Basal insulin plus pramlintide at mealtime controls glucose, with lower hypoglycemia risk

June 9, 2008

Pramlintide injection added to basal insulin at mealtime is similar to titrated rapid-acting insulin in achieving glycemic control but with a lower risk of hypoglycemia and no weight gain in patients with type 2 diabetes, said Matthew Riddle, MD, head, section of diabetes, division of endocrinology/diabetes/clinical nutrition, Oregon Health and Sciences University, Portland.

Pramlintide injection added to basal insulin at mealtime is similar to titrated rapid-acting insulin in achieving glycemic control but with a lower risk of hypoglycemia and no weight gain in patients with type 2 diabetes, said Matthew Riddle, MD, head, section of diabetes, division of endocrinology/diabetes/clinical nutrition, Oregon Health and Sciences University, Portland.

"Beginning mealtime treatment with pramlintide could be a preferable potential alternative to rapid-acting insulin for many patients," he said.

The two strategies were compared in an open-label, 24-week, multicenter study of 112 patients who were either insulin-naive or taking less than 50 units of daily of insulin for less than 6 months. To be included, patients had to have a hemoglobin A1c of 7 to 10% and could be taking any combination of metformin, a sulfonylurea, and a thiazolidinedione.

The mean body mass index at baseline was 36 kg/m2. Almost half the patients had used insulin previously.

Basal insulin was titrated in both groups to achieve a fasting plasma glucose levels of 70 to <100 mg/dL. A fixed 120-mcg dose of pramlintide was started on day 1; in the other treatment group, rapid-acting insulin was started at week 4 to allow titration of the initial basal insulin dose to reduce the risk of mealtime insulin-induced hypoglycemia.

At 24 weeks, the reductions in A1c levels from baseline were similar with the two strategies (0.9% in the pramlintide-treated patients versus 1.1% in the group receiving rapid-acting insulin). Final fasting plasma glucose levels were also similar in the pramlintide and rapid-acting insulin groups (122 mg/dL vs. 123 mg/dL, respectively).

Patients treated with rapid-acting insulin gained a mean of 6.2 kg of body weight whereas those treated with pramlintide had a reduction in body weight of 0.3 kg (p < 0.0001 versus rapid-acting insulin).

Fifty-five percent of the pramlintide group experienced a hypoglycemic episode compared with 82% of those treated with rapid-acting insulin; there were no severe hypoglycemic events reported.

The primary composite endpoint of an A1c level ≤7.0% with no increase in body weight and no severe hypoglycemia was achieved by 30% of pramlintide recipients versus 11% of patients taking rapid-acting insulin (p < 0.05).

Twenty-one percent of patients in the pramlintide group had nausea compared with 0% of the group taking rapid-acting insulin. Nausea in the pramlintide group was mostly mild to moderate in severity; only one case was reported during the last 6 weeks of the study. There were two subjects in the pramlintide group who dropped out of the study because of nausea. The total dropout rates were 14% in the pramlintide group and 11% in the group taking rapid-acting insulin.