The Insulin Response to the Gut Hormone GIP After Near-normalisation of Plasma Glucose in Patients With Type 2 Diabetes

• Status: Recruiting
• Trial end date: 2020-09-01
• Target enrollment: 15
• Participant gender: All

Summary

The investigators hypothesise that the insulinotropic effect of endogenous GIP is improvable in patients with type 2 diabetes after three weeks of near-normalisation of plasma glucose. To test this hypothesis, a randomised, placebo-controlled, double-blinded, crossover study employing a GIP receptor antagonist, will be carried out.

Fifteen overweight (body mass index (BMI) > 25 kg/m2) dysregulated (HbA1c > 59 mmol/mol) patients with type 2 diabetes will attend two experimental days followed by a three-week period of plasma glucose near-normalisation (achieved by standard treatment of type 2-diabetes), followed by another two experimental days. On experimental days, patients will receive an infusion of GIP receptor antagonist or placebo during a 75 g oral glucose tolerance test. The primary endpoint is changes in levels of C-peptide divided by changes in levels of plasma glucose and secondary endpoints include changes in circulating levels of C-peptide, insulin, glucose, GIP, glucagon-like peptide 1 (GLP-1), glucagon and markers of bone turnover as well as indices of beta cell function. Furthermore, gastric emptying rate will be assessed.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Gentofte, Copenhagen
• Treatments: Empagliflozin; Gastric Inhibitory Polypeptide; Insulin; Insulin, Globin Zinc; Metformin

Criteria

Inclusion Criteria:

1. Type 2 diabetes

2. Metformin treatment

3. Haemoglobin A1c (HbA1c) I. > 59 mmol/mol in case the diabetes treatment is only metformin II. 59-75 mmol/mol in case the diabetes treatment is metformin and add-on therapy

4. Body Mass Index (BMI) > 25 kg/m2

5. Age > 18 years

6. Caucasian

7. Normal haemoglobin levels

Exclusion Criteria:

1. Treatment with insulin or GLP-1-receptor agonist

2. Any treatment that cannot be paused for 12 hours

3. Diabetes duration more than 20 years

4. Weekly alcohol intake of more than 14 units for men or 7 units for women of alcohol (of 12 g) or narcotics abuse

5. Liver disease

6. Kidney disease (estimated glomerular filtration rate, eGFR < 60 ml/min/1,73 m2)

7. Unusual dietary preferences or planned weight loss within the duration of the study

8. Any other condition that in the opinion of the responsible investigators is disqualifying.

9. For women I. Current or planned pregnancy for the duration of the study II. Positive pregnancy test at the screening or any of the experimental days III. Women who are currently breastfeeding