Article type
Year
Abstract
Background: Type 2 diabetes (T2D) therapies other than metformin have had a little obvious favorable effect on cardiovascular outcomes until recently. This may reflect the influence of hypoglycemia.
Objectives: To update the summarized effects of blood glucose control with antihyperglycaemic agents with minimal hypoglycaemia risk on cardiovascular outcomes in patients with T2D.
Methods: We updated the meta-regression analysis by including more randomized controlled trials (RCTs) comparing the relative efficacy and safety of antidiabetic drugs with less hypoglycaemia risk, which were comprehensively researched in MEDLINE, Embase and the Cochrane Library up to Mar 16, 2020. We used mixed-effects meta-regression analysis to investigate whether the relationship between haemoglobin A1c (HbA1c) reduction and the risk of major adverse cardiovascular events (MACE), myocardial infarction, stroke, cardiovascular death, all-cause death, and hospitalization for heart failure is consistent with our previous study conclusion.
Results: After including additional 6 RCTs, a total of 16 trials comprising 143288 participants with T2D were included and provided information on 14574 MACE during a median follow-up of 2.3 years. The mean HbA1c concentration was 0.44% lower (range, 0.27%-0.86%) for participants given antihyperglycaemic agents than those given placebo. The meta-regression analysis demonstrated that HbA1c reduction was significantly associated with a decreased risk of MACE (β value for LnRR [natural logarithm of relative risk], −0.43 to −0.62; P ≤ 0.001) even after adjusting for possible confounding factors including age, sex, baseline HbA1c, duration of follow-up, difference in achieved systolic blood pressure, difference in achieved body weight, and risk difference in hypoglycaemia. Lowering HbA1c by 1% conferred a significant risk reduction of 29% (95% confidence interval, 19%-38%) for MACE. By contrast, the meta-regression analysis for trials using conventional agents failed to demonstrate a significant relationship between achieved HbA1c difference and MACE risk (P > 0.74).
Conclusions: Our updated meta-regression analysis supported our previous study conclusion that the risk reduction of MACE appears to be significantly associated with HbA1c reduction in a linear relationship, if newer T2D agents with less hypoglycaemic hazard are used.
Patient or healthcare consumer involvement: None
Objectives: To update the summarized effects of blood glucose control with antihyperglycaemic agents with minimal hypoglycaemia risk on cardiovascular outcomes in patients with T2D.
Methods: We updated the meta-regression analysis by including more randomized controlled trials (RCTs) comparing the relative efficacy and safety of antidiabetic drugs with less hypoglycaemia risk, which were comprehensively researched in MEDLINE, Embase and the Cochrane Library up to Mar 16, 2020. We used mixed-effects meta-regression analysis to investigate whether the relationship between haemoglobin A1c (HbA1c) reduction and the risk of major adverse cardiovascular events (MACE), myocardial infarction, stroke, cardiovascular death, all-cause death, and hospitalization for heart failure is consistent with our previous study conclusion.
Results: After including additional 6 RCTs, a total of 16 trials comprising 143288 participants with T2D were included and provided information on 14574 MACE during a median follow-up of 2.3 years. The mean HbA1c concentration was 0.44% lower (range, 0.27%-0.86%) for participants given antihyperglycaemic agents than those given placebo. The meta-regression analysis demonstrated that HbA1c reduction was significantly associated with a decreased risk of MACE (β value for LnRR [natural logarithm of relative risk], −0.43 to −0.62; P ≤ 0.001) even after adjusting for possible confounding factors including age, sex, baseline HbA1c, duration of follow-up, difference in achieved systolic blood pressure, difference in achieved body weight, and risk difference in hypoglycaemia. Lowering HbA1c by 1% conferred a significant risk reduction of 29% (95% confidence interval, 19%-38%) for MACE. By contrast, the meta-regression analysis for trials using conventional agents failed to demonstrate a significant relationship between achieved HbA1c difference and MACE risk (P > 0.74).
Conclusions: Our updated meta-regression analysis supported our previous study conclusion that the risk reduction of MACE appears to be significantly associated with HbA1c reduction in a linear relationship, if newer T2D agents with less hypoglycaemic hazard are used.
Patient or healthcare consumer involvement: None