Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 6;15(1):24103.
doi: 10.1038/s41598-025-09807-0.

Efficacy and safety of GLP-1 agonists in the treatment of T2DM: A systematic review and network meta-analysis

Xiaoyu Ren  1 , Honghao Hua  2 , Yuanqin Wu  2 , Wei Zhang  1 , Xianzhen Long  2 , Yana Bai  2 , Ning Cheng  3
Affiliations

Efficacy and safety of GLP-1 agonists in the treatment of T2DM: A systematic review and network meta-analysis

Xiaoyu Ren et al. Sci Rep. .

Abstract

To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in subjects with type 2 diabetes (T2DM). Electronic databases were searched from inception to 2nd October 2024 for randomised controlled trials comparing GLP-1RAs treating T2DM. Bayesian network meta-analyses were conducted to analyze metabolic and safety outcomes. 64 trials comprising of 25,572 participants were identified. Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05). All treatments showed no statistically significant differences in BMI, SBP, DBP, TC, HDL-C and LDL-C compared to placebo. Tirzepatide (MD: -9.1 kg), semaglutide (MD: -2.8 kg) and liraglutide (MD: -1.2 kg) (P<0.05) had significant reduction in body weight compared to placebo. GLP-1 RAs had higher risk of gastrointestinal symptoms. Semaglutide increased the risk of hypoglycemia compared to placebo while liraglutide reduced the risk of hypoglycemia compared to traditional antidiabetic drugs. GLP-1RAs improve glycaemic control, with tirzepatide, semaglutide and liraglutide exhibiting the most significant improvements. Tirzepatide is more suitable for treating T2DM with obesity. For individuals with normal weight, both semaglutide and liraglutide are generally more effective for treating T2DM. However, considering the potential for semaglutide to cause hypoglycemia, liraglutide may be the optimal choice for T2DM treatment to minimize the risk of hypoglycemia.

Keywords: Glucagon-like peptide-1 receptor agonists; Network meta-analysis; Type 2 diabetes mellitus.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the systematic search and selection process.
Fig. 2
Fig. 2
The distribution for each risk of bias item and risk of bias items for each study.
Fig. 3
Fig. 3
Network plot for primary outcomes.
Fig. 4
Fig. 4
NMA results for the mean difference in HbA1c (%) in comparison to placebo and traditional antidiabetic drugs.
Fig. 6
Fig. 6
NMA results for the mean difference in primary outcomes in comparison to placebo and traditional antidiabetic drugs.
Fig. 5
Fig. 5
NMA results for the mean difference in FPG (mmol/L) in comparison to placebo and traditional antidiabetic drugs.
See this image and copyright information in PMC

References

    1. Tao, Y. W., Gu, Y. L., Mao, X. Q., Zhang, L. & Pei, Y. F. Effects of probiotics on type II diabetes mellitus: a meta-analysis. 18(1):30. (2020). - PMC - PubMed
    1. Magliano, D. J., Boyko, E. J. & committee IDFDAtes. IDF Diabetes Atlas. Idf diabetes atlas. Brussels: International Diabetes Federation © International Diabetes Federation, ; 2021. (2021).
    1. Li, Y., Gao, S., Zhang, R. & Li, B. Y. Research progress on clinical application and mechanism of action of liraglutide. Mod. Med. Clin.37 (01), 197–202 (2022).
    1. Lovshin, J. A. Glucagon-like Peptide-1 receptor agonists: A class update for treating type 2 diabetes. Can. J. Diabetes. 41 (5), 524–535 (2017). - PubMed
    1. Boarder, M. et al. Pharmacology for Pharmacy and the Health Sciences: a patient-centred Approach (Oxford University Press, 2017).

Publication types

MeSH terms