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

Feb 21, 2024Diabetes, obesity & metabolism

Blood sugar control and large and small blood vessel problems in type 2 diabetes linked to new glucose-lowering drugs

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

169,513 participants with type 2 diabetes were included in the analysis of cardiovascular outcome trials.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with reduced risks of major adverse cardiovascular events compared to placebo, with hazard ratios of 0.88 and 0.85, respectively.
Dipeptidyl peptidase-4 inhibitors (DPP-4is) showed no significant benefits in reducing macrovascular risk.
SGLT-2is and GLP-1RAs consistently reduce the risk of macrovascular and microvascular complications, particularly kidney events.
An inverse linear relationship may exist between reductions in glycated hemoglobin (HbA1c) and risk of major adverse cardiovascular events, particularly for non-fatal stroke.
Non-significant inverse linear relationships were observed between HbA1c reduction and several vascular outcomes.

AI simplified

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; R = 14.2%), which was driven by the component of non-fatal stroke (R = 100.0%; p = .094). There were non-significant inverse linear relationships between HbA1c reduction and the risk of several vascular outcomes. 2 2

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.

Full Text

Full text is available at the source.

View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief