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PLoS One. 2015 Nov 6;10(11):e0141085. doi: 10.1371/journal.pone.0141085. eCollection 2015.

Diurnal Glycemic Patterns during an 8-Week Open-Label Proof-of-Concept Trial of Empagliflozin in Type 1 Diabetes.

Author information

1
Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.
2
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
3
Department of Medicine, Division of Nephrology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
4
Boehringer Ingelheim Canada Ltd./Ltée, Burlington, ON, Canada.
5
WHO Collaborating Center, Minneapolis, Minnesota, United States of America.
6
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States of America.
7
Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany.
8
Boehringer Ingelheim Norway K.S, Asker, Norway.

Abstract

BACKGROUND:

We recently reported improved glycemic control with reduced insulin dose in subjects with type 1 diabetes treated with the sodium glucose co-transporter-2 inhibitor empagliflozin. To further characterize the effects, we analyzed diurnal glycemic patterns by continuous glucose monitoring (CGM).

METHODS:

In an 8-week single-arm open-label pilot study of empagliflozin, we compared ambulatory glucose profiles produced from CGM data during 2-week intervals in a placebo run-in baseline period, end-of-treatment, and post-treatment. Change in glycemic exposure was evaluated by area under the median curve according to time of day (AUCTOTAL 12:00am-11:55pm; AUCDAY 7:05am-10:55pm, AUCNIGHT 11:00pm-7:00am), as well as glycemic variability, glycemic stability and time-in-target (≥70 to ≤140mg/dL).

RESULTS:

The 40 patients (26 on insulin pump) were aged 24±5 years and BMI 24.5±3.2 kg/m2. Consistent with the observed HbA1c decrease (8.0±0.9% to 7.6±0.9%, p<0.0001), normalized AUCTOTAL CGM decreased from 153.7±25.4 to 149.0±30.2mg/dL∙h at end-of-treatment (p = 0.31), and significantly increased post-treatment (164.1±29.5mg/dL∙h, p = 0.02). The numerical decrease in normalized AUCNIGHT (152.0±36.6 to 141.9±34.4mg/dL∙h, p = 0.13) exceeded AUCDAY (154.5±24.5 to 152.6±30.4mg/dL∙h, p = 0.65). Trends toward lower glycemic variability (83.1±18.9 to 75.6±28.6mg/dL, p = 0.06) and little change in glycemic stability (10.8±3.6 to 10.3±4.5mg/dL/h, p = 0.51) were observed. When empagliflozin was discontinued, these worsened relative to baseline (89.3±19.3mg/dL, p = 0.04 and 11.8±3.7mg/dL/hr, p = 0.08). Time-in-target numerically increased (40.2±11.9 to 43.1±13.5%, p = 0.69) at end-of-treatment but reversed post-treatment. Findings were similar on stratification of pump and MDI subjects.

CONCLUSIONS:

We observed that empagliflozin was associated with patterns of improved nighttime glycemia more prominent than daytime.

TRIAL REGISTRATION:

Clinicaltrials.gov NCT01392560.

PMID:
26544192
PMCID:
PMC4636141
DOI:
10.1371/journal.pone.0141085
[Indexed for MEDLINE]
Free PMC Article

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