Effects of Sitagliptin on Gastric Emptying, Glycaemia and Blood Pressure in Type 2 Diabetes

Royal Adelaide Hospital

Status and phase

Completed

Phase 2

Conditions

Gastroparesis

Diabetes Mellitus

Treatments

Drug: Sitagliptin

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02324010

140916

Details and patient eligibility

About

The purpose of this study is to evaluate the acute effects of sitagliptin on postprandial glycemia, incretin hormones and blood pressure, and the relationship to gastric emptying, after a mashed potato meal in patients with type 2 diabetes.

Full description

The purpose of this study is to (i) evaluate the acute effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin (100mg once daily for two days), on gastric emptying, postprandial plasma glucose, insulin, glucagon and 'incretin' hormones (ie. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)), blood pressure and heart rate after a high carbohydrate meal, and (ii) to determine whether the magnitude of the effects of sitagliptin on postprandial glycaemia and blood pressure is related to the rate of gastric emptying, in patients with type 2 diabetes.

The rate of entry of carbohydrate into the small intestine is especially important in patients with diabetes mellitus. Sitagliptin is an orally administered inhibitor of dipeptidyl-peptidase-IV (DPP-IV), the enzyme responsible for the degradation of GLP-1. It is hypothesized that sitagliptin will increase the GLP-1 response to, and thereby slow gastric emptying and diminish the glycaemic and blood pressure response to, a carbohydrate-containing meal.

Twenty healthy subjects (male and female) will be studied. Each subject will be studied on two occasions following treatment for 2 days with sitagliptin (100mg once daily) or matching placebo in a randomized, double blind, crossover design. Measurements of gastric emptying, intragastric meal distribution, blood glucose concentrations, gut hormones, blood pressure, splanchnic flow and appetite will be measured for 4 hours following ingestion of a mashed potato meal.

Enrollment

14 patients

Sex

All

Ages

40 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet or metformin alone
Body mass index (BMI) 20 - 40 kg/m2
Males and females (females of reproductive potential must be using an appropriate contraceptive method)
Glycated haemoglobin (HbA1c) ≤ 8.5%
Haemoglobin above the lower limit of the normal range (i.e. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (i.e. >10mcg/L)

Exclusion criteria

Subjects with gastrointestinal disease, significant upper or lower gastrointestinal symptoms, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy)
Other significant illness, including epilepsy, cardiovascular or respiratory disease.
History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy.
Impaired renal or liver function (as assessed by calculated creatinine clearance < 50 mL/min using the Cockroft-Gault equation (27) or abnormal liver function tests (> 2 times upper limit of normal range)).
Requirement for medication known to influence blood pressure and/or heart rate and/or gastrointestinal function, drugs with anticholinergic effects
Alcohol consumption > 20 g per day
Smoking > 10 cigarettes per day
Pregnancy or lactation.
Vegetarian
Allergy to sitagliptin or any other 'gliptin'.
Donation of blood within the previous 3 months
Participation in any other research studies within the previous 3 months
Exposure to ionising radiation for research purposes in the previous 12 months
Inability to give informed consent