Modelling incremental benefits on complications rates when targeting lower HbA1c levels in people with Type 2 diabetes and cardiovascular disease

Aim Glucose‐lowering interventions in Type 2 diabetes mellitus have demonstrated reductions in microvascular complications and modest reductions in macrovascular complications. However, the degree to which targeting different HbA 1c reductions might reduce risk is unclear. Methods Participant‐level data for Trial Evaluating Cardiovascular Outcomes with Sitagliptin ( TECOS ) participants with established cardiovascular disease were used in a Type 2 diabetes‐specific simulation model to quantify the likely impact of different HbA 1c decrements on complication rates. Ten‐year micro‐ and macrovascular rates were estimated with HbA 1c levels fixed at 86, 75, 64, 53 and 42 mmol/mol (10%, 9%, 8%, 7% and 6%) while holding other risk factors constant at their baseline levels. Cumulative relative risk reductions for each outcome were derived for each HbA 1c decrement. Results Of 5717 participants studied, 72.0% were men and 74.2% White European, with a mean ( sd ) age of 66.2 (7.9) years, systolic blood pressure 134 (16.9) mmHg, LDL ‐cholesterol 2.3 (0.9) mmol/l, HDL ‐cholesterol 1.13 (0.3) mmol/l and median Type 2 diabetes duration 9.6 (5.1–15.6) years. Ten‐year cumulative relative risk reductions for modelled HbA 1c values of 75, 64, 53 and 42 mmol/mol, relative to 86 mmol/mol, were 4.6%, 9.3%, 15.1% and 20.2% for myocardial infarction; 6.0%, 12.8%, 19.6% and 25.8% for stroke; 14.4%, 26.6%, 37.1% and 46.4% for diabetes‐related ulcer; 21.5%, 39.0%, 52.3% and 63.1% for amputation; and 13.6%, 25.4%, 36.0% and 44.7 for single‐eye blindness. Conclusions These simulated complication rates might help inform the degree to which complications might be reduced by targeting particular HbA 1c reductions in Type 2 diabetes.