Issue 182 Item 12 Metformin Safe and Effective Combined with Single Daily Inject

Single daily dose injections of either NPH insulin, biphasic insulin aspart, or biphasic human insulin in combination with metformin are equally effective strategies for starting type 2 diabetes patients on insulin therapy.

An intermediate acting insulin, such as NPH, is often used in combination with oral agents when starting patients on insulin therapy. Single daily injections before bedtime are used to reduce endogenous glucose output during the night hours. However, many type 2 diabetes patients eat a large portion of their calories at dinner, and recent studies have suggested that biphasic insulin preparations given before dinner may also be effective in once-daily injection routines.

Investigators led by Charles Kilo, MD, of Kilo Clinical Research, Ltd, St. Louis, Missouri, Unites States, and colleagues compared the efficacy and safety of metformin used in combination with once-daily injections of either biphasic insulin aspart (NovoLog Mix 70/30), NPH insulin (Novolin N), or biphasic human insulin (Novolin 70/30).

The study included 140 insulin-naïve type 2 diabetes patients with inadequate glycemic control after at least 3 months of metformin as monotherapy or in combination with a sulphonylurea or repaglinide. After a 4-week run in period of metformin monotherapy, patients were randomized to receive metformin for 12 weeks in combination with either biphasic insulin aspart 10 minutes before dinner (n = 46; mean age, 57.2; 25 males), NPH insulin at bedtime (n = 47; mean age, 55.1; 19 males), or biphasic human insulin 30 minutes before dinner (n = 47; mean age, 55.4; 29 males).

Each of the insulin combination regimens effectively improved glycemic control, reports Dr. Kilo, and no significant differences were detected between the treatments. Glycosylated hemoglobin levels decreased by 1.3%, 1.2%, and 1.1% with biphasic insulin aspart, NPH insulin, and biphasic human insulin, respectively, and fasting plasma glucose decreased from baseline by 31%, 37%, and 28%.

Greater decreases in fasting blood glucose were associated with greater decreases in glycosylated hemoglobin levels. Among patients who achieved fasting blood glucose levels of 90-126 mg/dl, glycosylated hemoglobin decreased by 2.3% with biphasic insulin aspart (n = 9), 1.9% with NPH insulin (n = 9), and 1.8% with biphasic human insulin n = 8.

Each of the treatment regimens was well-tolerated, and no major hypoglycemic events were reported. However, subjects treated with biphasic insulin aspart or biphasic human insulin gained slightly more weight (0.7 and 1.0 kg, respectively) than those treated with NPH insulin (0.1kg).

"The results of this study indicate that patients with type 2 diabetes can safely and effectively begin insulin therapy using once-daily injections of biphasic insulin aspart, biphasic human insulin, or NPH insulin in combination with maximum recommended doses of metformin," the researchers conclude.

In addition, they suggest that, "a more intensive approach would potentially have resulted in more patients attaining target blood glucose values." J Diabetes Complications 2003 Nov-Dec;17:6:307-13