Triple Therapy in T1DM

Phase 2

Active, not recruiting

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: Insulin; Drug: Semaglutide; Drug: Placebo to Dapagliflozin; Drug: Dapagliflozin

• Registration Number: NCT03899402
• Lead Sponsor: State University of New York at Buffalo

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2019-03-26
• Study First Submitted QC: 2019-03-29
• Study First Posted: 2019-04-02
• Study Start: 2019-05-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-02
• Primary Completion: 2026-01-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 78

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Insulin	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.
Triple therapy control	Insulin	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)).
Dual Therapy	Semaglutide	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.
Triple therapy	Insulin	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
Triple therapy control	Semaglutide	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)).
Triple therapy control	Placebo to Dapagliflozin	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)).
Dual Therapy	Insulin	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.
Triple therapy	Semaglutide	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
Triple therapy	Dapagliflozin	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

Primary Outcome Measures

Name	Time	Method
Change in HbA1c following dapagliflozin	6 months	Change in HbA1c at 6 months following dapagliflozin or placebo therapy in addition to combined semaglutide and insulin treatment.

Secondary Outcome Measures

Name	Time	Method
Systolic Blood pressure assessment after triple therapy	12 months	Anti-hypertensive effects including change in systolic BP on dapagliflozin and semaglutide compared to SOC therapy.
Weekly fasting glucose indices	12 months	Assessment of change of weekly fasting glucose
body weight assessment following triple therapy	12 months	Change in body weight as assessed at 12 months on dapagliflozin and semaglutide compared to SOC therapy.
Urinary ketones assessment	12 months	Differences in rates of diabetic ketoacidosis defined as elevated urine ketones (greater than the upper limit of the normal range) in investigative arms.
Change in HbA1c with semaglutide	6 months	Change in HbA1c from baseline at 6 months in dual therapy group (insulin and semaglutide) compared to insulin only group.
Assessment of hypoglycemia	12 months	Change in percent Time in hypoglycemia Level 1 (54-70mg/dl) as assessed by CGM
Fructosamine indices	12 months	Assessment of fructosamine
Insulin requirement indices	12 months	Assessment of the change in insulin requirement
Blood pressure medication use	12 months	Anti-hypertensive effects including change in numbers of BP medications required in patients dapagliflozin and semaglutide compared to SOC therapy.
Severe (level 3) hypoglycemia assessment	12 months	Differences in rates of hypoglycemic events Level 3 (\<54mg/dl) characterized by altered mental and/or physical status requiring assistance) between triple therapy and in standard therapy arm.
Assessment of hyperglycemia level 1	12 months	Change in percent Time hyperglycemia Level 1(180-250mg/dl) as assessed by CGM
Assessment of hyperglycemia level 2	12 months	Change in percent Time in hyperglycemia Level 2 ( \>250mg/dl) as assessed by CGM
Assessment of percent time glucose in range	12 months	Change in percent Time in Range (70- 180 mg/dl) as assessed by CGM
body weight assessment following dapagliflozin	6 months	Change in body weight at 6 months between dapagliflozin and placebo groups.
body weight assessment following semaglutide	6 months	Change in body weight at 6 months following starting semaglutide compared to standard of care (SOC) group.
Level 1 hyperglycemia assessment	12 months	Differences in rates of Level 1 hyperglycemia (glucose levels \>180mg/dl and \<250mg dl) between triple therapy and in standard therapy arm.
serum ketones assessment	12 months	Differences in rates of diabetic ketoacidosis defined as elevated serum ketones (greater than the upper limit of the normal range) in investigative arms.
Diabetic ketoacidosis assessment	12 months	Differences in rates of diabetic ketoacidosis defined as Blood pH \<7.3 in investigative arms.
Change in HbA1c with triple therapy	12 months	Change in HbA1c from baseline at 12 months in triple therapy group compared to insulin only group.
Diastolic Blood pressure assessment	12 months	Anti-hypertensive effects including change in diastolic BP on dapagliflozin and semaglutide compared to SOC therapy.
Level 2 hypoglycemia assessment	12 months	Differences in rates of hypoglycemic events Level 2 (\<54mg/dl) between triple therapy and in standard therapy arm.
Level 2 hyperglycemia assessment	12 months	Differences in rates of Level 2 hyperglycemia (glucose levels \<250mg dl) between triple therapy and in standard therapy arm.

Trial Locations

Locations (1)

Diabetes and Endocrinology Research Center of WNY; 🇺🇸 Williamsville, New York, United States