OBJECTIVE: To assess the safety and efficacy of the addition of pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: We conducted a post hoc analysis of 2 studies: a 29-week, multicenter, randomized, double-blind, placebo-controlled trial (referred to as RCT) (pramlintide, n = 82; placebo, n = 73) and an open-ended, multicenter, open-label, single-arm, observational study (referred to as clinical practice trial) (n = 150), which assessed the addition of pramlintide to CSII therapy in patients with T1DM. Pramlintide was initiated at 15 μg and titrated to 30 or 60 μg with major meals. The mealtime insulin dose was reduced by 30% to 50% at initiation, and then adjusted to optimize glycemic control. Endpoints at 29 weeks (RCT) and 6 months (clinical practice trial) included change in glycated hemoglobin (HbA1c) level, insulin dose, body weight, pre- and postprandial blood glucose level, and tolerability and safety. RESULTS: In both studies, mean baseline age was approximately 42 years, duration of diabetes was 20 to 24 years, and HbA1c level was approximately 8%. Pramlintide reduced blood glucose excursions and improved the percentage of recorded postprandial blood glucose levels < 180 mg/dL. Mean (± standard deviation) reduction in HbA1c level in the clinical practice trial was -0.3% ± 0.1% (P < 0.0001), and in the RCT was similar between pramlintide- and placebo-treated patients (-0.4% ± 0.1% and -0.3% ± 0.1%, respectively). Glycemic improvements were accomplished, with reductions in mealtime insulin doses (RCT: pramlintide, -23.8% ± 5.2%; placebo, -3.2% ± 4.1%; P < 0.0005; clinical practice trial: -27.5% ± 2.9%; P < 0.0001) and body weight (RCT: pramlintide, -2.2 kg ± 0.5 kg; placebo, +1.4 kg ± 0.3 kg; P < 0.0001; clinical practice trial: -3.2 kg ± 0.4 kg; P < 0.0001). Short-lived nausea, primarily mild to moderate in intensity, was the most common adverse event associated with pramlintide therapy. Severe hypoglycemic events occurred at a rate of 0.56 and 0.34 events per patient-year in pramlintide- and placebo-treated patients, respectively, in the RCT, and at a rate of 0.12 events per patient-year in the clinical practice trial. CONCLUSION: Addition of pramlintide to CSII therapy was safe and effective in patients with T1DM. Pramlintide should be considered for patients who are not able to optimize glycemic control with CSII therapy alone, particularly those with difficulty controlling postprandial blood glucose levels and/or body weight. TRIAL REGISTRATION: www.ClinicalTrials.gov identifiers: NCT00042458, NCT00108004.
RCT Entities:
OBJECTIVE: To assess the safety and efficacy of the addition of pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: We conducted a post hoc analysis of 2 studies: a 29-week, multicenter, randomized, double-blind, placebo-controlled trial (referred to as RCT) (pramlintide, n = 82; placebo, n = 73) and an open-ended, multicenter, open-label, single-arm, observational study (referred to as clinical practice trial) (n = 150), which assessed the addition of pramlintide to CSII therapy in patients with T1DM. Pramlintide was initiated at 15 μg and titrated to 30 or 60 μg with major meals. The mealtime insulin dose was reduced by 30% to 50% at initiation, and then adjusted to optimize glycemic control. Endpoints at 29 weeks (RCT) and 6 months (clinical practice trial) included change in glycated hemoglobin (HbA1c) level, insulin dose, body weight, pre- and postprandial blood glucose level, and tolerability and safety. RESULTS: In both studies, mean baseline age was approximately 42 years, duration of diabetes was 20 to 24 years, and HbA1c level was approximately 8%. Pramlintide reduced blood glucose excursions and improved the percentage of recorded postprandial blood glucose levels < 180 mg/dL. Mean (± standard deviation) reduction in HbA1c level in the clinical practice trial was -0.3% ± 0.1% (P < 0.0001), and in the RCT was similar between pramlintide- and placebo-treated patients (-0.4% ± 0.1% and -0.3% ± 0.1%, respectively). Glycemic improvements were accomplished, with reductions in mealtime insulin doses (RCT: pramlintide, -23.8% ± 5.2%; placebo, -3.2% ± 4.1%; P < 0.0005; clinical practice trial: -27.5% ± 2.9%; P < 0.0001) and body weight (RCT: pramlintide, -2.2 kg ± 0.5 kg; placebo, +1.4 kg ± 0.3 kg; P < 0.0001; clinical practice trial: -3.2 kg ± 0.4 kg; P < 0.0001). Short-lived nausea, primarily mild to moderate in intensity, was the most common adverse event associated with pramlintide therapy. Severe hypoglycemic events occurred at a rate of 0.56 and 0.34 events per patient-year in pramlintide- and placebo-treated patients, respectively, in the RCT, and at a rate of 0.12 events per patient-year in the clinical practice trial. CONCLUSION: Addition of pramlintide to CSII therapy was safe and effective in patients with T1DM. Pramlintide should be considered for patients who are not able to optimize glycemic control with CSII therapy alone, particularly those with difficulty controlling postprandial blood glucose levels and/or body weight. TRIAL REGISTRATION: www.ClinicalTrials.gov identifiers: NCT00042458, NCT00108004.