- •Drugs not inducing hypoglycemia were associated with a lower risk of MACE and renal complications and all-cause mortality.
- •Drugs inducing hypoglycemia was associated with lower risk of complications, but higher risk of severe hypoglycemia.
- •The reduction of ocular adverse events was observed only for HbA1c ≤ 6.5% in the intensive treatment arm.
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.
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).
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.
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Published online: May 22, 2021
Accepted: May 13, 2021
Received in revised form: May 11, 2021
Received: February 25, 2021Handling Editor: A. Giaccari
© 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.