Type 1 Diabetes Mellitus
Conditions
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.
Interventions
DRUGInsulin
Standard of care insulin for pump or injection and serves as a control
DRUGSemaglutide
Injectable weekly GLP-1RA given as open label experimental drug
DRUGDapagliflozin
Oral daily SGLT2 Inhibitor given as experimental drug
DRUGPlacebo to Dapagliflozin
Placebo to Dapagliflozin given as a control to the experimental drug
Sponsors
State University of New York at Buffalo
University of Glasgow
Juvenile Diabetes Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This will be a two-center, randomized, open-label then double-blind, parallel group, placebo and standard of care controlled prospective study in type 1 diabetes.
Intervention model description
This will be a two-center, randomized, open-label then double-blind, parallel group, placebo and standard of care controlled prospective study in type 1 diabetes.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 hypoglycemia | 12 months | Change in percent Time in hypoglycemia Level 1 (54-70mg/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 |
| Fructosamine indices | 12 months | Assessment of fructosamine |
| Weekly fasting glucose indices | 12 months | Assessment of change of weekly fasting glucose |
| Insulin requirement indices | 12 months | Assessment of the change in insulin requirement |
| 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. |
| 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. |
| 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. |
| Diastolic Blood pressure assessment | 12 months | Anti-hypertensive effects including change in diastolic BP on dapagliflozin and semaglutide compared to SOC therapy. |
| 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. |
| Level 2 hypoglycemia assessment | 12 months | Differences in rates of hypoglycemic events Level 2 (\<54mg/dl) between triple therapy and in standard therapy arm. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Diabetic ketoacidosis assessment | 12 months | Differences in rates of diabetic ketoacidosis defined as Blood pH \<7.3 in investigative arms. |
Countries
United States
Contacts
STUDY_DIRECTORHusam Ghanim, PhD
State University of NY at Buffalo
Outcome results
None listed