Abstract
BackgroundWe 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).MethodsIn 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).ResultsThe 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.ConclusionsWe observed that empagliflozin was associated with patterns of improved nighttime glycemia more prominent than daytime.Trial RegistrationClinicaltrials.gov NCT01392560
Highlights
Akin to studies in type 2 diabetes,[6,7,8] sodium glucose cotransporter-2 (SGLT2) inhibitors may be effective as adjunctive-to-insulin therapy in type 1 diabetes mellitus (T1DM) to favourably improve glycemic control, hypoglycemia risk, and the weight gain associated with over-insulinization.[9,10,11,12,13,14,15]
A potential clinical question linked to SGLT2 inhibitor therapy as adjunctive-to-insulin in T1DM is the degree of possible insulin dose adjustment that may be required upon initiation of treatment to minimize a potential hypoglycemia risk
Trend toward improvement in glycemic exposure that was primarily explained by the improvement observed during nighttime hours despite a decrease in overnight basal insulin delivery; 4) Significant worsening in glycemic exposure and glycemic variability when empagliflozin therapy was discontinued; and 5) A similar magnitude of glycemic impact regardless of insulin pump or multiple daily injection (MDI) use
Summary
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)
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