Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes.

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.

Effects of intensive glucose lowering in treatment of type 2 diabetes mellitus on cardiovascular outcomes: A meta-analysis of data from 58,160 patients in 13 randomized controlled trials.

BACKGROUND: Previous trials indicated that intensive glucose lowering in treatment of patients with type 2 diabetes mellitus (T2DM) was associated with a higher incidence of mortality. We therefore conducted a meta-analysis to evaluate the benefits and harms of intensive glucose lowering therapy in treatment of T2DM patients on major cardiovascular outcomes. METHODS: Randomized controlled trials (RCTs) were obtained from searches of PubMed, EmBase, and the Cochrane Library electronic databases until Feb. 2016. Relative risk (RR) was used to measure the treatment effect by random-effect model. Meta-regression, sensitivity analyses, subgroup analyses, and publication biases were also conducted. RESULTS: Thirteen RCTs were included with 58,160 T2DM patients and reported 5719 major cardiovascular events (MACEs), 6569 deaths, 2057 cardiac death cases, 3201 myocardial infarction (MI) cases, 1835 stroke cases, and 1778 congestive heart failure cases. Intensive glucose lowering therapy significantly reduced risk of MACEs (RR: 0.92; 95%CI: 0.85-1.00; P=0.042), and MI (RR: 0.90; 95%CI: 0.82-0.98; P=0.020) compared with conventional glucose control therapy. Furthermore, intensive glucose lowering therapy has no significant effect on the incidence of total mortality (RR: 0.98; 95%CI: 0.91-1.07; P=0.693), cardiac death (RR: 1.00; 95%CI: 0.87-1.04; P=0.999), stroke (RR: 0.94; 95%CI: 0.84-1.06; P=0.333), and congestive heart failure (RR: 1.19; 95%CI: 0.96-1.48; P=0.108). CONCLUSION: T2DM patients who received intensive glucose lowering therapy are associated with a reduced risk of MACEs and MI, whereas it has no significant effect on the risk of total mortality, cardiac death, stroke, and congestive heart failure. These effects might differ when stratified by baseline characteristics in T2DM patients.