Control of Postprandial Hyperglycemia in Type 1 Diabetes by 24-Hour Fixed-Dose Coadministration of Pramlintide and Regular Human Insulin: A Randomized, Two-Way Crossover Study

Matthew C. Riddle, Rajaa Nahra, Jenny Han, Jessica Castle, Kathryn Hanavan, Marcus Hompesch, David Huffman, Poul Strange, Peter Öhman

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

OBJECTIVE: Healthy pancreatic β-cells secrete the hormones insulin and amylin in a fixed ratio. Both hormones are lacking in type 1 diabetes, and postprandial glucose control using insulin therapy alone is difficult. This study tested the pharmacodynamic effects of the amylin analog pramlintide and insulin delivered in a fixed ratio over a 24-h period.

RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes were stabilized on insulin pump therapy with insulin lispro before a randomized, single-masked, two-way crossover, 24-h inpatient study in which regular human insulin was administered with pramlintide or placebo using separate infusion pumps in a fixed ratio (9 μg/unit). Meal content and timing and patient-specific insulin doses were the same with each treatment. The primary outcome measure was change in mean glucose by continuous glucose monitoring (CGM). Profiles of laboratory-measured glucose, insulin, glucagon, and triglycerides were also compared.

RESULTS: Mean 24-h glucose measured by CGM was lower with pramlintide versus placebo (8.5 vs. 9.7 mmol/L, respectively; P = 0.012) due to a marked reduction of postprandial increments. Glycemic variability was reduced, and postprandial glucagon and triglycerides were also lower with pramlintide versus placebo. Gastrointestinal side effects were more frequent during use of pramlintide; no major hypoglycemic events occurred with pramlintide or placebo.

CONCLUSIONS: Coadministration of fixed-ratio pramlintide and regular human insulin for 24 h improved postprandial hyperglycemia and glycemic variability in patients with type 1 diabetes. Longer studies including dose titration under daily conditions are needed to determine whether this regimen could provide long-term improvement of glycemic control.

Original languageEnglish (US)
Pages (from-to)2346-2352
Number of pages7
JournalDiabetes Care
Volume41
Issue number11
DOIs
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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