK, Nikooienejad A, Bray R, Cui X, Wilson J, Duffin K, 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;106:388–96.
Kristensen FPB, Christensen DH, Callaghan BC, Stidsen JV, Nielsen JS, Højlund K, et al. The prevalence of polyneuropathy in type 2 diabetes subgroups based on HOMA2 Indices of β-cell function and insulin sensitivity. Diab Care. 2023;46:1546–55.
Lingvay I, Cheng AY, Levine JA, Gomez-Valderas E, Allen SE, Ranta K, et al. Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: a post hoc analysis of the SURPASS-1 to −5 studies. Diab Obes Metab. 2023;25:965–74.
Viljoen A, Pantalone KM, Galindo RJ, Cui X, Huh R, Hemmingway A, et al. Time to reach glycaemic and body weight loss thresholds with tirzepatide in patients with type 2 diabetes: a pre-planned exploratory analysis of SURPASS-2 and SURPASS-3. Diab Ther: Res Treat Educ Diab Relat Disord. 2023;14:925–36.
Pedersen SD, Giorgino F, Umpierrez G, Thieu VT, Rodríguez A, Nicolay C, et al. Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: a post hoc assessment of the SURPASS clinical trial programme. Diab Obes Metab. 2023;25:2553–60.
Wilson JM, Nikooienejad A, Robins DA, Roell WC, Riesmeyer JS, Haupt A, et al. The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes. Diab Obes Metab. 2020;22:2451–9.
Lingvay I, Mosenzon O, Brown K, Cui X, O’Neill C, Fernández Landó L, et al. Systolic blood pressure reduction with tirzepatide in patients with type 2 diabetes: insights from SURPASS clinical program. Cardiovascular Diabetol. 2023;22:66.
Li S, Liu Z, Joseph P, Hu B, Yin L, Tse LA, et al. Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy. Eur Heart J. 2022;43:2852–63.
Author information
Authors and Affiliations
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Moein Ala,Razieh Mohammad Jafari&Ahmad Reza Dehpour
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
Moein Ala,Razieh Mohammad Jafari&Ahmad Reza Dehpour
Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Poursalehian
Authors
- Moein Ala
View author publications
You can also search for this author in PubMedGoogle Scholar
- Razieh Mohammad Jafari
View author publications
You can also search for this author in PubMedGoogle Scholar
- Ahmad Reza Dehpour
View author publications
You can also search for this author in PubMedGoogle Scholar
- Mohammad Poursalehian
View author publications
You can also search for this author in PubMedGoogle Scholar
Contributions
MA conceptualized this article, performed the literature search, reviewed the retrieved articles, analyzed data, wrote the draft, edited the draft, and designed the figures. MP performed the literature search, and reviewed the retrieved articles. RMJ and ARD critically edited the article. All authors had full access to data and approved the last version of this article for publication.
Corresponding author
Correspondence to Moein Ala.
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Ala, M., Mohammad Jafari, R., Dehpour, A.R. et al. Tirzepatide outcompetes long-acting insulin in managing type 2 diabetes: a meta-analysis of three phase 3 randomized controlled trials. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01621-4
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41366-024-01621-4
