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The efficacy and safety of combinations of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes or obese adults: a systematic review and meta-analysis

Abstract

Purpose

To evaluate the efficacy and safety of combination therapy with sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM) or obese adults.

Methods

A meta-analysis was conducted of trials by searching in PubMed, Embase, CENTRAL, Web of Science, and Scopus.

Results

A total of five randomized controlled trials (RCTs) and six nonrandomized controlled trials (NCTs) enrolled 1604 participants were identified for meta-analysis. Compared with control/placebo, the combination therapy group had significantly reduced fasting plasma glucose level and 2 h postprandial glucose by 1.28 mmol/L (95% confidence interval [CI]: −1.39, −1.16; p < 0.001) and 1.34 mmol/L (95% CI: −1.47, −1.21; p < 0.001); glycosylated hemoglobin (HbA1c) by 1.32% (95% CI: −1.43, −1.20; p < 0.001); body weight by 0.93 kg (95% CI: −1.04, −0.83; p < 0.001), and systolic blood pressure (SBP) by 1.05 mmHg (95% CI: −1.17, −0.93; p < 0.001). The incidence of genital mycotic infections and urinary infections did not significantly differ from those in the control group, with relative risks (RRs) of 1.67 (95% CI: 0.85, 3.27; p = 0.651) and 1.25 (95% CI: 0.73, 2.15; p = 0.905), respectively. A decreased incidence of cardiovascular events was seen in the combination therapy group (RR = 0.19; 95% CI: 0.04, 0.96; p = 0.403), while an incidence of hypoglycemia was reported (RR = 2.22; 95% CI: 1.20, 4.10; p = 0.71).

Conclusions

SGLT2 inhibitors and GLP-1 agonists combination treatment improved glycemic control, reduced body weight, and decreased SBP without an increase in total adverse events or genital and urinary infections in patients with T2DM or obesity.

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Author contributions

M.G. and Y.X. participated in the study conception and design. M.G. and J.G. acquired reports of trials and extracted data. M.G., F.T., and X.M. performed data analyses. J.C., Q.C., and Y.P. checked for statistical consistency. M.G., J.G., and F.T. contributed to data interpretation and drafted the paper. Y.X., Y.L., and Z.J. critically reviewed the paper. M.G., J.G., and Y.X. contributed to the discussion, were guarantors of this work, had full access to all data in the study, and took responsibility for the integrity and accuracy of the data analysis. All authors approved the final version of this paper.

Funding

This study was funded by grants from the National Natural Science Foundation of Chian (grant number 81800741) and Luzhou-Southwest Medical University cooperation project (grant number 2016LZXNYD-G02).

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Correspondence to Yong Xu.

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The authors gratefully acknowledge BioMed Proofreading for English expression polished and declare that they have no conflict of interest.

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Guo, M., Gu, J., Teng, F. et al. The efficacy and safety of combinations of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes or obese adults: a systematic review and meta-analysis. Endocrine 67, 294–304 (2020). https://doi.org/10.1007/s12020-019-02175-6

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Keywords

  • SGLT2 inhibitors
  • GLP-1 agonists
  • Type 2 diabetes mellitus
  • Obesity
  • Meta-analysis