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Updated: Jan 31, 2026
Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
The effect of GLP-1 receptor agonist and SGLT2 inhibitor on infection risk: network meta-analysis
Bing-Syuan Zeng1, Jiann-Jy Chen2, Chih-Wei Hsu3
1Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
Background:
Patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose co-transporter 2 (SGLT2) inhibitors often have underlying conditions that predispose them to infection. While these agents offer cardiometabolic benefits, concerns persist regarding their impact on infectious risk. Existing literature has not comprehensively assessed their dose-dependent influence on severe infections such as sepsis.
Objectives:
To investigate the effect of GLP-1 receptor agonists and SGLT2 inhibitors on infection risk.
Data Sources:
PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov up to December 18, 2024.
Study Eligibility Criteria:
Randomized controlled trials reporting target infection outcomes related to GLP-1 receptor agonists or SGLT2 inhibitor prescription.
Participants:
Individuals without evidence of ongoing infection at study initiation.
Interventions:
GLP-1 receptor agonists or SGLT2 inhibitors.
Assessment Of Risk Of Bias:
Cochrane risk of bias tool version 2.0.
Methods Of Data Synthesis:
A frequentist random-effects model was used to assess the comparative incidence of infectious complications-classified as sepsis, abscess/gangrene, or other infections (e.g., pneumonia and urinary tract infection). Drop-out rates served to reflect acceptability. Sensitivity analyses included Bayesian modelling and subgroup analyses of diabetic status and treatment duration.
Results:
Based on 105 randomized controlled trials with 219 283 participants, no significant association was found between GLP-1 receptor agonists or SGLT2 inhibitors and controls, except for high-dose canagliflozin (300 mg/day), which was the only intervention significantly associated with reduced sepsis risk versus control. This effect persisted in participants with diabetes. No significant associations were found between any other GLP-1 receptor agonist or SGLT2 inhibitor and risk of sepsis, abscess, gangrene, or other infections. Subgroup and meta-regression analyses confirmed robustness. Bayesian modelling yielded comparable results. Treatment duration had minimal influence on primary outcomes.
Conclusions:
This analysis identifies no significant evidence of infection-related adverse events related to GLP-1 receptor agonist or SGLT2 inhibitor prescription.
Insights
Glucagon-like peptide-1 (GLP-1) receptor agonists and SGLT2 inhibitors generally do not increase infection risk. High-dose canagliflozin showed a potential benefit in reducing sepsis risk, particularly in diabetic patients.
Area of Science:
- Pharmacology and Therapeutics
- Infectious Disease Epidemiology
- Cardiometabolic Medicine
Background:
- Patients on GLP-1 receptor agonists and SGLT2 inhibitors often have comorbidities increasing infection susceptibility.
- While offering cardiometabolic advantages, these drug classes raise concerns about infectious risks.
- Dose-dependent effects on severe infections like sepsis remain incompletely understood.
Purpose of the Study:
- To evaluate the association between GLP-1 receptor agonists, SGLT2 inhibitors, and the risk of infections.
- To specifically assess the impact of drug dosage on severe infection outcomes, including sepsis.
Main Methods:
- A systematic review and meta-analysis of 105 randomized controlled trials (RCTs) involving 219,283 participants.
- Inclusion criteria focused on RCTs reporting infection outcomes for GLP-1 receptor agonists or SGLT2 inhibitors.
- Data synthesis employed a frequentist random-effects model, with sensitivity analyses including Bayesian modeling and subgroup analyses.
Main Results:
- No significant increase in infection risk was observed for GLP-1 receptor agonists or SGLT2 inhibitors compared to controls.
- High-dose canagliflozin (300 mg/day) was uniquely associated with a reduced risk of sepsis, an effect seen in diabetic participants.
- No other significant associations were found for sepsis, abscess, gangrene, or other infections across the evaluated agents.
Conclusions:
- Current evidence does not indicate an increased risk of infection-related adverse events with GLP-1 receptor agonists or SGLT2 inhibitors.
- High-dose canagliflozin may offer a protective effect against sepsis, warranting further investigation.
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