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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]

Aims: To compare the effectiveness and safety of gliclazide modified release (MR) to sitagliptin as type 2 diabetes mellitus (T2D) treatments in a real‐world patient population. Materials and Methods: This retrospective cohort study used records from the UK Clinical Practice Research Datalink. The cohort consisted of adult patients with T2D newly treated with either gliclazide MR or sitagliptin as second‐line treatment added to metformin and with a glycated haemoglobin (HbA1c) level of ≥7.0% (53 mmol/mol). Patients were 1:1 matched using high‐dimensional propensity score matching and followed to determine the time taken to reach an HbA1c <7.0%. Secondary outcomes included time to HbA1c ≤6.5% (48 mmol/mol), time to ≥1% (11 mmol/mol) HbA1c reduction from baseline, treatment persistence and durability, and hypoglycaemic events. Results: Among the 1986 patients included, those on gliclazide MR more likely achieved an HbA1c <7.0% [hazard ratio (HR): 1.35; 95% confidence interval (CI): 1.15‐1.57], HbA1c ≤6.5% (HR: 1.51; 95% CI: 1.19‐1.92) or had an HbA1c reduction ≥1% from baseline (HR: 1.11; 95% CI: 1.00‐1.24) compared with patients on sitagliptin. Durability (log‐rank P =.135) and persistence (P =.119) were similar between the two groups. Hypoglycaemic events were uncommon (23 total severe and non‐severe events; incidence rate, 3.7 per 1000 patient years), with 4.7 and 2.6 events per 1000 patient years with gliclazide MR and sitagliptin treatment, respectively. Conclusions: In this real‐world study, second‐line gliclazide MR was more effective than sitagliptin in reducing HbA1c, with similar durability and persistence and low rates of hypoglycaemic events, in individuals with T2D on metformin treatment and HbA1c above the target of 7.0%. [ABSTRACT FROM AUTHOR]

Aims: Hypoglycaemia is associated with increased cardiovascular risk among individuals with diabetes mellitus. It has been hypothesized that hypoglycaemia may trigger autonomic changes leading to increased cardiac arrhythmia risk. We conducted a systematic review and meta‐analysis to explore this association. Materials and methods: Ovid Medline, Embase, Scopus, Web of Science and Cochrane were searched from inception to October 10, 2017. We included studies of adults with diabetes (Type 1 or Type 2) that compared acute electrocardiogram (ECG) changes during episodes of hypoglycaemia and euglycaemia. Results: Our search resulted in 4625 citations, among which 20 studies met the predefined inclusion criteria. Finally, 12 studies were included in the descriptive analysis and 15 in the meta‐analysis. Overall hypoglycaemia was associated with a reduction in heart rate variability and an increase in arrhythmia occurrence. QTc interval length was more significantly prolonged during hypoglycaemia compared to euglycaemia (pooled mean difference [95% confidence intervals] [0.64 (0.27‐1.01], P = ·001). Subgroup analysis based on diabetes type showed that QTc prolongation occurred in individuals with Type 1 and Type 2 diabetes; however, the change between euglycaemia reached statistical significance only among individuals with Type 1 diabetes. Conclusion: Our findings suggest that hypoglycaemia results in ECG alterations that are associated with increased risk of cardiac arrhythmia, which is associated with increased cardiovascular events and mortality. More clinical studies are needed to determine the cardiac risks of hypoglycaemia in individuals with diabetes, especially in Type 2 diabetes. [ABSTRACT FROM AUTHOR]