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Aim: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose‐lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. Materials and Methods: In this systematic review and meta‐analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study‐specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta‐regression was employed to analyse the relationships between outcomes and HbA1c reduction. Results: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non‐fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75‐0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92‐1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78‐0.93), nephropathy (HR 0.71; 0.58‐0.87) and composite microvascular outcomes (HR 0.88; 0.77‐1.00). Meta‐regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non‐fatal MI, stroke and retinopathy, but these were not statistically significant. Conclusions: In people with T2D, intensive glucose control was associated with a reduced risk of non‐fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose‐lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Despite global recommendations for type 2 diabetes mellitus treatment to maintain optimal glycaemic targets, a significant proportion of people remain in suboptimal glycaemic control. Our objective was to investigate the impact of intensification delay after basal insulin (BI) initiation on long‐term complications in people with suboptimal glycaemia. Materials and Methods: We conducted a retrospective cohort study in individuals with type 2 diabetes mellitus initiated on BI. Those with suboptimal glycaemia (glycated haemoglobin ≥7% or ≥53 mmol/mol) within 12 months of BI initiation were divided into early (treatment intensified within 5 years), or late (≥5 years) intensification groups. We estimated the age‐stratified risks of micro‐ and macrovascular complications among these groups compared with those with optimal glycaemia (glycated haemoglobin <7%). Results: Of the 13 916 people with suboptimal glycaemia, 52.5% (n = 7304) did not receive any treatment intensification. In those aged <65 years, compared with the optimal glycaemia group late intensification was associated with a 56% higher risk of macrovascular complications (adjusted hazard ratio 1.56; 95% confidence intervals 1.08, 2.26). In elderly people (≥65 years), late intensification was associated with a higher risk of cardiovascular‐related death (1.62; 1.03, 2.54) and a lower risk of microvascular complications (0.26; 0.08, 0.83). Conclusions: Those who had late intensification were at an increased risk of cardiovascular death if they were ≥65 years and an increased risk of macrovascular complications if they were <65 years. These findings highlight the critical need for earlier intensification of treatment and adopting personalized treatment strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]