Back to resultsEffects of Dapagliflozin+Saxagliptin in Addition to Metformin v/s Saxagliptin or Dapagliflozin in Patients With DM2.
Primary Purpose
Type2 Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Dapagliflozin 10mg
Saxagliptin 5mg
Saxagliptin 5mg + Dapagliflozin 10 mg
Sponsored by
About this trial
This is an interventional treatment trial for Type2 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Males and females
- Age = 35-70 years
- BMI ≤ 40 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months
- Type 2 diabetes (HbA1c > 7 % and < 10 %)
- Metformin on stable dose (at least 1500 mg/day) for at least 12 weeks before screening and at study initiation.
- Subjects who are women of childbearing potential must agree to utilize a highly effective contraceptive measure throughout the course of the study.. 7.7. Subjects are capable of giving informed consent
Exclusion Criteria:
- Drugs known to affect glucose metabolism (other than metformin) for more than14 days during the 12 weeks before screening
- Known Dapagliflozin and Saxagliptin Excipient Hypersensitivity
- Type 1 Diabetes or History of Ketoacidosis
- history of cancer of any type;
- cerebrovascular or symptomatic peripheral vascular disease;
- heart disease class III or IV NYHA;
- Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m 2 or serum creatinine > 1.5mg/dL in men or >1.4mg/dL in women
- Liver function enzymes higher more than two times the upper limit
- Ongoing urinary tract infection
- drug or alcohol abuse;
- life expectancy <3 yrs
- blood pressure >160/100 mmHg
- Donation of blood to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 8 weeks prior to the enrollment visit and at least 8 weeks thereafter
- Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study (estrogen and/or progesterone treatment)
- Women who are pregnant or breastfeeding
- Patient with a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose an unacceptable risk to the patient or interfere with trial procedures
Sites / Locations
- Department of Endocrinology and Metabolism, University of Pisa
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Dapagliflozin 10mg
Saxagliptin 5mg
Saxagliptin 5 mg + dapagliflozin 10 mg
Arm Description
Dapagliflozin inhibits SGLT2 promoting the excretion of glucose in the urine,and lowers the plasma glucose concentration. This class of drugs has been shown to effectively reduce the HbA1c at all stages of T2DM and can be used in combination of all other anti-diabetic agents including insulin.
Saxagliptin is a DPP4 inhibitor.In patients with type 2 diabetes,administration of saxagliptin led to inhibition of DPP4 enzyme activity.After an oral glucose load,this DPP4 inhibition resulted in a increase in circulating levels of active incretin hormones include GLP-1 and GIP, decreased glucagon concentrations and increased glucose-dependent beta-cell responsiveness,which resulted in higher insulin and C-peptide concentrations.The rise in insulin from pancreatic beta-cells and the decrease in glucagon from pancreatic alpha-cells were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.Saxagliptin improves glycaemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.
Please see Arm 1 and 2
Outcomes
Primary Outcome Measures
Glucose Metabolism
To determine the effect of the combination of dapagliflozin (a SGLT2-inhibitor) and saxagliptin (a DPP-4 inhibitor) on pancreatic hormones secretion and endogenous glucose production in Type 2 diabetic subjects through comparison of the effects of co-administration of Saxagliptin and Dapagliflozin vs. Saxagliptin or Dapagliflozin alone.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03714594
Brief Title
Effects of Dapagliflozin+Saxagliptin in Addition to Metformin v/s Saxagliptin or Dapagliflozin in Patients With DM2.
Official Title
A Randomized Study of the Effects of Dapagliflozin+Saxagliptin in Addition to Metformin Versus Single Addition Saxagliptin or Dapagliflozin on Glucose Metabolism in Patients With DM2 Poorly Controlled With Metformin
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
July 24, 2018 (Actual)
Primary Completion Date
August 31, 2022 (Actual)
Study Completion Date
August 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pisa
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
A phase IV, randomized, double-blind, single center pilot study in subjects with type 2 diabetes poorly controlled with metformin therapy will be randomized to receive, on top of metformin: saxagliptin (5 mg/day) and dapagliflozin (10 mg/day) (Group 1);saxagliptin (5 mg/day) and placebo (Group 2); dapagliflozin (10 mg/day) and placebo (Group 3) for 4 weeks.
Detailed Description
Dapagliflozin (Forxiga) currently is approved for the treatment of T2DM (6). Dapagliflozin inhibits SGLT2, promote the excretion of 80-90 grams of glucose per day in the urine, and lower the plasma glucose concentration. This class of drugs has been shown to effectively reduce the HbA1c at all stages of T2DM and can be used in combination of all other anti-diabetic agents including insulin.
