Background: This study was designed to determine whether pramlintide added to insulin therapy reduced the risks associated with extreme blood glucose (BG) fluctuations in patients with type 1 diabetes.
Methods: Self-monitored BG (SMBG) records were retrospectively analyzed from a randomized, double-blind, placebo-controlled study of the effects of pramlintide on intensively treated patients with type 1 diabetes. Two groups--pramlintide (n=119), 30/60 microg administered subcutaneously at each meal, or placebo (n=129)--were matched by age, gender, and baseline hemoglobin A1C. Using SMBG, daily BG profiles, BG rate of change, and low and high BG indices (LBGI and HBGI, respectively) measuring the risk for hypoglycemia and hyperglycemia were calculated.
Results: Compared with placebo, pramlintide significantly attenuated the pre- to postprandial BG rate of change (F=83.8, P<0.0001). Consequently, in pramlintide-treated patients, the average post-meal BG (8.4 vs. 9.7 mmol/L [151.2 vs. 174.6 mg/dL]) and postprandial HBGI were significantly lower than placebo (both P<0.0001). Substantial daily BG variation was observed in placebo-treated patients, with most significant hyperglycemia occurring after breakfast and during the night; post-meal BG did not vary significantly throughout the day in pramlintide-treated patients. The reduction in postprandial hyperglycemia in pramlintide-treated patients occurred without increased risk for preprandial hypoglycemia as quantified by the LBGI.
Conclusions: Risk analysis of the effect of pramlintide treatment demonstrated risk-reduction effects independent of changes in average glycemia, most notably reduced rate and magnitude of postprandial BG fluctuations. These effects were not accompanied by an increased risk of hypoglycemia.
Trial registration: ClinicalTrials.gov NCT00107107.