Effects of Fixed-Ratio Pramlintide and Insulin on Postprandial Hyperglycemia in T1D

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Administration of fixed-dose ratio basal-bolus pramlintide with regular human insulin markedly reduced postprandial glucose and glycemic variability in patients with type 1 diabetes.
Administration of fixed-dose ratio basal-bolus pramlintide with regular human insulin markedly reduced postprandial glucose and glycemic variability in patients with type 1 diabetes.

Coadministration of 24 hours of fixed-ratio pramlintide and regular human insulin improves postprandial hyperglycemia and glycemic variability in patients with type 1 diabetes, according to a study published in Diabetes Care.

Replacement insulin alone is often not sufficient to regulate glycemic control in type 1 diabetes. Despite some success in limiting postprandial hyperglycemia with treatments combining amylin analogue pramlintide and insulin, this approach is not common. To test the pharmacodynamic effects of pramlintide and insulin delivered in a fixed ratio over a 24-hour period, researchers conducted a 2-way inpatient crossover study in which 34 patients with type 1 diabetes (average age, 41 years) were randomly assigned to receive either basal and bolus subcutaneous pramlintide or placebo at 9 μg/unit of infused regular human insulin. Demographic and baseline characteristics were similar between groups.

The primary outcome was 24-hour mean weight glucose measured by continuous glucose monitoring. Compared with the placebo group, intervention participants demonstrated significantly lower 24-hour mean weight glucose (9.7 vs 8.5 mmol/L, respectively; P =.012). The researchers reported that this difference was the result of a marked reduction of postprandial increments of glucose.

Patients who received pramlintide spent less time in the hyperglycemic range (≥10.0 mmol/L) and more time in the target glycemic range (>3.9 to <10.0 mmol/L) than those receiving placebo and demonstrated significantly less glycemic variability (P =.005), including measures like distance traveled (P =.0009), rate of change (P =.016), and total energy (P =.0003). The intervention group also had reduced levels of postprandial glucagon and triglycerides.

Significantly more intervention patients experienced adverse events than those receiving placebo (69% vs 32%, respectively). Of those receiving pramlintide, 47% experienced gastrointestinal events compared with 7% of patients taking placebo. The researchers reported no major hyperglycemic events for either group.

The researchers noted several limitations, including an inability to assess long-term effects and efficacy of a fixed-ratio regimen because of the short duration of the study.

Despite such limitations, the researchers said the results demonstrate that “24-hour administration of fixed-dose ratio basal-bolus pramlintide with regular human insulin markedly reduced postprandial glucose and glycemic variability in patients with type 1 diabetes.”

Reference

Riddle MC, Nahra R, Han J, et al. 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 [published online September 13, 2018]. Diabetes Care. doi:10.2337/dc18-1091

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