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Review
. 2023 Oct 30;15(1):222.
doi: 10.1186/s13098-023-01198-4.

Efficacy and safety of tirzepatide, dual GLP-1/GIP receptor agonists, in the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Qian Zhou  1   2 , Xingxing Lei  1   2 , Shunlian Fu  1 , Pan Liu  1 , Cong Long  1 , Yanmei Wang  3 , Zinan Li  1   4 , Qian Xie  1 , Qiu Chen  5
Affiliations
Review

Efficacy and safety of tirzepatide, dual GLP-1/GIP receptor agonists, in the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Qian Zhou et al. Diabetol Metab Syndr. .

Abstract

Background: Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are the main incretin hormones, and be responsible for the insulinotropic incretin effect. The addition of a GIP agonist to a GLP-1agonist has been hypothesized to significantly potentiate the weight-losing and glycemia control effect, which might offer a new therapeutic option in the treatment of type 2 diabetes. The current meta-analysis aims to synthesize evidence of primary efficacy and safety outcomes through clinically randomized controlled trials to evaluate integrated potency and signaling properties.

Method: We conducted comprehensive literature searches in Cochrane Library, Web of Science, Embase and PubMed for relevant literatures investigating the efficacy and/or safety of Tirzepatide published in the English as of May 30, 2023 was retrieved. We synthesized results using standardized mean differences (SMDs) and 95% confidence intervals (95 CIs) for continuous outcomes, and odds ratios (ORs) along with 95 Cis for dichotomous outcomes. All analyses were done using Revman version 5.3, STATA version 15.1 and the statistical package 'meta'.

Results: Participants treated with weekly Tirzepatide achieved HbA1c and body weight target values significantly lower than any other comparator without clinically significant increase in the incidence of hypoglycemic events, serious and all-cause fatal adverse events. However, gastrointestinal adverse events and decreased appetite events were reported more frequently with Tirzepatide treatment than with placebo/controls.

Conclusion: The Tirzepatide, a dual GIP/GLP-1 receptor co-agonist, for diabetes therapy has opened a new era on personalized glycemia control and weight loss in a safe manner with broad and promising clinical implications.

Keywords: Dual GIP/GLP-1 receptor agonist; GLP-1 receptor agonists; Meta-analysis; Tirzepatide; Type 2 diabetes.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Flowchart of literature search
Fig. 2
Fig. 2
Overall summary of risk of bias in the included studies. + : low risk of bias; −: high risk of bias; ?: unclear risk of bias
Fig. 3
Fig. 3
Summary of quantitative data analysis with Random effects or fixed effects SMD (95% CI) estimate with a p-value for analysis of primary efficacy outcomes. *Statistically significant variables at P value < 0.05. a Fasting serum glucose, b hemoglobin A1c, c body weight, d triglyceride, e HDL cholesterol, f LDL cholesterol
Fig. 4
Fig. 4
Summary of count data analysis with random effects or fixed effects ORs (95% CI) estimate with a p-value for analysis of primary safety outcomes. *Statistically significant variables at P value < 0.05. a All adverse events, b gastrointestinal events, c decreased appetite, d hypoglycemic events, e discontinuation of therapy, f serious adverse events, g fatal adverse event
See this image and copyright information in PMC

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