Search

Aim: To evaluate the efficacy and safety of the initial combination therapy versus a stepwise approach in newly diagnosed type 2 diabetes (T2D) by conducting a systematic review and meta‐analysis of observational cohort studies and randomized controlled trials (RCTs). Methods: Studies were identified from MEDLINE, Embase, the Cochrane Library, and through search of bibliographies to January 2022. Study‐specific risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Eight articles including four unique RCTs (n = 5527 participants) and one observational cohort study (n = 200) that compared initial combination therapy versus stepwise therapy were included. The RR for myocardial infarction comparing initial combination therapy versus stepwise therapy was 1.21 (95% CI 0.74‐2.00). Initial combination therapy reduced levels of fasting plasma glucose and glycated haemoglobin: mean differences −0.97 mmol/L (95% CI −1.41, −0.53) and −24.92 mmol/mol (95% CI −25.67, −24.27), respectively. Initial combination therapy versus stepwise therapy reduced lipid levels, blood pressure and intima media thickness, with no differences in body composition variables, neuropathy, retinopathy or adverse events. Single‐study results showed that initial combination therapy reduced creatinine levels and urine albumin excretion rate. The quality of the evidence ranged from moderate to very low. Conclusions: Except for improving cardiometabolic and glycaemic variables, a limited number of studies characterized by small sample sizes show that initial combination therapy for newly diagnosed T2D may be similar in efficacy and safety to stepwise therapy with respect to cardio‐renal outcomes. There is a lack of sufficient evidence to recommend initial combination therapy with glucose‐lowering agents in newly diagnosed T2D with the aim of preventing cardio‐renal outcomes. Definitive RCTs are warranted. [ABSTRACT FROM AUTHOR]

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]