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

• Published in: PloS one Vol. 10; no. 11; p. e0141085
• Main Authors: Perkins, Bruce A., Cherney, David Z. I., Soleymanlou, Nima, Lee, Justin A., Partridge, Helen, Tschirhart, Holly, Zinman, Bernard, Mazze, Roger, Fagan, Nora, Kaspers, Stefan, Woerle, Hans-Juergen, Broedl, Uli C., Johansen, Odd Erik
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.11.2015; Public Library of Science (PLoS)
• Subjects: Adult; Antidiabetics; Benzhydryl Compounds - therapeutic use; Blood glucose; Blood Glucose - metabolism; Body mass; Circadian Rhythm - physiology; Clinical medicine; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diurnal; Drug dosages; Drug therapy; Endocrinology; Female; Glucose; Glucose monitoring; Glucose transporter; Glucosides - therapeutic use; Health care networks; Hemoglobin; Hospitals; Humans; Hypoglycemia; Hypoglycemic Agents - therapeutic use; Insulin; Male; Medicine; Metabolism; Perkins, David; Pilot Projects; Sodium; Stability; Time of use; Variability; Weight control; Young Adult; Canada; United States > US; Norway; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141085

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). 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). 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. We observed that empagliflozin was associated with patterns of improved nighttime glycemia more prominent than daytime. Clinicaltrials.gov NCT01392560.