SAN FRANCISCO — Adding an injection of pramlintide at mealtime to basal insulin therapy worked as well as mealtime rapid-acting insulin to control postprandial glucose levels, but caused less weight gain and hypoglycemia, a study of 112 patients with type 2 diabetes found.
The randomized, open-label, 6-month trial showed that 30% of 56 patients in the pramlintide group and 11% of 56 patients in the rapid-acting insulin group achieved the primary composite end point of a hemoglobin A1c (HbA1c) level of 7% or lower, no increase in body weight, and no severe hypoglycemia. The difference was significant, Dr. Matthew Riddle of the Oregon Health and Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.
Pramlintide is a synthetic analogue of the hormone amylin, with similar glucoregulatory properties. It is approved as adjunctive therapy for patients with type 1 or type 2 diabetes who use mealtime insulin and have not achieved good glucose control despite optimal insulin therapy, with or without oral medications. It is not approved as an alternative to mealtime insulin, said Dr. Riddle, who is an adviser and consultant for Amylin Pharmaceuticals Inc., which markets pramlintide and funded the study.
A prior study by Dr. Riddle and his associates suggested patients with type 2 diabetes on basal insulin glargine could get good postprandial glucose control and cut HbA1c levels by adding mealtime pramlintide without prandial insulin, and without weight gain (Diabetes Care 2007;30:2794-9).
The current study enrolled adults with type 2 diabetes who had baseline HbA1c levels of 7%–10%, were on any combination of oral diabetes medications (metformin, sulfonylureas, or thiazolidinediones), and who were not taking insulin or had used insulin for no more than 6 months at doses of less than 50 U/day.
Both groups started basal insulin (glargine or detemir) on day 1 and titrated as needed, with a fasting plasma glucose goal of 70–100 mg/dL. The pramlintide group started pramlintide (120 mcg before major meals) on day 1 and could titrate down to 60 mcg if needed because of nausea. The rapid-acting insulin group used basal insulin alone for 4 weeks to decrease the risk of insulin-induced hypoglycemia, then added rapid-acting insulin (5 U with major meals).
By week 24, a baseline average HbA1c level of 8.3% in each group had decreased by 0.9% in the pramlintide group and by 1.1% with rapid-acting insulin. In the pramlintide group, 45% of patients reached an HbA1c level of less than 7%, and 29% reached levels below 6.5%, compared with 55% and 32%, respectively, in the rapid-acting insulin group. The differences were not statistically significant in the intent-to-treat analyses.
After 6 months, patients in the rapid-acting insulin group gained an average of 4.2 kg, compared with 0.3 kg in the pramlintide group. Hypoglycemia was seen in 55% of the pramlintide group and 82% of the rapid-acting insulin group. Nausea affected 21% of pramlintide patients and none in the prandial insulin group. Two patients stopped pramlintide because of nausea.
Dr. Riddle also has been an adviser and consultant and has received research support from Eli Lilly & Co., Novo Nordisk Inc., and Sanofi-Aventis, which also make insulin and oral glucose control agents.