Empagliflozin, an inhibitor of the sodium glucose co-transporter 2 (SGLT2), reduces
post-prandial glucose levels in adults with both type 2 and type 1 diabetes and importantly
reduces both cardiovascular and renal complications in type 2 diabetes. In adults with type 1
diabetes empagliflozin improves endothelial function and vascular stiffness when used in
conjunction with insulin. There is clear evidence that complications in type 1 diabetes have
their origins during adolescents thus to reduce diabetic complications with adjunctive
therapy, this age group must be studied. These studies will need to focus on the effects of
these adjunctive agents on functional biomarkers for development of complications. This study
is designed to develop pilot and feasibility data for a large scale trial of low dose
empagliflozin, 2.5 mg daily, on biomarkers for the development of cardiovascular and renal
complications in adolescents between 12 and 18 years of age. The investigators will
specifically study the effects of 8 weeks of empagliflozin on:
1. Pre-and post-prandial inflammatory markers using high carbohydrate and high fat meals.
Inflammatory markers to be measured include interleukin-6 (IL-6), tissue necrosing
factor α (TNF-α), complement component C3 concentrations and skin advanced glycosylation
endproducts (AGE).
2. Pre-and post-prandial vascular function including forearm vascular resistance,
endothelial function and pulse wave velocity.
3. Microalbuminuria and pre- and post-prandial glomerular hyperfiltration, tubular injury
and renal inflammation.
The investigators will, also, measure more traditional risk markers including blood pressure,
hemoglobin A1c, and lipids. Eligible participants will have had diabetes for at least 1 year
and not have other chronic medical illnesses or diabetes complications. Because of the risk
of diabetic ketoacidosis (DKA) subjects must have a hemoglobin A1c level less than 9% and
have no history of recurrent DKA or known insulin omission. This will be the first pilot
study designed to explore primary endpoints regarding cardiovascular and renal disease rather
than glucose control with empagliflozin therapy in adolescents with type 1 diabetes.