Less Nocturnal Hypoglycemia and Better Post - Dinner Glucose Control With Bedtime Insulin Glargine Compared With Bedtime NPH Insulin During Insulin

DIABETES CARE, VOLUME 23, NUMBER 8, AUGUST 2000 Previous controlled trials comparing various insulin regimens in patients with type 2 diabetes poorly controlled with oral agents have shown that the simple addition of NPH insulin at bedtime (1–3) or of 70/30 premixed insulin (70% NPH insulin/ 30% regular insulin) before supper (4) to previous treatment with sulfonylureas alone (3,2), sulfonylureas and metformin (1,3,5), or metformin alone (3) gives as good overall glycemic control than the use of several insulin injections (1,3,4,6,7). However, use of NPH insulin creates 2 problems. If NPH insulin is injected at bedtime in patients with type 2 diabetes, the greatest decrease in blood glucose is observed during the early morning hours, which is consistent with a peak in the action profile of NPH (1). This peak increases the frequency of nocturnal hypoglycemia and prevents adequate titration of the insulin dose, particularly when NPH is combined with glyburide (3). The other recognized problem with NPH is that its duration of action is too short to adequately control glucose around dinner time after an injection at bedtime the previous day (1). Another currently available basal insulin formulation is the once-daily longacting crystalline human zinc insulin. However, one injection of long-acting insulin per day seems inferior to twice-daily NPH with respect to the rate of hypoglycemia, glycemic control, and treatment satisfaction (8). Also, the variability of absorption from subcutaneous tissue is high with long-acting crystalline human zinc insulin (9). Insulin glargine is a human insulin analog produced with recombinant DNA technology with the addition of 2 basic amino acids (arginine) to the B-chain and a substitution of asparagine with glycine in position A21 in the insulin molecule. These changes result in a shift of the isoelectric point from 5.4 in native insulin toward a pH of 7.0 in insulin glargine. As a result, insulin glargine precipitates at physiological pH in subcutaneous tissue after injection, which delays its absorption. Addition of zinc to stabilize interhexamer contacts further prolongs the activity of this analog. Studies in healthy volunteers have indicated that insulin glargine indeed has a smooth peakless profile of action that is required from a basal insulin injected once daily (10). However, the possible clinical benefits of insulin glargine compared with other currently From the Department of Medicine (H.Y.-J.), Division of Diabetes, University of Helsinki, Helsinki, Finland; and Hoechst Marion Roussel Deutschland Clinical Development (A.D., M.Z.), Frankfurt, Germany. Address correspondence and reprint requests to Hannele Yki-Järvinen, MD, University of Helsinki, Department of Medicine, Division of Diabetes, Haartmaninkatu 4, P.O. Box 340, 00029 HUCH, Helsinki, Finland. E-mail: [email protected]. Received for publication 3 March 2000 and accepted in revised form 27 April 2000. H.Y.-J. is a member on an advisory panel for and has received honoraria for speaking engagements from Aventis Pharmaceuticals. A.D. and M.Z. are employed by Aventis Pharmaceuticals. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; DCCT, Diabetes Control and Complications Trial; FBG, fasting blood glucose. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Less Nocturnal Hypoglycemia and Better Post-Dinner Glucose Control With Bedtime Insulin Glargine Compared With Bedtime NPH Insulin During Insulin Combination Therapy in Type 2 Diabetes O R I G I N A L A R T I C L E