• Robert R Henry, Paresh Dandona, Jeremy Pettus, Sunder Mudaliar, John Xu, and Lars Hansen.
• University of California, San Diego, California.
• Diabetes Obes Metab. 2017 Jun 1; 19 (6): 814-821.

AimsTo investigate the effects of total daily insulin dose (TDD) reductions on 24-hour continuously monitored mean glucose and fasting β-hydroxybutyrate (a marker for diabetic ketosis/ketoacidosis [DKA]) levels, using patient-level data from a 14-day, pilot study of dapagliflozin in type 1 diabetes (T1DM).MethodsA post hoc exploratory correlation analysis was performed to determine the relationship between change in TDD and (1) 24-hour mean glucose, assessed by continuous glucose monitoring, and (2) fasting β-hydroxybutyrate, in 70 patients with T1DM receiving insulin and dapagliflozin (1, 2.5, 5 or 10 mg) or placebo. The pharmacodynamic effect of dapagliflozin was estimated as a virtual "insulin dose" using 24-hour urinary glucose excretion values and a recognized insulin-to-carbohydrate counting technique.ResultsTrends for correlations were observed between change in TDD and 24-hour glucose (day 7: r = -0.264, P = .056) and β-hydroxybutyrate (day 7: r = -0.187, P = .133; day 14: r = -0.274, P = .047). The pharmacodynamic effect of dapagliflozin 5 or 10 mg was estimated as equivalent to ~20% of baseline TDD. Higher mean and maximum β-hydroxybutyrate levels were observed on days 7 and 14 in patients with a TDD reduction >20% vs ≤20%.ConclusionsOver 14 days, decreasing the insulin dose diminished the glucose-lowering effect of dapagliflozin-insulin combination therapy and increased levels of β-hydroxybutyrate. While insulin dose adjustments should always be individualized, these analyses suggest that, as a general rule, TDD reduction in dapagliflozin-treated patients with T1DM should not exceed 20%, to ensure glycaemic control does not deteriorate and to mitigate the potential for an increased risk of DKA.© 2017 John Wiley & Sons Ltd.

41 keywords...

hide…