Elsevier

Endocrine Practice

Volume 15, Issue 7, November–December 2009, Pages 689-695
Endocrine Practice

Original Article
Continuous Subcutaneous Pramlintide Infusion Therapy In Patients With Type 1 Diabetes: Observations From A Pilot Study

https://doi.org/10.4158/EP09044.ORR1Get rights and content

ABSTRACT

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 μg/h. After 3 days, premeal bolus doses of pramlintide were initiated at 15 μg and titrated to 60 μg 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 μg 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. (Endocr Pract. 2009;15:689-695)

Section snippets

INTRODUCTION

Pramlintide, a soluble analogue of amylin, was approved by the US Food and Drug Administration in April 2005 for bolus premeal administration in patients with diabetes mellitus 1., 2.. Subcutaneous injection of pramlintide reduces postprandial glucagon secretion (3), slows gastric emptying (4), and increases satiety (5). In clinical studies, pramlintide has reduced postprandial glucose and triglyceride excursions, hemoglobin A1c (A1C), and body weight in patients with type 1 diabetes 4., 6., 7.

RESEARCH DESIGN AND METHODS

This 16-week, single-arm pilot study enrolled 11 patients with long-term type 1 diabetes who had maintained an A1C level between 7.0% and 10.0% for at least 6 months with routine clinical diabetes care. Eligible patients provided informed consent and had no advanced nephropathy or proliferative retinopathy, took no medications affecting insulin sensitivity, and had received no pramlintide therapy during the preceding 6 months.

After initial physical and laboratory assessments, the study patients

RESULTS

The demographic characteristics of the study population are summarized in Table 1. Changes in weight, A1C, waist circumference, and fasting plasma glucose level at 4-week intervals are shown in Figure 1. The weight change was -0.43 ± 3.04 kg (mean ± SEM) by week 16 (Fig. 1 A). The A1C reached a nadir of -0.45% ± 0.61% (Fig. 1 B); the mean change at week 16 was -0.35% ± 0.62%. The change in waist circumference was -6.2 ± 3.9 cm by week 16 (Fig. 1 C). None of these changes reached statistical

DISCUSSION

In this small pilot study, patients with type 1 diabetes tolerated basal-bolus pramlintide infusion without adverse effects beyond those typically seen in patients with type 1 diabetes during mealtime pramlintide treatment. Patients in this study received premeal pramlintide doses recommended by the manufacturer for patients with type 1 diabetes in addition to basal pramlintide at 216 ng/24 hours, yielding a total daily pramlintide dose of 396 μg. This daily pramlintide dose exceeds the 360 μg

CONCLUSION

The weaknesses of this study include the absence of a comparable control group, the small cohort, and the absence of dietary intake histories sufficient to calculate actual bolus insulin use throughout the study interval. Larger, controlled studies of continuous pramlintide infusion are needed to distinguish the relative effects of basal and bolus pramlintide on postprandial glucose and triglyceride changes and to determine optimal basal doses for pramlintide. Study cohorts that could be

DISCLOSURE

Dr. Huffman has participated in a speaker panel for and received research funding from Amylin Pharmaceuticals, Inc. The other authors have no multiplicity of interest to disclose.

ACKNOWLEDGMENT

This study received funding from Amylin Pharmaceuticals, Inc. and was conceived, written, and conducted solely by the listed authors. Material support was provided by Animas Corporation and LifeScan, Inc.

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Published as a Rapid Electronic Article in Press at http://www.endocrinepractice.org on June 22, 2009. DOI: 10.4158/EP09044.ORR1 © 2009 AACE.

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