Insulin glargine as effective as lispro in controlling HbA1c

In patients with type 2 diabetes, basal and prandial insulin analogue are equally effective additions to therapeutic regimens to lower HbA1c levels.

To determine which form of insulin is superior, researchers from Germany and the United Kingdom randomly assigned 418 patients with type 2 diabetes mellitus on oral hypoglycemic agents to once-daily insulin glargine (n=205) or thrice-daily insulin lispro (n=210). The investigation, conducted in 69 sites across Australia and Europe, lasted 44 weeks.

The predefined limit for non-inferiority (0.4%) was maintained with both forms of insulin; in the glargine group, mean HbA1c decrease was –1.7% (from 8.7% to 7.0%) and in the lispro group, –1.9% (from 8.7% to 6.8%). One-hundred and six patients (57%) in the glargine group and 131 in the lispro group (69%) achieved an HbA1c level of 7% or less.

The decrease in both mean fasting blood glucose (P<.0001) and nocturnal blood glucose (P=.0041) were better in the glargine group, though lispro was superior in controlling postprandial blood glucose throughout the day (P<.0001). Patients in the glargine group had fewer hypoglycemic events and reported greater satisfaction than those in the lispro group. – by Stacey L. Adams

Lancet. 2008;371:1073-1084.

This study is fascinating and shows the importance of focusing on the details of a clinical treatment protocol in order to understand what is being shown. This study should be compared with the 4T study of metformin/sulfonylurea-treated patients given insulin detemir once or twice daily vs. insulin aspart before each meal. In that study, HbA1c fell from 8.4 to 7.6 vs. from 8.6 to 7.3, with a much more complex insulin dosing schedule and less frequent titration, but with two vs. 12 hypoglycemic events per patient per year, and weight gain 5.7 vs. 1.9 kg (N Engl J Med. 2007;357:1716-30.).

It appears that there is a trade-off — more related to the titration scheme than to the precise long-acting or short-acting preparation used — of better glycemic control, the positive effect vs. negative effects of what would generally be considered intolerably frequent hypoglycemia and at least a worrisome amount of weight gain. Given the recent findings of the ACCORD trial that such efforts at very aggressive glycemic control may be associated with adverse effect on mortality, it appears that the paradigm once considered optimal use of metformin, a sulfonylurea and insulin treated to almost normal levels of glycemia is not advisable for widespread use. Regimens using less aggressive titration but resulting in lesser degrees of weight gain and hypoglycemia appear preferable.

– Zachary T. Bloomgarden, MD

Endocrine Today Editorial Board member