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Effectiveness of GLP-1 RAs and SGLT2 inhibitors in preventing T2DM in high-risk patients: an updated systematic
Georgios I Tsironikos1, Vasiliki Tsolaki2, George E Zakynthinos3
1Department of Research for General Medicine and Primary Health Care, Faculty of Medicine, University of Ioannina, Ioannina, Greece.
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 < 0.0001). Subgroup analysis indicated effectiveness in patients more than 50 years across the world, in cardiovascular disease, after 100 weeks, and during the post-intervention period. Liraglutide was not overall effective. However, subgroup analyses demonstrated effectiveness for studies that were performed worldwide, for women more than 40 years, at 3.0 mg daily, after 55 weeks of administration, and only during intervention. Exenatide was not effective. Heterogeneity was large (Q 54.56, P-value < 0.0001; 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 rate more than 5% in semaglutide-based RCTs explain further heterogeneity. The quality of evidence was low. Compared to placebo, GLP-1 RAs reduced weight (kg) and BMI (kg/m²) (mean difference -6.35, P-value < 0.00001 and -2.46, P-value < 0.00001, respectively). Finally, GLP-1 RAs were safe (OR for adverse events 1.01; P-value 0.95).
Conclusions:
GLP-1 RAs may prevent diabetes in high-risk adults and ameliorate body and glycemic factors. Their effectiveness should be considered carefully due to the low quality of evidence. No safety issues were identified. Future investigation is necessary to provide consistency of estimations.
Systematic Review Registration:
OSF Registration, identifier DOI 10.17605/OSF.IO/8XH4.
Insights
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) show potential in preventing type 2 diabetes mellitus in high-risk adults, improving weight and glycemic control. However, evidence quality is low, necessitating further research for consistent findings.
Area of Science:
- Endocrinology and Metabolism
- Pharmacology
- Preventive Medicine
Background:
- Conflicting data exists on the effectiveness of GLP-1 RAs and SGLT2 inhibitors for T2DM prevention in high-risk adults.
- An updated investigation is needed to clarify their individual and combined roles.
- Focus on high-risk adults requires assessment of weight, glycemic parameters, and safety.
Purpose of the Study:
- To explore the effectiveness of GLP-1 RAs in preventing T2DM in high-risk individuals.
- To assess the impact of GLP-1 RAs on body weight, BMI, and glycemic parameters.
- To evaluate the safety profile of GLP-1 RAs in this population.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (RCTs) from PubMed, Cochrane Library, and Scopus.
- Inclusion of 24,157 participants from 10 GLP-1 RA RCTs.
- GRADE assessment was used to rate the certainty of evidence.
Main Results:
- GLP-1 RAs significantly reduced T2DM incidence (OR 0.51) compared to placebo, with semaglutide showing notable effectiveness (OR 0.38).
- GLP-1 RAs led to significant reductions in body weight (MD -6.35 kg) and BMI (MD -2.46 kg/m²).
- GLP-1 RAs demonstrated a favorable safety profile (OR 1.01 for adverse events), though evidence quality was low.
Conclusions:
- GLP-1 RAs may offer benefits in preventing T2DM and improving metabolic factors in high-risk adults.
- Effectiveness varies by agent (semaglutide effective, liraglutide and exenatide less so in certain contexts).
- Low quality of evidence necessitates cautious interpretation and further research for consistent results.
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