Original ArticleContinuous Subcutaneous Pramlintide Infusion Therapy In Patients With Type 1 Diabetes: Observations From A Pilot Study
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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2024, Computer Methods and Programs in BiomedicineAmylin effect in extrapancreatic tissues participating in glucose homeostasis, in normal, insulin-resistant and type 2 diabetic state
2011, PeptidesCitation Excerpt :In order to evaluate the short-term action of amylin in the glucose metabolism of extrapancreatic tissues involved in the regulation of glucose homeostasis, in the present study we have analyzed the effect of a 3-day constant infusion close to physiological doses of amylin in normal rats and in two well characterized experimental rats models, insulin-resistant and type 2 diabetic [5,40]. During amylin treatment, this hormone reached concentrations in plasma slightly over physiological levels, lower though than those being used for therapeutic purpose [19], but similar to those observed in some pathological conditions such as obesity, pregnancy [23] and type 2 diabetes carrying polymorphism in the amylin gene [34]. As expected, the IR model of the present study showed a higher basal plasma insulin levels than those in both T2D and normal rats, which were significantly reduced though after amylin infusion; however, no changes were detected in the latter groups after amylin.
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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.