Fixed ratio dosing of pramlintide with regular insulin before a standard meal in patients with type 1 diabetes

M C Riddle, K C J Yuen, T W de Bruin, K Herrmann, J Xu, P Öhman, O G Kolterman, M C Riddle, K C J Yuen, T W de Bruin, K Herrmann, J Xu, P Öhman, O G Kolterman

Abstract

Amylin is co-secreted with insulin and is therefore lacking in patients with type 1 diabetes. Replacement with fixed ratio co-administration of insulin and the amylin analogue pramlintide may be superior to separate dosing. This concept was evaluated in a ratio-finding study. Patients with type 1 diabetes were enrolled in a randomized, single-masked, standard breakfast crossover study using regular human insulin injected simultaneously with pramlintide 6, 9 or 12 mcg/unit insulin or placebo. Insulin dosage was reduced by 30% from patients' usual estimates. Plasma glucose, glucagon and pramlintide and adverse events were assessed. All ratios reduced 0-3-h glucose and glucagon increments by >50%. No hypoglycaemia occurred. Adverse events were infrequent and generally mild. All pramlintide/insulin ratios markedly and safely reduced glycaemic excursions and suppressed glucagon secretion in the immediate postprandial state. Further study using one of these ratios to explore the efficacy and safety of longer-term meal-time and basal hormone replacement is warranted.

Trial registration: ClinicalTrials.gov NCT01708044.

Keywords: amylin; pramlintide; type 1 diabetes.

© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
(A) Postprandial glucose, (B) glucagon and (C) pramlintide concentrations over time for each treatment group. Black squares, solid line = placebo + insulin; white squares, dashed line = pramlintide 6 mcg/U insulin; black circles, solid line = pramlintide 9 mcg/U insulin; white triangles, dotted line = pramlintide 12 mcg/U insulin. LS, least squares; s.d., standard deviation; s.e., standard error. aTime point 0 represents predose, defined at each visit as the average of values collected <30 min before dosing. Comparisons versus placebo: *p < 0.001 (all pramlintide doses); †p < 0.01 (all pramlintide doses); ‡p < 0.01 (pramlintide 6 mcg/U insulin); §p < 0.01 (pramlintide 9 mcg/U insulin); ||p < 0.05 (pramlintide 12 mcg/U insulin).

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Source: PubMed

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