SAN FRANCISCO — Basal or mealtime insulin worked equally well to treat patients with type 2 diabetes after a myocardial infarction, but the mealtime group needed more insulin in a randomized, open-label study of 1,112 patients.
Previous epidemiological studies have shown an association between postprandial hyperglycemia and acute MI or death in people with diabetes. Every 1-mmol/L decrease in postprandial hyperglycemia after glucose challenge was thought to be associated with a 9% reduction in risk for MI or death in patients with diabetes.
Postprandial glucose levels in the current study were significantly higher in patients who used basal insulin therapy than in those on prandial insulin therapy, but there was no significant difference between groups in the primary end point of cardiovascular outcomes including cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for acute coronary syndromes, Dr. Itamar Raz and his associates reported.
The planned 3-year study was stopped early because of the lack of difference after a mean of 2.6 years. In the basal insulin group, 32% of patients had at least one cardiovascular event, compared with 31% in the prandial insulin group, he said at the annual scientific sessions of the American Diabetes Association.
Hemoglobin A1c (HbA1c) levels ended up being similar between groups, according to a preliminary intent-to-treat analysis of data from the HEART2D (Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Type 2 Diabetes Mellitus) trial.
Approximately half of patients in each group reached group-specific blood glucose targets, but patients in the prandial insulin group needed more insulin to reach them, said Dr. Raz of the Hadassah University Medical Center, Jerusalem.
Insulin-naive patients were randomized within 21 days of an acute MI to diabetes therapy with either prandial insulin (lispro t.i.d.) or basal insulin (twice-daily NPH insulin or once-daily glargine). The prandial group aimed for a 2-hour postprandial glucose level less than 7.5 mmol/L, and the basal group target was a fasting and plasma blood glucose level less than 6.7 mmol/L.
Both groups aimed for an HbA1c level below 7%, and rescue therapy was started if the HbA1c level was higher than 8% on two consecutive visits. For rescue, the prandial group added bedtime NPH, and the basal group converted to 70% human insulin isophane suspensions with 30% human insulin injection (Humulin 70–30).
Eli Lilly & Co., which makes insulin lispro and Humulin 70–30, sponsored the study, and some of Dr. Raz's coinvestigators were Lilly employees. Dr. Raz has been an adviser or consultant to Sanofi-Aventis, which makes insulin glargine, and to other companies including Merck & Co., the American Type Culture Collection, Keryx Biopharmaceuticals Inc., Johnson & Johnson, Pfizer Inc., and Oramed Pharmaceuticals.
Concomitant cardiovascular medications were used by 95% of patients in each group.
Patients had a mean age of 61 years, and just over a third in each group were older than 65 years. All had diabetes for at least 3 months at enrollment, no clinical signs of heart failure, and a left ventricular ejection fraction of 30% or greater.
There were 51 deaths in each group during the trial, mainly because of cardiovascular causes. Stroke killed 3 patients in the prandial insulin group and 2 in the basal group, and cardiovascular events killed 44 patients in the prandial group and 42 in the basal group.