Vildagliptin Versus Dapagliflozin on Glucagon

Phase 4

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Dapagliflozin first	Vildagliptin	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
Vildagliptin first	Vildagliptin	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
Vildagliptin first	Dapagliflozin	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
Dapagliflozin first	Dapagliflozin	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

Primary Outcome Measures

Name	Time	Method
Glucagon Response to Meal	240 min	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)

Secondary Outcome Measures

Name	Time	Method
Incretin Hormones	240min	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)