Aggressive glucose control may not improve micro-, macrovascular outcomes in type 2 diabetes

Aggressive glucose control strategies yielded mixed results for microvascular complications and did not appear to affect myocardial infarction (MI) rates in a new cohort study that followed patients over four years.

Researchers studied adults with type 2 diabetes who had hemoglobin A1c (HbA1c) values less than 7% while taking two or more oral agents or basal insulin, followed by at least one HbA1c value of 7% to 8.5%. Patients were followed beginning on the date of the first HbA1c value of ≥7% until a clinical event, death, or disenrollment occurred or until the end of the study. The study defined glucose control strategies as first intensification of glucose-lowering therapy at HbA1c levels of ≥7%, ≥7.5%, ≥8%, or ≥8.5%. Study end points were acute MI, onset or progression of albuminuria, and progression or lack of progression to worse renal function based on estimated glomerular filtration rate (GFR). The study results were published online July 22 by Diabetes Care.

Of 58,671 patients, 1,655 (2.82%) had an acute MI during follow-up. Acute MI rates did not appear to differ according to treatment intensification strategy, although a trend was seen toward fewer acute MIs with treatment intensification at an HbA1c of ≥7% compared with ≥8.5% (P=0.08) and ≥8% compared with ≥8.5% (P=0.05). Of 57,927 patients in the kidney function analysis, 25,930 (44.76%) had a decrease in estimated GFR. Decreased renal function was significantly more common in patients who received treatment intensification at an HbA1c of ≥7% compared with ≥8% (P=0.04) or ≥8.5% (P=0.03), but not compared with ≥7.5% (P=0.18).

Of 51,179 patients in the albuminuria analysis, 12,085 (23.61%) had onset or progression of albuminuria. Albuminuria onset or progression was less likely in patients who received treatment intensification at an HbA1c of ≥7% (P=0.02), ≥7.5% (P=0.04), and ≥8% (P=0.01) compared with ≥8.5%, but no advantages were seen when comparing intensification at ≥7% with ≥7.5% (P=0.35), ≥7.5% with ≥8% (P=0.73), or ≥7% with ≥8% (P=0.27).

The authors noted that longer follow-up could have modified their results and that they were unable to model mortality as an outcome, among other limitations. However, they concluded that their results confirm those of larger trials, such as ACCORD and ADVANCE, in a broader range of patients. “In a large representative cohort of adults with type 2 diabetes, more aggressive glucose-control strategies have mixed short-term effects on microvascular complications and do not reduce the myocardial infarction rate over 4 years of follow-up,” they wrote. They called for larger trials to confirm their results over longer periods.