Type 2 Diabetes
Conditions
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.
Interventions
DRUGVildagliptin
Vildagliptin added at 50 mg twice daily for two weeks followed by four weeks washout and then dapagliflozin 10mg once daily for two weeks
DRUGDapagliflozin
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
Sponsors
Lund University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Written consent has been given. 2. Patients with type 2 diabetes treated with a stable dose of metformin during the last three months 3. Age 20-70 years. 4. HbA1c 6.5-8.5% (48-67 mmol/mol) at visit 1. 5. Ability to complete the study
Exclusion criteria
1. Use of other glucose-lowering therapy than metformin within three months prior to visit 1. 2. A history of any secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly. 3. Type 1 diabetes, positive GAD antibodies 4. Estimated glomerular filtration rate \<60 ml/min 5. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 6. Any history of recent (\<2 weeks) recurrent or severe hypoglycemic episodes. 7. Any history of acute pancreatitis 8. Any history of anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. 9. Liver disease such as cirrhosis or chronic active hepatitis 10. History of coronary heart disease or heart failure class III or IV 11. 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. 12. Treatment with growth hormone of chronic oral or parenteral corticosteroid treatment (\> 7 consecutive days of treatment) within 8 weeks prior to visit 1. 13. Use of other investigational drugs at visit 1 or within 30 days of visit 1, unsuitable for the study 14. Hypersensitivity to vildagliptin or dapagliflozin or any compound in the tablet core
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vildagliptin First 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: Vildagliptin added at 50 mg twice daily for two weeks followed by four weeks washout and then dapagliflozin 10mg once daily for two weeks
Dapagliflozin: 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 | 17 |
| Dapagliflozin First 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: Vildagliptin added at 50 mg twice daily for two weeks followed by four weeks washout and then dapagliflozin 10mg once daily for two weeks
Dapagliflozin: 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 | 11 |
| Total | 28 |
Baseline characteristics
| Characteristic | Dapagliflozin First | Total | Vildagliptin First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 28 Participants | 17 Participants |
| Age, Continuous | 61 years STANDARD_DEVIATION 6.7 | 63 years STANDARD_DEVIATION 7.1 | 64 years STANDARD_DEVIATION 7.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 28 Participants | 17 Participants |
| Region of Enrollment Sweden | 11 participants | 28 participants | 17 participants |
| Sex: Female, Male Female | 7 Participants | 20 Participants | 13 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 4 / 28 | 5 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
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)
Time frame: 240 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vildagliptin Treatment | Glucagon Response to Meal | 39.0 nmol/l min | Standard Error 2.6 |
| Dapagliflozin Treatment | Glucagon Response to Meal | 38.8 nmol/l min | Standard Error 2.7 |
Secondary
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)
Time frame: 240min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vildagliptin Treatment | Incretin Hormones | 3.8 nmol/l min | Standard Error 0.5 |
| Dapagliflozin Treatment | Incretin Hormones | 3.7 nmol/l min | Standard Error 0.5 |