Glucagon-like peptide-1 receptor agonists as add-on therapy to insulin for type 1 diabetes mellitus

Xinrui Tan; Xiongfeng Pan; Xiaochuan Wu; Songjia Zheng; Yuyao Chen; Donghai Liu; Xingxing Zhang

doi:10.3389/fphar.2023.975880

Glucagon-like peptide-1 receptor agonists as add-on therapy to insulin for type 1 diabetes mellitus

Front Pharmacol. 2023 Mar 16:14:975880. doi: 10.3389/fphar.2023.975880. eCollection 2023.

Authors

Xinrui Tan¹, Xiongfeng Pan², Xiaochuan Wu¹, Songjia Zheng¹, Yuyao Chen², Donghai Liu¹, Xingxing Zhang¹

Affiliations

¹ Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.

Abstract

Background: To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes. Methods: A search of electronic databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from 1 January 1950 to 23 May 2021 was conducted to find randomized controlled trials. The primary outcome was the change in HbA1c. Eight efficacy and six safety secondary endpoints were evaluated via meta-analysis. Weighted mean difference (WMD) and odds ratio (OR), alongside 95% confidence interval (CI), were calculated using the random effects model. Results: Among 1,379 candidate studies, 11 trials comprising 2,856 participants satisfied the inclusion criteria. Overall, GLP-1 RA adjunctive therapy reduced HbA1c by -0.21% (95% CI, -0.33 to -0.10), weight by -4.04 kg (-4.8 to -3.27), systolic pressure by -2.57 mmHg (-4.11 to -1.03), and diastolic blood pressure by -1.02 mmHg (-1.99 to -0.06). In addition, there was a decrease in prandial insulin dose (WMD, -4.23 IU; 95% CI, -5.26 to -3.20), basal insulin dose (-2.40 IU; -3.93 to -0.87), and total insulin dose (-5.73 IU; -10.61 to -0.86). Moreover, GLP-1 RAs did not increase the incidence of severe hypoglycemia, diabetic ketoacidosis, or severe adverse events. However, GLP-1 RAs increased the incidence of gastrointestinal adverse events (OR, 2.96; 95% CI, 2.33-3.77). Conclusion: Our meta-analysis of randomized clinical trials suggests moderate beneficial effects of GLP-1 RAs on the metabolic profile in patients with type 1 diabetes, without an increased risk of serious adverse events. Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO; Identifier: CRD 42020199840.

Keywords: adjunctive therapy; adult; glucagon-like peptide-1 receptor agonists; meta-analysis; type 1 diabetes.

Publication types

Systematic Review

Grants and funding

The research is financially supported by the Hunan Natural Science Foundation (No.2019JJ50897) and the Hunan Provincial Key Laboratory of Clinical Epidemiology and the Hunan Provincial Key Research and Development Program (2018SK2065), China.