DPP-4 Inhibition, Incretins and Islet Function (CODI24)

Comparison of Three DPP-4 Inhibitors on 24 Hour Blood Glucose, Incretin Hormones and Islet Function in Patients With Type 2 Diabetes

Hypothesis is that DPP-4 inhibition affects glucose levels through changes in incretin and islet hormones. The study examines this in relation to breakfast, lunch and dinner over an entire 24h study period by the use of three different DPP-4 inhibitors and placebo.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Saxagliptin; Drug: Sitagliptin; Drug: Vildagliptin

Detailed Description

The study is a single-center study with a cross-over design to examine glycemia, incretin hormones and islet hormones over a 24h study period with standardized breakfast, lunch and dinner after administration of placebo, saxagliptin, vildagliptin or sitagliptin.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 22185
    • Clinical Research Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Caucasian men or women with type 2 diabetes diagnosed according to ICD10 at time of inclusion

  • Ongoing treatment with life style adjustment including diet and exercise regimen together with metformin as oral antidiabetic . Metformin therapy should be stable the last three months
  • Age 40-75 years
  • HbA1c 52-80 mmol/mol (inclusive)
  • BMI: 20-40 kg/m2
  • Written informed consent has been given
  • Capability and willingness to participate in the whole study

Exclusion Criteria:

• • Liver disease (K70-77 in ICD10) or liver enzymes three times above upper reference range

  • Diabetic nephropathy (GFR < 30 mL/min/1.73 m2 or albuminuria) or other causes of renal disease
  • Proliferative diabetic retinopathy
  • Treatment with any glucose-lowering medication except metformin
  • Previous myocardial infarction, coronary heart disease or instable angina pectoris in the last 6 months.
  • Symptomatic heart failure (NYHA class II-III)
  • Previous surgery on the gastrointestinal tract
  • Larger surgical intervention during the last 12 weeks
  • Female subject who are pregnant or breast feeding
  • Women of child bearing potential not using a highly effective method of birth control
  • Treatment with oral steroids, thiazide diuretics, digoxin or growth hormone
  • Hypersensitivity to the active substances of to any of the excipients
  • Participation in another study the last 4 weeks
  • Smoker
  • Paracetamol intolerance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saxagliptin; Ssaxagliptin is given before breakfast	Drug: Saxagliptin; Saxagliptin (5 mg) is given before breakfast; Other Names: Onglyza
Experimental: ´Sitagliptin; Sitagliptin is given before breakfast	Drug: Sitagliptin; Sitagliptin (100 mg) is given before breakfast; Other Names: Januvia
Experimental: Vildagliptin; Vildagliptin is given before breakfast	Drug: Vildagliptin; Vildagliptin (50mg) is given before breakfast and dinner; Other Names: Galvus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial glucose	The area under the 180 min curves for plasma glucose after each meal	180 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial insulin and glucagon	The area under the 180 min curves for plasma insulin and glucagon after each meal	180 min
Postprandial glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)	The area under the 180 min curves for plasma GLP-1 and GIP after each meal	180 min

Collaborators and Investigators

• Sponsor: Lund University

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: March 14, 2014
• First Submitted That Met QC Criteria: March 14, 2014
• First Posted (Estimate): March 17, 2014

Study Record Updates

• Last Update Posted (Actual): August 23, 2017
• Last Update Submitted That Met QC Criteria: August 22, 2017
• Last Verified: August 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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Vildagliptin; Saxagliptin
• Other Study ID Numbers: 200A