DPP-4 Inhibition, Incretins and Islet Function

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Vildagliptin
* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saxagliptin<br>Ssaxagliptin is given before breakfast | Drug: Saxagliptin<br>* Saxagliptin (5 mg) is given before breakfast<br>* Other names: Onglyza;|
| Experimental: ´Sitagliptin<br>Sitagliptin is given before breakfast | Drug: Sitagliptin<br>* Sitagliptin (100 mg) is given before breakfast<br>* Other names: Januvia;|
| Experimental: Vildagliptin<br>Vildagliptin is given before breakfast | Drug: Vildagliptin<br>* Vildagliptin (50mg) is given before breakfast and dinner<br>* Other names: Galvus;|

What is the study measuring?
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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 |