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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Intervention / Treatment: Other: Placebo; Drug: Atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Region Hovedstaden
    • Hellerup, Region Hovedstaden, Denmark, 2900
      • University Hospital, Gentofte, Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin; 2 weeks treatment with Atorvastatin (1st week 40 mg once daily on day, 2nd week 80 mg (2x40mg) once daily)	Drug: Atorvastatin; Atorvastatin tablet
Placebo Comparator: 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)	Other: Placebo; Placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Postprandial GLP-1 secretion	240 min

Secondary Outcome Measures

Outcome Measure	Time Frame
Postprandial Bile Acid Composition	240 min
Postprandial total plasma Bile Acid	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
Gallbladder emptying	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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Principal Investigator: Filip K. Knop, Professor MD, Department of Clinical Medicine, University of Copenhagen, Gentofte Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: January 10, 2017
• First Posted (Estimate): January 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 2, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: H-16034243