Tuesday, June 25, 2013

Empagliflozin - A potential new treatment option for Type 1 diabetes

At ADA 2013, Boehringer Ingelheim presented Phase 1 data on its SGLT2 inhibitor empagliflozin in type 1 diabetes patients.  Empagliflozin when delivered as an adjunctive therapy to basal-bolus insulin regimens, it led to improved glycemic control, reduction in hypglycemia and a decrease in the mean daily dose of insulin. 

Clinical Trial Design

In an 8-week single-arm open-label pilot study of the SGLT2 inhibitor empagliflozin 25 mg po QD in subjects receiving optimized standard of type 1 diabetes care, we evaluated the efficacy on glycemia and rates of hypoglycemia compared to a 2-week placebo run-in period (NCT01392560). Other outcome measures were urinary glucose excretion (UGE), insulin requirement, and anthropometrics. We recruited 42 normoalbuminuric patients (28 insulin pump, 14 multiple daily injection) with mean±SD age 24±5 years, A1c 8.0±0.9 %, and fasting plasma glucose (FPG) 10.0±4.8 mmol/L. 

Clinical Trial Data

40 patients completed 8 weeks of treatment with empagliflozin 
1)  Mean A1c decreased by 0.4% to 7.6±0.9% (p<0 .0001="" nbsp="" p="">
2)  FPG decreased non-significantly to 8.6±3.1 mmol/L (p=0.06). 
3)  Symptomatic hypoglycemia (<3 .0="" 0.04="" 0.12="" day="" declined="" events="" from="" mmol="" p="0.005) </p" per="" to="">
4) Mean daily insulin dose declined from 55±20 to 46±19 U/day from the placebo run in period (p<0 .0001="" nbsp="" p="">
5) The mean UGE increased from 19±19 at baseline to 134±61 g/day at 8 weeks (p<0 .0001="" nbsp="" p="">
6) Weight decreased by 2.7 kg from 72.6±12.7 (p<0 .0001="" and="" nbsp="" p="">
7) Waist circumference decreased by 3.8 cm from 82.9±8.7 (p<0 .0001="" nbsp="" p="">
8) Apart from hypoglycemia, polyuria (79%) and thirst (74%) were the most frequent adverse events. 2 subjects were withdrawn after the early occurrence of diabetic ketoacidosis (one in the setting of gastroenteritis, the other in the setting of insulin pump failure).

Conclusion

In patients with type 1 diabetes, empagliflozin as adjunctive to insulin therapy was generally well-tolerated and associated with short-term improvement in glycemic control, a reduction in rates of hypoglycemia and reduced insulin requirement and body weight. A randomized clinical trial of the efficacy of adjunctive empagliflozin in type 1 diabetes is warranted.

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