The Effect of Saxagliptin on Glucose Fluctuation and Immune Regulation in Patients With Type 1 Diabetes
Overview
- Phase
- Phase 4
- Intervention
- Saxagliptin
- Conditions
- Type 1 Diabetes
- Sponsor
- Nanjing Medical University
- Enrollment
- 184
- Locations
- 1
- Primary Endpoint
- Change of Mean amplitude of glycemic excursions (MAGE) from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone by continuous glucose monitoring system (CGMS)
- Last Updated
- 9 years ago
Overview
Brief Summary
To investigate whether saxagliptin could reduce the fluctuation of glycemia and improve the glycemic control in those type 1 diabetes through mechanisms of suppressing glucagon secretion, improving beta cell function, and re-regulating of the T cell immune system.
Detailed Description
Type 1 diabetes mellitus (T1DM) is characterized by immune mediated beta-cell destruction. Due to the imbalance between glucagon and insulin, long-term T1DM patients experience frequent hypoglycaemia and high glucose variability despite of multiple daily injections of insulin. Dipeptidyl peptidase 4 (DPP-4) inhibitors are a new class of anti-diabetic agents and are widely used in clinical practice to improve glycemic control and protect β-cell function in patients with type 2 diabetes mellitus(T2DM). Saxagliptin, a DPP-4 inhibitor, improves glycemic control in patients with T2DM by increasing endogenous active, intact glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in response to food, which augments insulin secretion and decreases glucagon release. This mechanism can lead to the reduction of glucose variation. In some pilot studies, incretin-based therapy in patients with T1DM can improve glucose control and reduce hypoglycemia, the mechanism probably is that it regulates glucagon level. In type 1 diabetic mouse models, DPP-4 inhibitors preserves beta-cell mass and stimulating beta-cell replication. Interestingly, DPP-4 is also known as cluster of differentiation antigen 26(CD26).It is expressed on the membrane of many types of lymphocyte, e.g. T, B and natural killer(NK)cells, and is involved in their cellular functions. CD26 plays a key role in many aspects in lymphocyte function beyond its DPP-4 enzymatic activity.These observations make it a promising therapeutic target. Recently, the attention of saxagliptin has been mainly focused on type 2 diabetes, data in type 1 diabetes is rare. We are going to carry out this phase 4 study to testify our hypothesis that saxagliptin could reduce the fluctuation of glycemia and improve the glycemic control in those type 1 diabetes through mechanisms of suppressing glucagon secretion, improving beta cell function, and re-regulating of the T cell immune system.
Investigators
Yang Tao
Department of Endocrinology & Metabolism
Nanjing Medical University
Eligibility Criteria
Inclusion Criteria
- •Provision of informed consent prior to any study specific procedures;
- •Diagnosed with type 1 diabetes;
- •Men or women who are 12 to 65 years of age at time of consenting upon Visit 1.;
- •Positivity for at least one of the four islet autoantibodies(IA-2A、IAA、GADA、ZnT8A);
- •6.5% ≤ HbA1c ≤10.0%.
Exclusion Criteria
- •type 2 diabetes；
- •Evidence of chronic or acute complications of diabetes which is unstable and requires hospitalization；
- •Evidence of disease stress；
- •History of administration of any antihyperglycemic therapy (other than insulin) during the 12 weeks prior to Visit 1；
- •Have a history of, or currently have, acute or chronic pancreatitis；
- •Immunocompromised individuals such as patients that have undergone organ transplantation or patients diagnosed with HIV or patients with agranulocytosis；
- •Evidence of chronic or acute infection；
- •Active liver disease and/or significant abnormal liver function defined as Aspartate transaminase(AST) ≥3x Upper Limit of Normal(ULN) and/or Alanine aminotransferase (ALT) ≥3x Upper Limit of Normal(ULN)；
- •History of unstable or rapidly progressing renal disease, creatinine clearance(CrCl) ≤50ml/min;
- •Congestive heart failure defined as New York Heart Association (NYHA) class III or IV and/or left ventricular ejection fraction of ≤ 40%；
Arms & Interventions
insulin+Saxagliptin
Patients who have diagnosed type 1 diabetes are assigned to receive Saxagliptin tablets 5 mg and insulin for 24-week.
Intervention: Saxagliptin
insulin+Saxagliptin
Patients who have diagnosed type 1 diabetes are assigned to receive Saxagliptin tablets 5 mg and insulin for 24-week.
Intervention: Insulin
insulin
Patients who have diagnosed type 1 diabetes only use insulin.
Intervention: Insulin
Outcomes
Primary Outcomes
Change of Mean amplitude of glycemic excursions (MAGE) from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone by continuous glucose monitoring system (CGMS)
Time Frame: 24 week
Secondary Outcomes
- Change of C-peptide area under the curve (AUC C-peptide) or fasting C-peptide from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone by 3-hour mixed meal tolerance test(MMTT)(24 week)
- Change of Haemoglobin A1c (HbA1c) from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone(24 week)
- Change of insulin dosage (U/kg/d) from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone(24 week)