Triple Therapy in T1DM

University at Buffalo (UB)

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: Placebo to Dapagliflozin; Drug: Semaglutide; Drug: Insulin; Drug: Dapagliflozin

Study type: Interventional

Funder types: Other

Identifiers

NCT03899402

1987

STUDY00002775

Details and patient eligibility

About

To assess whether the addition of dapagliflozin to semaglutide and insulin (triple therapy) improves glycemic control in patients with type 1 diabetes compared with semaglutide and insulin (dual therapy) and insulin only (standard) treatment.

Full description

This will be a 52 week study for type 1 diabetics looking into the effect of semaglutide and dapagliflozin on HbA1c and glycemic control.

Enrollment: 78 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Type 1 Diabetes for at least 1 year on staple use of continuous subcutaneous insulin infusion (CSII) or multiple daily (four or more) injections (MDI) of insulin for last 3 months.
2. C-peptide <0.23 nM
3. Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII
4. Regularly measuring blood sugars four or more times daily.
5. HbA1c of >7.5%.
6. Well versed in CHO counting*
7. Age 18-70 years.
8. BMI ≥25 kg/m2.

Exclusion criteria

1. Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY
2. Previous use of any agent other than insulin for treatment of diabetes in the last 3 months.
3. History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 3 month prior to the screening visit
4. Frequent episodes of severe hypoglycemia as defined by more than one episode requiring medical assistance, emergency care (paramedics or emergency room care), and/or glucagon therapy administered by a third-party individual within 1 month prior to the screening visit
5. Symptoms of poorly controlled diabetes that would preclude participation in this trial
6. Subjects on a commercial weight loss program with ongoing weight loss, or on an intensive exercise program
7. History of bariatric surgery or lap-band procedure within 12 months prior to screening
8. History of Addison's disease or chronic adrenal insufficiency
9. History of diabetes insipidus
10. Hepatic disease or cirrhosis with Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN) and/or Alanine aminotransferase (ALT) > 3X ULN
11. Serum Total Bilirubin > 2X ULN unless exclusively caused by Gilbert's Syndrome
12. Hemoglobin < 11.0 g/dL (110 g/L) for men; hemoglobin < 10.0 g/dL (100 g/L) for women.
13. Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 3 months or patients with congestive heart failure.
14. ESRD on hemodialysis; and or e-GFR < 60 ml/min/1.73m2
15. HIV or Hepatitis B/C positive status
16. Any other life-threatening, noncardiac disease
17. History of pancreatitis
18. Women who are pregnant or women of childbearing potential who are not using adequate contraception or who are breast feeding
19. Inability to give informed consent
20. History of gastroparesis
21. History of medullary thyroid carcinoma or MEN 2 syndrome
22. History of serious hypersensitivity reaction to these agents
23. Painful gallstones
24. Alcoholism
25. Hypertriglyceridemia (>500 mg/dl)
26. Recurrent genital mycotic infection.
27. Hypovolemic patients or with chronic renal insufficiency.
28. Patients with any malignancy except treated in situ malignancy and basal cell carcinoma of the skin
29. Unexplained hematuria
30. Patients with a history of diabetic retinopathy
31. Use of an investigational agent or therapeutic regimen within 30 days of study
32. Participation in any other concurrent interventional clinical trial

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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78 participants in 4 patient groups, including a placebo group

Control

Active Comparator group

Description:

Standard of care insulin will be used as an active comparator arm for 1/3 of patients (38 patients) for the entire duration of the study.

Treatment:

Drug: Insulin

Dual Therapy

Experimental group

Description:

Once a week injection of Semaglutide (a GLP-1 receptor agonist) in addition to standard of care insulin for the first six months in 2/3 of patients (76 patients). Semaglutide is a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector. Semaglutide will be started at the 0.25 mg dose for the first two weeks, then increased to 0.5 mg at week 2, and then yet again increased to 1.0 mg at week 4.

Treatment:

Drug: Insulin

Drug: Semaglutide

Triple therapy

Experimental group

Description:

Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of Dapagliflozin (an SGLT-2 inhibitor) added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Dapagliflozin will be started at 5 mg for one week, and then increased to 10 mg for the remainder of the study

Treatment:

Drug: Dapagliflozin

Drug: Insulin

Drug: Semaglutide

Triple therapy control

Placebo Comparator group

Description:

Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of the Placebo form of Dapagliflozin added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)).

Treatment:

Drug: Insulin

Drug: Semaglutide

Drug: Placebo to Dapagliflozin