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

NCT03714594 | Completed Phase 2

• 1 other identifier: Saxa-Dapa 1
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Type2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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.

  from first day

Study Arms (3)

Dapagliflozin 10mg

ACTIVE COMPARATOR

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.

Drug: Dapagliflozin 10mg

Saxagliptin 5mg

ACTIVE COMPARATOR

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.

Drug: Dapagliflozin 10mg; Drug: Saxagliptin 5mg

Saxagliptin 5 mg + dapagliflozin 10 mg

ACTIVE COMPARATOR

Please see Arm 1 and 2

Drug: Saxagliptin 5mg + Dapagliflozin 10 mg

Interventions

Dapagliflozin 10mg 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.\[

Also known as: forxiga

Dapagliflozin 10mg; Saxagliptin 5mg

Saxagliptin 5mg 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

Also known as: Onglyza

Saxagliptin 5mg

Saxagliptin 5mg + Dapagliflozin 10 mg DRUG

Please see Intervention 1 and 2

Also known as: No other intervention name specified

Saxagliptin 5 mg + dapagliflozin 10 mg

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pisa: lead

Study Sites (1)

Department of Endocrinology and Metabolism, University of Pisa

Pisa, 56124, Italy

Location

MeSH Terms

Interventions

dapagliflozin; saxagliptin

Study Officials

• Stefano Del prato

  University of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Resercher

Study Record Dates

• First Submitted: July 25, 2018
• First Posted: October 22, 2018
• Study Start: July 24, 2018
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: November 8, 2022

Record last verified: 2022-11

Locations

IT (1)