Improvement of glycemic control in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials

Aim: Different guidelines provide similar, but not identical, therapeutic targets for HbA1c in type 2 diabetes. These targets can also depend from the different pharmacological strategies adopted for intensifying glycemic control. Data synthesis: This meta-analysis includes randomized trials adopting any pharmacological regimen for intensifying glycemic control in T2DM (versus standard of care/placebo), with a trial duration ≥2 years and a between-group HbA1c difference≥0.5%. The primary outcome was to assess the effects of the improvement of glycemic control on major cardiovascular events (MACE), ocular and renal complications, and severe hypoglycemia. Mantel-Haenszel odds ratios (MH–OR) with 95% Confidence Intervals were calculated for all the outcomes considered. We included 13 trials fulfilling the inclusion criteria. The improvement of glycemic control was associated with a lower risk of MACE (MH–OR:0.89 [95%CI 0.85–0.94]) and renal adverse events (MH–OR 0.73 [0.65–0.82]), but not all-cause mortality (MH–OR 0.95 [0.88–1.01]) and ocular adverse complications (MH–OR 0.94 [0.72–1.22]). For glucose-lowering drugs inducing hypoglycemia, a protective effect on the risk of microvascular complications, but not of MACE and all-cause mortality, was observed only for HbA1c ≤ 48 mmol/mol, but with higher risk of severe hypoglycaemia (MH–OR 2.72 [1.79–4.13]). Drugs not inducing hypoglycaemia were associated with a reduction of MACE, renal adverse events, and all-cause mortality, for HbA1c< 7% (no data for lower targets). Conclusions: The present meta-analysis show that the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular and renal complications, and all-cause mortality.