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Diabetes Obesity Metabolism - 2024 - Kunutsor - Glycaemic control and macrovascular and microvascular outcomes in type 2 (1).pdf (1.12 MB)

Glycaemic control and macrovascular and microvascular outcomes in type 2 diabetes: Systematic review and meta-analysis of cardiovascular outcome trials of novel glucose-lowering agents.

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posted on 2024-03-04, 12:47 authored by Setor K Kunutsor, Francesco Zaccardi, Victoria G Balasubramanian, Clare L Gillies, Vanita R Aroda, Samuel SeiduSamuel Seidu, Melanie J Davies, Kamlesh Khunti

Aim

Using a systematic review and meta-analysis of placebo-controlled cardiovascular outcome trials (CVOTs) of newer glucose-lowering agents [sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is)] in type 2 diabetes (T2D), we aimed to determine the macrovascular and microvascular outcomes of these agents and clarify the relationships between glycated haemoglobin (HbA1c) reduction and risk of these outcomes.

Materials and methods

Randomized controlled trials were identified from MEDLINE, Embase and the Cochrane Library until September 2023. Study-specific hazard ratios with 95% confidence intervals (CIs) were pooled, and meta-regression was used to assess the relationships between outcomes and between trial arm HbA1c reductions.

Results

Twenty unique CVOTs (six SGLT-2is, nine GLP-1RAs, five DPP-4is), based on 169 513 participants with T2D, were eligible. Comparing SGLT-2is, GLP-1RAs and DPP-4is with placebo, the hazard ratios (95% CIs) for 3-point major adverse cardiovascular events were 0.88 (0.82-0.94), 0.85 (0.79-0.92) and 1.00 (0.94-1.06), respectively. SGLT-2is and GLP-1RAs consistently reduced the risk of several macrovascular and microvascular complications, particularly kidney events. DPP-4is showed no macrovascular benefits. There was potential evidence of an inverse linear relationship between HbA1c reduction and 3-point major adverse cardiovascular event risk (estimated risk per 1% reduction in HbA1c: 0.84, 95% CI 0.67-1.06; p = .14; R2  = 14.2%), which was driven by the component of non-fatal stroke (R2  = 100.0%; p = .094). There were non-significant inverse linear relationships between HbA1c reduction and the risk of several vascular outcomes.

Conclusions

SGLT-2is and GLP-1RAs showed consistent risk reductions in macrovascular and microvascular outcomes. The vascular benefits of SGLT-2is and GLP-1RAs in patients with T2D extend beyond mere glycaemic control.

Funding

NIHR Leicester Biomedical Research Centre

Servier Affaires Medicales (Paris, France)

History

Author affiliation

College of Life Sciences/Population Health Sciences

Version

  • VoR (Version of Record)

Published in

Diabetes, obesity & metabolism

Publisher

John Wiley & Sons Ltd

issn

1462-8902

eissn

1463-1326

Copyright date

2024

Available date

2024-03-04

Spatial coverage

England

Language

eng

Deposited by

Dr Setor Kunutsor

Deposit date

2024-03-01

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