Tirzepatide is a novel once-a-week dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, currently under trial to assess glycemic efficacy and safety in people with type 2 diabetes. A systematic review and meta-analysis were conducted to investigate the efficacy of tirzepatide on glycated hemoglobin (HbA1c, %), fasting serum glucose (mg/dL), and body weight (kg) in patients with uncontrolled type 2 diabetes (HbA1c > 7.0%). Mean changes for efficacy and proportions (safety) with corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of four randomized controlled trials, comprising 2783 patients of whom 69.4% (n = 1934) were treated with 5 mg (n = 646), 10 mg (n = 641), or 15 mg (n = 647) of tirzepatide, were compared to the placebo (n = 192) or the selective GLP-1 receptor agonist (n = 523). The pooled analysis showed that tirzepatide treatment resulted in a greater lowering of the HbA1c (-1.94%, 95% CI: -2.02 to -1.87), fasting serum glucose (-54.72 mg/dL, 95% CI: -62.05 to -47.39), and body weight (-8.47, 95% CI: -9.66 to -7.27). We also found that improvement in the HbA1c levels was still maintained at weeks 26 and 40 from the long-term trials. As for safety, only 3% experienced hypoglycemia, and 4% (95% CI: 2 to 6) experienced serious adverse events, while the discontinuation of therapy percentage was 7% (95% CI: 5 to 8). Tirzepatide significantly improved glycemic control and body weight and had an acceptable safety profile, indicating that it is an effective therapeutic option for glucose-lowering in patients with type 2 diabetes mellitus.

Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Králové Charles University 50115 Hradec Králové Czech Republic

Health Research Institute University of Canberra Canberra ACT 2617 Australia

University College of Pharmaceutical Sciences Kakatiya University Warangal 506009 India

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Saeedi P., Petersohn I., Salpea P., Malanda B., Karuranga S., Unwin N., Colagiuri S., Guariguata L., Motala A.A., Ogurtsova K., et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res. Clin. Pract. 2019;157:7843. doi: 10.1016/j.diabres.2019.107843. PubMed DOI

Gerstein H., Pogue J., Mann J., Lonn E., Dagenais G., McQueen M., Yusuf S. The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: A prospective epidemiological analysis. Diabetologia. 2005;48:1749–1755. doi: 10.1007/s00125-005-1858-4. PubMed DOI

Bailes B.K. Diabetes mellitus and its chronic complications. AORN J. 2002;76:265–282. doi: 10.1016/S0001-2092(06)61065-X. PubMed DOI

Colagiuri S. Optimal management of type 2 diabetes: The evidence. Diabetes Obes. Metab. 2012;14:3–8. doi: 10.1111/j.1463-1326.2011.01506.x. PubMed DOI

Min T., Bain S.C. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. Res. Treat. Educ. Diabetes Relat. Disord. 2021;12:143–157. doi: 10.1007/s13300-020-00981-0. PubMed DOI PMC

Palmer S.C., Tendal B., Mustafa R.A., Vandvik P.O., Li S., Hao Q., Tunnicliffe D., Ruospo M., Natale P., Saglimbene V., et al. Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: Systematic review and network meta-analysis of randomised controlled trials. BMJ. 2021;372:m4573. doi: 10.1136/bmj.m4573. PubMed DOI PMC

Andersen A., Lund A., Knop F.K., Vilsbøll T. Glucagon-like peptide 1 in health and disease. Nat. Rev. Endocrinol. 2018;14:390–403. doi: 10.1038/s41574-018-0016-2. PubMed DOI

Holst J.J., Rosenkilde M.M. GIP as a Therapeutic Target in Diabetes and Obesity: Insight from Incretin Co-agonists. J. Clin. Endocrinol. Metab. 2020;105:e2710–e2716. doi: 10.1210/clinem/dgaa327. PubMed DOI PMC

Coskun T., Sloop K.W., Loghin C., Alsina-Fernandez J., Urva S., Bokvist K.B., Cui X., Briere D.A., Cabrera O., Roell W.C., et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol. Metab. 2018;18:3–14. doi: 10.1016/j.molmet.2018.09.009. PubMed DOI PMC

Frías J.P. Tirzepatide: A glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes. Expert. Rev. Endocrinol. Metab. 2020;15:379–394. doi: 10.1080/17446651.2020.1830759. PubMed DOI

Nauck M., Bartels E., Orskov C., Ebert R., Creutzfeldt W. Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. J. Clin. Endocrinol. Metab. 1993;76:912–917. doi: 10.1210/jcem.76.4.8473405. PubMed DOI

