Pharmacological TreatmentsDiabetes Complications

SGLT-2 Inhibitors & GLP-1 Agonists for T2D


The BMJ (British Medical Journal)


SGLT-2 Inhibitors & GLP-1 Agonists for T2D

Summary

This systematic review and network meta-analysis assessed the efficacy and safety of SGLT-2 inhibitors and GLP-1 receptor agonists in patients with Type 2 Diabetes. Both drug classes showed reductions in all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure, with some differences in secondary outcomes.

Study Design

Interventions

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitorsGlucagon-like peptide-1 (GLP-1) receptor agonists

Study Type

Systematic ReviewMeta-AnalysisRCTs

Outcomes

Reduction in heart failure hospitalizationReduction in kidney failureReduction in non-fatal strokeReduction in all-cause mortality

Duration and Size

Long-Term (1–5 y)
Mega size (5000+)

Study Population

Age Range

Middle Aged (40-64)

Sex

MaleFemale

Geography

Global

Other Criteria

with T2 Diabeteswith Cardiovascular Diseasewith Chronic Kidney Disease

Methodology

The study conducted a systematic review and network meta-analysis of randomized controlled trials assessing SGLT-2 inhibitors and GLP-1 receptor agonists in adults with Type 2 Diabetes. It included 764 trials with 421,346 patients and evaluated the effects of these drugs on mortality, cardiovascular events, kidney outcomes, and adverse effects. The review used GRADE certainty assessment and provided absolute effect estimates.

Interventions

Patients were treated with SGLT-2 inhibitors or GLP-1 receptor agonists in addition to their standard diabetes management. The study compared these interventions against placebo or standard care to evaluate their effects on cardiovascular and renal outcomes.

Key Findings

Both SGLT-2 inhibitors and GLP-1 receptor agonists significantly reduced cardiovascular mortality, non-fatal myocardial infarction, and kidney failure. SGLT-2 inhibitors were more effective in reducing hospital admissions for heart failure, while GLP-1 receptor agonists showed stronger effects in lowering non-fatal stroke risk. Genital infections were more frequent with SGLT-2 inhibitors, while GLP-1 receptor agonists had an increased risk of severe gastrointestinal events.

Comparison with other Studies

Several studies have compared the efficacy of SGLT-2 inhibitors and GLP-1 receptor agonists in Type 2 Diabetes (T2D) management, particularly in reducing cardiovascular and renal complications. The BMJ study by Zaccardi et al. (2020) conducted a network meta-analysis, showing that both drug classes lower cardiovascular and kidney disease risks, with SGLT-2 inhibitors excelling in heart failure prevention and GLP-1 receptor agonists showing stronger effects on stroke reduction. Similar findings were reported in a meta-analysis by Zelniker et al. (2019) in Circulation, which highlighted that SGLT-2 inhibitors primarily benefit heart failure and renal outcomes, whereas GLP-1 receptor agonists reduce major atherosclerotic cardiovascular events (MACE). Another systematic review by Palmer et al. (2021) in The Lancet Diabetes & Endocrinology reinforced these results, noting that combination therapy could provide complementary benefits. Meanwhile, a 2022 Cochrane review confirmed the safety profile of both drug classes but highlighted gastrointestinal side effects with GLP-1 receptor agonists and genital infections with SGLT-2 inhibitors. Overall, the consensus from these studies supports individualized treatment decisions based on patient profiles, with SGLT-2 inhibitors preferred for heart failure or kidney disease patients, and GLP-1 receptor agonists for those at high stroke or atherosclerotic risk.

Journal Reference

Zaccardi F, Khan H, Schmidt AF, et al. Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists for treatment of type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. BMJ. 2020;372:m4573. doi:10.1136/bmj.m4573.

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