The Effect of HMG-CoA Reductase Inhibition on Postprandial GLP-1 Secretion

Not Applicable

Completed

• Conditions: Diabetes Mellitus, Type 2; Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Interventions: Other: Placebo; Drug: Atorvastatin

• Registration Number: NCT03018444
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

The primary objective of the present study is to evaluate the effect of HMG-CoA reductase inhibition during 14 days on the postprandial plasma GLP-1 response in healthy individuals. Secondary objectives include the evaluation of HMG-CoA reductase inhibition on postprandial glucose tolerance, gallbladder emptying, gastric emptying, plasma responses of lipids, bile acids and pancreatic and enteric hormones known to influence glucose metabolism and appetite, and faecal content of bile acids and gut microbiota composition.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-10
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Study First Submitted: 2017-01-10
• Study First Submitted QC: 2017-01-10
• Study First Posted: 2017-01-12
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-02
• Last Update Posted: 2017-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

Inclusion Criteria

• Body mass index (BMI) >18.5 kg/m2 and <35 kg/m2
• Caucasian ethnicity
• Normal haemoglobin
• Glycated haemoglobin (HbA1c) <43 mmol/mol
• Fasting plasma glucose <6 mmol/l
• Informed and written consent

Exclusion Criteria

• Diabetes
• First-degree relatives with diabetes (both type 1 diabetes and type 2 diabetes)
• Liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder
• Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
• Reduced kidney function or nephropathy (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (based on serum creatinine) and/or albuminuria
• Taking any kind of medicine on a regular basis
• Intake of antibiotics two months prior to study
• Active or recent malignant disease
• Any treatment or condition requiring acute or sub-acute medical or surgical intervention
• Any condition considered incompatible with participation by the investigators
• If the subjects receive any antibiotic treatment while included in the study they will be excluded

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	2 weeks treatment with placebo tablets of comparable sizes and color to the Atorvastatin tablets (1st week one tablet once daily, 2nd week two tablets once daily)
Atorvastatin	Atorvastatin	2 weeks treatment with Atorvastatin (1st week 40 mg once daily on day, 2nd week 80 mg (2x40mg) once daily)

Primary Outcome Measures

Name	Time	Method
Postprandial GLP-1 secretion	240 min

Secondary Outcome Measures

Name	Time	Method
Gallbladder emptying	240 min
Postprandial Glucose Tolerance	240 min
Postprandial plasma lipid response	240 min
Postprandial GIP secretion	240 min
Enteric hormones known to influence glucose metabolism	240 min
Postprandial total plasma Bile Acid	240 min
Postprandial Bile Acid Composition	240 min
Faecal content of bile acid	One sample collected on day 12 or 13 of the intervention
Gut microbiota composition	One sample collected on day 12 or 13 of the intervention
Gastric emptying	240 min
Resting Energy Expenditure	At time -20 min, +60 min and +220 min

Trial Locations

Locations (1)

University Hospital, Gentofte, Copenhagen; 🇩🇰 Hellerup, Region Hovedstaden, Denmark