Risk–Benefit Trade-offs of GLP-1RAs and SGLT-2is in Type 2 Diabetes Mellitus (T2D): Systematic Review, Meta-Analysis, and Net Benefit Modeling

Nov 7, 2025Diabetes therapy : research, treatment and education of diabetes and related disorders

Balancing Risks and Benefits of Two Diabetes Drug Types in Type 2 Diabetes: Review and Analysis

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Abstract

In a meta-analysis of 17 cardiovascular outcome trials involving 132,038 participants, both GLP-1 receptor agonists and SGLT-2 inhibitors reduced .

  • Both GLP-1 receptor agonists and SGLT-2 inhibitors demonstrated a reduction in major adverse cardiovascular events with hazard ratios of 0.87.
  • SGLT-2 inhibitors were superior to GLP-1 receptor agonists in reducing and renal outcomes.
  • GLP-1 receptor agonists were associated with an increased risk of retinopathy, while SGLT-2 inhibitors were linked to a higher incidence of genitourinary infections and diabetic ketoacidosis.
  • Net benefits favored GLP-1 receptor agonists for major adverse cardiovascular events, while SGLT-2 inhibitors showed marginal net benefits depending on the harms considered.
  • The certainty of evidence was rated high for efficacy outcomes and moderate for safety concerns.

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Key numbers

HR 0.87
Reduction with GLP-1RAs
Pooled hazard ratio for across trials.
HR 0.69
Heart Failure Hospitalization with SGLT-2is
Pooled hazard ratio for .
+2.5/1000
Net Benefit of GLP-1RAs for
Net benefit per 1000 treated patients.

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