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Effectiveness of GLP-1 RAs and SGLT2 inhibitors in preventing T2DM in high-risk patients: an updated systematic review and meta-analysis

Tsironikos GI, Tsolaki V, Zakynthinos GE, Kyprianidou D, Rammou V, Antonogiannis T, Mprotsis T, Zakynthinos E et al.

Frontiers in clinical diabetes and healthcare, 2025

24,157 participants · 2 citations

Abstract

Introduction: There are conflicting results and limited data regarding the individual effectiveness of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors and their combined action in preventing type 2 diabetes mellitus (T2DM) in high-risk adults. An updated investigation is warranted. We aimed to explore their effectiveness in preventing T2DM in high-risk patients and assess changes in body weight/body mass index (BMI), glycemic parameters, and safety.

Materials and methods: PubMed, Cochrane Library Central Register of Controlled Trials, and Scopus were searched for eligible randomized controlled trials (RCTs), and a systematic review (SR) and meta-analysis (MA) were conducted. GRADE assessment was conducted for rating the overall certainty of evidence.

Results: All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese. Compared to placebo, GLP-1 RAs reduced T2DM incidence (OR 0.51; 95% CI 0.28, 0.94; P-value 0.03), and 2.4 mg of semaglutide was overall effective (OR 0.38; 95% CI 0.16, 0.94; P-value P-value I² 84%, 95% CI 74%, 89%), and MA was performed using the random-effects model. Heterogeneity was explained by countries' performance in semaglutide- and liraglutide-based RCTs and participants' mean age, dosage, duration, and post-intervention evaluation in liraglutide-based RCTs. Sensitivity analyses considering studies with post-intervention assessment and studies with the largest sample size and dropout…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 24,157 participants or records.

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