Objective: To investigate the efficacy and safety of continuous (basal-bolus) subcutaneous pramlintide infusion (CSPI) in patients with type 1 diabetes mellitus.
Methods: A 16-week, open-label, single-arm pilot study enrolled 11 patients (mean +/- SD values: age, 39.9 +/- 4.0 years; hemoglobin A1c, 8.20% +/- 0.60%; weight, 92.3 +/- 18.4 kg; body mass index, 29.7 +/- 5.1 kg/m2) with longterm type 1 diabetes mellitus (20.7 +/- 1.3 years; duration of pump therapy, 9.5 +/- 6.0 years). Pramlintide basal infusion was begun with continuous subcutaneous infusion at 9 microg/h. After 3 days, premeal bolus doses of pramlintide were initiated at 15 microg and titrated to 60 microg per meal. Basal and bolus insulin doses were reduced 10% on initiation of CSPI and adjusted thereafter as needed to prevent hypoglycemia.
Results: After 16 weeks of pramlintide therapy, mean +/- SD hemoglobin A1c decreased to 7.85% +/- 0.74% (-0.35%). The fasting glucose level declined from 198.2 +/- 66.9 mg/dL to 135.8 +/- 63.9 mg/dL. The mean weight decreased to 91.8 +/- 20.1 kg (-0.5 kg) at week 12. The daily bolus insulin requirement decreased 20%; daily basal insulin was unchanged (27.7 +/- 11.7 U). All patients experienced mild postprandial hypoglycemia, but no severe hypoglycemia was reported. Three of the 11 study participants experienced mild initial nausea, but all patients successfully titrated bolus doses to 60 microg within 3 weeks.
Conclusion: In this pilot study of 11 patients with type 1 diabetes using insulin pumps, CSPI seemed safe and well tolerated, did not alter pramlintide pharmacokinetic variables, and reduced fasting glucose levels. Larger studies of this method for pramlintide administration seem warranted.
Trial registration: ClinicalTrials.gov NCT00502138.