Vildagliptin Versus Dapagliflozin on Glucagon

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to assess if vildagliptin and dapagliflozin have dissociated effects on glucagon secretion after a mixed meal ingestion in metformin-treated subjects with type 2 diabetes and whether this is associated with effects on glucose homeostasis.

Detailed Description
-----------------
The aim of the study is to assess if vildagliptin and dapagliflozin have dissociated effects on glucagon secretion after a mixed meal ingestion in metformin-treated subjects with type 2 diabetes and whether this is associated with effects on glucose homeostasis. Subjects will therefore be treated with vildagliptin or dapagliflozin as add-on to metformin for two weeks followed by a meal test in which glucagon levels will be determined.

Official Title
-----------------
Study of the Effect of Vildagliptin Versus Dapagliflozin on Glucagon Response to Mixed Meal in Metformin-treated Subjects With Type 2 Diabetes

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Vildagliptin
* Drug: Dapagliflozin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written consent has been given. Patients with type 2 diabetes treated with a stable dose of metformin during the last three months Age 20-70 years. HbA1c 6.5-8.5% (48-67 mmol/mol) at visit 1. Ability to complete the study Exclusion Criteria: Use of other glucose-lowering therapy than metformin within three months prior to visit 1. A history of any secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly. Type 1 diabetes, positive GAD antibodies Estimated glomerular filtration rate <60 ml/min Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 Any history of recent (<2 weeks) recurrent or severe hypoglycemic episodes. Any history of acute pancreatitis Any history of anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Liver disease such as cirrhosis or chronic active hepatitis History of coronary heart disease or heart failure class III or IV Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks. Treatment with growth hormone of chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1. Use of other investigational drugs at visit 1 or within 30 days of visit 1, unsuitable for the study Hypersensitivity to vildagliptin or dapagliflozin or any compound in the tablet core

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vildagliptin first<br>Treatment with vildagliptin 50mg twice daily for two weeks followed by four weeks washout and then treatment with dapagliflozin 10mg once daily for two weeks | Drug: Vildagliptin<br>* Vildagliptin added at 50 mg twice daily for two weeks followed by four weeks washout and then dapagliflozin 10mg once daily for two weeks<br>* Other names: Galvus;Drug: Dapagliflozin<br>* Dapagliflozin added at 10 mg once daily for two weeks followed by four weeks washout and then vildagliptin 50 mg twice daily for two weeks<br>* Other names: Forxiga;|
| Active Comparator: Dapagliflozin first<br>Treatment with dapagliflozin 10 mg once daily for two weeks followed by four weeks washout and then treatment with vildagliptin 50 mg twice daily for two weeks | Drug: Vildagliptin<br>* Vildagliptin added at 50 mg twice daily for two weeks followed by four weeks washout and then dapagliflozin 10mg once daily for two weeks<br>* Other names: Galvus;Drug: Dapagliflozin<br>* Dapagliflozin added at 10 mg once daily for two weeks followed by four weeks washout and then vildagliptin 50 mg twice daily for two weeks<br>* Other names: Forxiga;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon Response to Meal | Area under the curve (AUC) of the 180 min glucagon levels after mixed meal ingestion (0, 5, 10, 15, 30, 45, 60, 75, 90, 120, 150,180 and 240 minutes post-dose) | 240 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incretin Hormones | Area under the curve (AUC) of the 180 min glucagon like peptide-1 levels after mixed meal (0, 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180 and 240 minutes post-dose) | 240min |