Objective: The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D.

Methods: We searched Ovid MEDLINE, Embase, Cochrane, and CINHAL for randomized control trials comparing standard glucose targets to intensive glucose targets with pre-specified HbAlevels. Subgroup analysis was also performed to account for the inclusion of glucose only versus multi-factorial intervention trials. Results are reported as risk ratio (RR) and 95% confidence interval (CI).

Results: Fifty-seven publications including 19 trials were included. Compared to conventional glycemic control, intensive glycemic control decreased the risk of non-fatal myocardial infarction (0.8, 0.7-0.91), macroalbuminuria (0.72, 0.5--0.87), microalbuminuria (0.67, 0.52-0.85), major amputation (0.6, 0.38-0.96), retinopathy (0.75 ,0.63-0.9), and nephropathy (0.78, 0.63-0.97). The risk of hypoglycemia increased with intensive glycemic control than conventional treatment (2.04, 1.34-3.1). No reduction in all-cause or cardiovascular mortality was observed. However, in the context of multifactorial intervention, intensive glucose control was associated with a significant reduction in all-cause mortality (0.74, 0.57-0.95).

Conclusion: Targeting HbA levels should be individualized based on the clinical status, balancing risks and benefits and potential risk for developing these complications among people with T2D.

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