Vildagliptin Versus Dapagliflozin on Glucagon

• Sponsor: Lund University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02475070
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Vildagliptin; Drug: Dapagliflozin	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Study of the Effect of Vildagliptin Versus Dapagliflozin on Glucagon Response to Mixed Meal in Metformin-treated Subjects With Type 2 Diabetes
• Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: 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; Other Names: Galvus ; Drug: 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; Other Names: Forxiga
Active Comparator: 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	Drug: 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; Other Names: Galvus ; Drug: 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; Other Names: Forxiga

Outcome Measures

Primary Outcome Measures

1. 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

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lund University	Lund		Sweden	22184

Sponsors and Collaborators

• Lund University

Investigators

• Principal Investigator: Bo Ahren, MD PhD, Lund University

Study Documents (Full-Text)

• Study Protocol - Mar 28, 2016
• Statistical Analysis Plan - Mar 28, 2016

More Information

Publications

None provided.

• Responsible Party: Bo Ahren, Professor, Lund University
• ClinicalTrials.gov Identifier: NCT02475070
• Other Study ID Numbers: 350A
• First Posted: Jun 18, 2015
• Last Update Posted: May 2, 2019
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Dapagliflozin; Vildagliptin

Study Results

Participant Flow

Arm/Group Title	Vildagliptin First	Dapagliflozin First
Arm/Group Description	First intervention vildagliptin 50mg twice daily (2 weeks), Washout (4 weeks), Second intervention dapagliflozin 10mg once daily (2 weeks)	First intervention dapagliflozin 10mg once Daily (2 weeks), washout (4 weeks), second intervention with vildaglipitn 50mg twice Daily (2 weeks)
Period Title: Overall Study
STARTED	17	11
COMPLETED	17	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Vildagliptin First	Dapagliflozin First	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	17	11	28
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	17 100%	11 100%	28 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (7.3)	61 (6.7)	63 (7.1)
Sex: Female, Male (Count of Participants)
Female	13 76.5%	7 63.6%	20 71.4%
Male	4 23.5%	4 36.4%	8 28.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	17 100%	11 100%	28 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Sweden	17 100%	11 100%	28 100%

Outcome Measures

1. Primary Outcome

Title	Glucagon Response to Meal
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vildagliptin Treatment	Dapagliflozin Treatment
Arm/Group Description	Vildagliptin 50mg twice daily for 2 weeks	Dapagliflozin 10mg once Daily for 2 weeks
Measure Participants	28	28
Mean (Standard Error) [nmol/l min]	39.0 (2.6)	38.8 (2.7)

2. Secondary Outcome

Title	Incretin Hormones
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vildagliptin Treatment	Dapagliflozin Treatment
Arm/Group Description	Vildagliptin 50mg twice daily for 2 weeks	Dapagliflozin 10mg once daily for 2 weeks
Measure Participants	28	28
Mean (Standard Error) [nmol/l min]	3.8 (0.5)	3.7 (0.5)

Adverse Events

Time Frame	2 weeks
Arm/Group Title	Vildagliptin		Dapagliflozin
Arm/Group Description	Treatment with vildagliptin 50mg twice daily for two weeks		Treatment with dapagliflozin 10 mg once daily for two weeks
All Cause Mortality
	Vildagliptin		Dapagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Serious Adverse Events
	Vildagliptin		Dapagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Vildagliptin		Dapagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/28 (14.3%)		5/28 (17.9%)
Infections and infestations
common cold	1/28 (3.6%)	1	1/28 (3.6%)	1
Metabolism and nutrition disorders
Thirst	1/28 (3.6%)	1	2/28 (7.1%)	2
Musculoskeletal and connective tissue disorders
Myalgia	2/28 (7.1%)	2	1/28 (3.6%)	1
Nervous system disorders
Fatigue	1/28 (3.6%)	1	1/28 (3.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.