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Diabetes Obes Metab. 2017 Jun;19(6):814-821. doi: 10.1111/dom.12882. Epub 2017 Mar 27.

Dapagliflozin in patients with type 1 diabetes: A post hoc analysis of the effect of insulin dose adjustments on 24-hour continuously monitored mean glucose and fasting β-hydroxybutyrate levels in a phase IIa pilot study.

Author information

1
University of California, San Diego, California.
2
Veterans Affairs San Diego Healthcare System, San Diego, California.
3
State University of New York at Buffalo, Buffalo, New York.
4
AstraZeneca, Gaithersburg, Maryland.
5
Bristol-Myers Squibb, Princeton, New Jersey.

Abstract

AIMS:

To 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).

METHODS:

A 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.

RESULTS:

Trends 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%.

CONCLUSIONS:

Over 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.

KEYWORDS:

antidiabetic drug; continuous glucose monitoring (CGM); dapagliflozin; glycaemic control; insulin therapy; type 1 diabetes; β-hydroxybutyrate

PMID:
28098426
DOI:
10.1111/dom.12882
[Indexed for MEDLINE]

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