Saxagliptin is a highly potent DPP4 inhibitor.In patients with type 2 diabetes, administration of saxagliptin led to inhibition of DPP4 enzyme activity for a 24-hour period.After an oral glucose load,this DPP4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), decreased glucagon concentrations and increased glucose-dependent beta-cell responsiveness, which resulted in higher insulin and C-peptide concentrations.The rise in insulin from pancreatic beta-cells and the decrease in glucagon from pancreatic alpha-cells were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.Saxagliptin improves glycaemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type2 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dapagliflozin 10mg
Arm Type
Active Comparator
Arm Description
Dapagliflozin inhibits SGLT2 promoting the excretion of glucose in the urine,and lowers the plasma glucose concentration. This class of drugs has been shown to effectively reduce the HbA1c at all stages of T2DM and can be used in combination of all other anti-diabetic agents including insulin.
Arm Title
Saxagliptin 5mg
Arm Type
Active Comparator
Arm Description
Saxagliptin is a DPP4 inhibitor.In patients with type 2 diabetes,administration of saxagliptin led to inhibition of DPP4 enzyme activity.After an oral glucose load,this DPP4 inhibition resulted in a increase in circulating levels of active incretin hormones include GLP-1 and GIP, decreased glucagon concentrations and increased glucose-dependent beta-cell responsiveness,which resulted in higher insulin and C-peptide concentrations.The rise in insulin from pancreatic beta-cells and the decrease in glucagon from pancreatic alpha-cells were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.Saxagliptin improves glycaemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.
Arm Title
Saxagliptin 5 mg + dapagliflozin 10 mg
Arm Type
Active Comparator
Arm Description
Please see Arm 1 and 2
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10mg
Other Intervention Name(s)
forxiga
Intervention Description
Dapagliflozin inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2) which are responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter mechanism causes blood glucose to be eliminated through the urine.[
Intervention Type
Drug
Intervention Name(s)
Saxagliptin 5mg
Other Intervention Name(s)
Onglyza
Intervention Description
Inhibits DPP-4 and slows inactivation of incretin hormones, thereby increasing blood concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus
Intervention Type
Drug
Intervention Name(s)
Saxagliptin 5mg + Dapagliflozin 10 mg
Other Intervention Name(s)
No other intervention name specified
Intervention Description
Please see Intervention 1 and 2
Primary Outcome Measure Information:
Title
Glucose Metabolism
Description
To determine the effect of the combination of dapagliflozin (a SGLT2-inhibitor) and saxagliptin (a DPP-4 inhibitor) on pancreatic hormones secretion and endogenous glucose production in Type 2 diabetic subjects through comparison of the effects of co-administration of Saxagliptin and Dapagliflozin vs. Saxagliptin or Dapagliflozin alone.
Time Frame
from first day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females
Age = 35-70 years
BMI ≤ 40 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months
Type 2 diabetes (HbA1c > 7 % and < 10 %)
Metformin on stable dose (at least 1500 mg/day) for at least 12 weeks before screening and at study initiation.
Subjects who are women of childbearing potential must agree to utilize a highly effective contraceptive measure throughout the course of the study.. 7.7. Subjects are capable of giving informed consent
Exclusion Criteria:
Drugs known to affect glucose metabolism (other than metformin) for more than14 days during the 12 weeks before screening
Known Dapagliflozin and Saxagliptin Excipient Hypersensitivity
Type 1 Diabetes or History of Ketoacidosis
history of cancer of any type;
cerebrovascular or symptomatic peripheral vascular disease;
heart disease class III or IV NYHA;
Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m 2 or serum creatinine > 1.5mg/dL in men or >1.4mg/dL in women
Liver function enzymes higher more than two times the upper limit
Ongoing urinary tract infection
drug or alcohol abuse;
life expectancy <3 yrs
blood pressure >160/100 mmHg
Donation of blood to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 8 weeks prior to the enrollment visit and at least 8 weeks thereafter
Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study (estrogen and/or progesterone treatment)
Women who are pregnant or breastfeeding
Patient with a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose an unacceptable risk to the patient or interfere with trial procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefano Del prato
Organizational Affiliation
University of Pisa
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Endocrinology and Metabolism, University of Pisa
City
Pisa
ZIP/Postal Code
56124
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
Effects of Dapagliflozin+Saxagliptin in Addition to Metformin v/s Saxagliptin or Dapagliflozin in Patients With DM2.
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