Vildagliptin Versus Dapagliflozin on Glucagon

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Vildagliptin; Drug: Dapagliflozin

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 22184
    • Lund University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: June 15, 2015
• First Submitted That Met QC Criteria: June 17, 2015
• First Posted (Estimate): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): May 2, 2019
• Last Update Submitted That Met QC Criteria: January 31, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Vildagliptin
• Other Study ID Numbers: 350A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No