Dipeptidyl Peptidase-4 Inhibitors and Alpha-cell Recovery

Condition(s) targeted: Type 1 Diabetes; Hypoglycemia

Intervention: Sitagliptin (Drug); Placebo (Drug)

Phase: N/A

Status: Completed

Sponsored by: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Official(s) and/or principal investigator(s):
Frits Holleman, MD,PhD, Principal Investigator, Affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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.

Official title: 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

Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator)

Primary outcome:

Glucagon Response to Acute Hypoglycaemia

Glucagon Response to Acute Hypoglycaemia

Secondary outcome:

Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia

Epinephrine Response to Acute Hypoglycaemia

Norepinephrine Response to Acute Hypoglycaemia

Growth Hormone Response to Acute Hypoglycaemia

Cortisol Response to Acute Hypoglycaemia

Symptomatic Hormone Responses to Acute Hypoglycaemia.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Male.

Criteria:

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

Academic Medical Center, Amsterdam, Noord Holland 1100DD, Netherlands

Starting date: March 2011
Last updated: February 14, 2014