Intensive glycemic control and macrovascular, microvascular, hypoglycemia complications and mortality in older (age ?60years) or frail adults with type 2 diabetes: a systematic review and meta-analysis from randomized controlled trial and observation studies

Introduction: Guidelines for type 2 diabetes (T2D) recommend individualized HbA1c targets to take into account patient age or frailty. We synthesized evidence from randomized controlled trials and observational studies for intensive glycemic control (HbA1c target ≤58mmol/mol) versus standard care, in elderly (age ≥60years) or frail adults with T2D. Methods: Searches were performed utilizing recognized terms for T2D, frailty, older age, and HbA1c control and outcomes of interest. Meta-analysis was performed where possible. Primary outcomes included all-cause mortality, severe hypoglycemia, and hospital admission rates. Vascular complications, cognitive decline, and falls/fractures were secondary outcomes. Results: 7,528 studies were identified of which 15 different clinical studies were selected. No difference was noted in all-cause mortality with intensive control (pooled hazard ratio 0.96, 95% confidence interval 0.90–1.03), but risk of severe hypoglycemia increased (2.45, 2.22–2.72). Intensive control was associated reductions in microvascular (0.73, 0.68–0.79) and macrovascular complications (0.84, 0.79–0.89). Outcome data for risk of hospitalization, cognition, and falls/fractures were limited. Conclusion: Intensive glycemic control was associated with reduced rates of complications but increased severe hypoglycemia. Significant heterogeneity exists and the impact of different drug regimens is unclear. Caution is needed when setting glycemic targets in elderly or frail individuals