Dipeptidyl Peptidase-4 Inhibitors and Alpha-cell Recovery

Effects of 6 Weeks Treatment With a Dipeptidyl Peptidase 4 Inhibitor on Counterregulatory and Incretin Hormones During Acute Hypoglycaemia in Patients With Type 1 Diabetes: a Randomized Double Blind Placebo-controlled Cross-over Study

Hypoglycaemia is a well-known complication of insulin treated diabetes. The counterregulatory response to hypoglycaemia, with glucagon as the most important mediator, is initially diminished within a few years of onset of Type 1 diabetes and subsequently lost and thus increasing the risk of hypoglycaemia. Dipeptidyl Peptidase (DPP)-4 inhibitors augment the glucagon response to insulin-induced hypoglycaemia in type 2 diabetes. The investigators hypothesize that treatment with a DPP-4 inhibitor in patients with type 1 diabetes will recover the alpha cell response to hypoglycaemia.

The 16 type 1 patients will be randomised to one of two treatment sequences: DPP-4 inhibitor followed by placebo or placebo followed by a DPP-4 inhibitor. Each treatment period lasts 6 weeks, so all patients will receive treatment for 12 weeks in total. Induction of hypoglycaemia will take place at 0 weeks, 6 weeks and 12 weeks to determine the glucagon response.

Inclusion Criteria:

• Type 1 Diabetes Mellitus 5-20 years duration
• C-peptide negative
• Willing and able to give written informed consent

Exclusion Criteria:

• Impaired awareness of hypoglycaemia
• BMI > 27 kg/m2
• Evidence of severe diabetes complications (autonomic neuropathy, macroalbuminuria, proliferative retinopathy)
• Acute illness within 3 months before the study
• Significant renal impairment (creatinine clearance < 50ml/min)
• Use of beta-adrenoreceptor blockers
• Cardiac history (previous arrhythmia)
• History of epilepsy