Elahi D., McAloon-Dyke M., Fukagawa N.K., Meneilly G.S., Sclater A.L., Minaker K.L., Habener J.F., Andersen D.K. The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7–37) in normal and diabetic subjects. Regul. Pept. 1994;51:63–74. doi: 10.1016/0167-0115(94)90136-8. PubMed DOI

Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. PubMed DOI PMC

Sterne J.A.C., Savovic J., Page M.J., Elbers R.G., Blencowe N.S., Boutron I., Cates C.J., Cheng H.Y., Corbett M.S., Eldridge S.M., et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898. PubMed DOI

Cumpston M., Li T., Page M.J., Chandler J., Welch V.A., Higgins J.P., Thomas J. 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. doi: 10.1002/14651858.ED000142. PubMed DOI PMC

Higgins J., Thomas J. Cochrane Handbook for Systematic Reviews of Interventions. 2019. [(accessed on 27 July 2021)]. Available online: https://training.cochrane.org/handbook/current.

Rosenstock J., Wysham C., Frías J.P., Kaneko S., Lee C.J., Fernández Landó L., Mao H., Cui X., Karanikas C.A., Thieu V.T. 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. 2021;398:143–155. doi: 10.1016/S0140-6736(21)01324-6. PubMed DOI

Frias J.P., Nauck M.A., Van J., Kutner M.E., Cui X., Benson C., Urva S., Gimeno R.E., Milicevic Z., Robins D., et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: A randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018;392:2180–2193. doi: 10.1016/S0140-6736(18)32260-8. PubMed DOI

Frias J.P., Nauck M.A., Van J., Benson C., Bray R., Cui X., Milicevic Z., Urva S., Haupt A., Robins D.A. Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens. Diabetes Obes. Metab. 2020;22:938–946. doi: 10.1111/dom.13979. PubMed DOI PMC

Frías J.P., Davies M.J., Rosenstock J., Pérez Manghi F.C., Fernández Landó L., Bergman B.K., Liu B., Cui X., Brown K. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N. Engl. J. Med. 2021;385:503–515. doi: 10.1056/NEJMoa2107519. PubMed DOI

Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42:S90–S102. doi: 10.2337/dc19-S009. PubMed DOI

Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44:S111–S124. doi: 10.2337/dc21-S009. PubMed DOI

Gault V.A., Kerr B.D., Harriott P., Flatt P.R. Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity. Clin. Sci. 2011;121:107–117. doi: 10.1042/CS20110006. PubMed DOI

ClinicalTrials.gov. [(accessed on 31 August 2021)]; Available online: https://clinicaltrials.gov/ct2/show/NCT04657016.

A Study of Tirzepatide (LY3298176) in Participants with Obesity or Overweight for the Maintenance of Weight Loss (SURMOUNT-4) [(accessed on 31 August 2021)]; Available online: https://clinicaltrials.gov/ct2/show/NCT04660643.

A Study of Tirzepatide (LY3298176) In Participants after a Lifestyle Weight Loss Program (SURMOUNT-3) [(accessed on 31 August 2021)]; Available online: https://clinicaltrials.gov/ct2/show/NCT04657016.

A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants with Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) with or without Metformin (SURPASS-6) [(accessed on 31 August 2021)]; Available online: https://clinicaltrials.gov/ct2/show/NCT04537923.

A Study of Tirzepatide in Participants with Type 2 Diabetes Mellitus (T2DM) [(accessed on 31 August 2021)]; Available online: https://clinicaltrials.gov/ct2/show/NCT03951753.

A Study of Tirzepatide (LY3298176) in Participants with Type 2 Diabetes Who Have Obesity or Are Overweight (SURMOUNT-2) [(accessed on 31 August 2021)]; Available online: https://clinicaltrials.gov/ct2/show/NCT04657003.

Sun F., Chai S., Yu K., Quan X., Yang Z., Wu S., Zhang Y., Ji L., Wang J., Shi L. Gastrointestinal adverse events of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: A systematic review and network meta-analysis. Diabetes Technol. Ther. 2015;17:35–42. doi: 10.1089/dia.2014.0188. PubMed DOI PMC

A Study of Tirzepatide (LY3298176) Compared with Dulaglutide on Major Cardiovascular Events in Participants with Type 2 Diabetes (SURPASS-CVOT) [(accessed on 31 August 2021)];2020 Available online: https://clinicaltrials.gov/ct2/show/NCT04255433.

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