Effects of 4 weeks' administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations

The effects of 4 weeks' administration of pramlintide an analogue of the human hormone amylin, on blood glucose control in 215 patients with insulin-dependent diabetes mellitus were examined in a 4-week, randomized, double-blind, placebo-controlled, parallel-group trial. Pramlintide was administered subcutaneously prior to meals in four dosing regimens: 30 mu g four times per day (breakfast, lunch, dinner, and evening snack), 30 mu g three times per day (breakfast, lunch and dinner [BLD]), 30 mu g three times per day (breakfast, dinner and evening snack [BDS]), and 60 mu g twice per day (breakfast and dinner). After 4 weeks of pramlintide 30 mu g four times per day administration, there was a statistically significant reduction in the mean 24 h plasma glucose concentration when compared to placebo (-1.4 +/- 0.5 vs 0.3 +/- 0.5 mu mol/l, p = 0.009). Serum fructosamine concentrations were reduced 62 +/- 10 mu mol/l in the pramlintide 30 mg four times per day group, 43 +/- 7 mu mol/l in the pramlintide 30 mu g three times gel-day (BLD) group, 47 +/- 6 mu mol/l in the pramlintide 30 mu g three times per day (BDS) group, 46 +/- 7 mu mol/l in the pramlintide 60 mu g twice per day group, and 29 +/- 8 mu mol/l by placebo. The incidence of hypoglycaemia was not different in any pramlintide group compared to the placebo group. Nausea, the most frequent adverse event, subsided after the first week of treatment in the majority of patients. In conclusion, pramlintide improved blood glucose control over a 4-week period without increased hypoglycaemia and was well tolerated. Future studies using a longer period of pramlintide administration with assessment of HbA(1c) as the measurement of glycaemic control are warranted.