Effects of Dapagliflozin+Saxagliptin in Addition to Metformin v/s Saxagliptin or Dapagliflozin in Patients With DM2.

NCT ID: NCT03714594

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-24
• Study Completion Date: 2022-08-31

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.

Conditions

Type2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Dapagliflozin 10mg

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.

Group Type: ACTIVE_COMPARATOR

Dapagliflozin 10mg

Intervention Type: DRUG

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.\[

Saxagliptin 5mg

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.

Group Type: ACTIVE_COMPARATOR

Dapagliflozin 10mg

Intervention Type: DRUG

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.\[

Saxagliptin 5mg

Intervention Type: DRUG

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

Saxagliptin 5 mg + dapagliflozin 10 mg

Please see Arm 1 and 2

Group Type: ACTIVE_COMPARATOR

Saxagliptin 5mg + Dapagliflozin 10 mg

Intervention Type: DRUG

Please see Intervention 1 and 2

Interventions

Dapagliflozin 10mg

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

Saxagliptin 5mg

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

Saxagliptin 5mg + Dapagliflozin 10 mg

Please see Intervention 1 and 2

Intervention Type: DRUG

Other Intervention Names

forxiga; Onglyza; No other intervention name specified

Eligibility Criteria

Inclusion Criteria

1. Males and females

2. Age = 35-70 years

3. BMI ≤ 40 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months

4. Type 2 diabetes (HbA1c > 7 % and < 10 %)

5. Metformin on stable dose (at least 1500 mg/day) for at least 12 weeks before screening and at study initiation.

6. 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

1. Drugs known to affect glucose metabolism (other than metformin) for more than14 days during the 12 weeks before screening

2. Known Dapagliflozin and Saxagliptin Excipient Hypersensitivity

3. Type 1 Diabetes or History of Ketoacidosis

4. history of cancer of any type;

5. cerebrovascular or symptomatic peripheral vascular disease;

6. heart disease class III or IV NYHA;

7. 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

8. Liver function enzymes higher more than two times the upper limit

9. Ongoing urinary tract infection

10. drug or alcohol abuse;

11. life expectancy <3 yrs

12. blood pressure >160/100 mmHg

13. 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

14. 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)

15. Women who are pregnant or breastfeeding

16. 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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pisa

OTHER

Sponsor Role: lead

Responsible Party

Prof. Stefano Del Prato

Clinical Resercher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefano Del prato

Role: PRINCIPAL_INVESTIGATOR

University of Pisa

Locations

Department of Endocrinology and Metabolism, University of Pisa

Pisa, , Italy

Countries

Italy

Other Identifiers

Saxa-Dapa 1

Identifier Type: -

Identifier Source: org_study_id