Effects of DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors and sulphonylureas on mortality, cardiovascular and renal outcomes in type 2 diabetes: A network meta-analyses-driven approach

Andreas Brønden*, Mikkel Bring Christensen, Dorte Glintborg, Ole Snorgaard, Allan Kofoed-Enevoldsen, Gitte Krogh Madsen, Katja Toft, Jette Kolding Kristensen, Kurt Højlund, Troels Krarup Hansen, Esben Søndergaard, Katrine Bagge Hansen*

*Corresponding author for this work

Abstract

AIMS: The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile.

METHODS: Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials.

RESULTS: SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup.

CONCLUSIONS: The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as an add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease.

Original languageEnglish
Article numbere15157
JournalDiabetic medicine : a journal of the British Diabetic Association
Volume40
Issue number8
Pages (from-to)e15157
ISSN0742-3071
DOIs
Publication statusPublished - Aug 2023

Keywords

  • Cardiovascular Diseases
  • Diabetes Mellitus, Type 2/complications
  • Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
  • Glucagon-Like Peptide-1 Receptor/agonists
  • Glucose
  • Heart Failure/drug therapy
  • Humans
  • Hypoglycemic Agents/therapeutic use
  • Metformin/therapeutic use
  • Network Meta-Analysis
  • Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
  • Sulfonylurea Compounds/therapeutic use

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