Protective Effects of Saxagliptin (And Vitamin D3) on β Cell Function in Adult-onset Latent Autoimmune Diabetes

The main purpose of this study is to evaluate whether saxagliptin or (and vitamin D3) with metformin (and insulin) therapy can better protect islet β cell function than metformin(and insulin) .

LADA is actually a form of type 1 diabetes, which is caused by autoimmune damage of islet β cells and triggered by environmental factors based on genetic susceptibility. LADA shows some characteristics of type 2 diabetes at its onset, which develops slowly and latent, and easily be misdiagnosed as type 2 diabetes due to slowly β cell function deterioration. This is a multi-center, open- label, 1:1:1 randomized controlled trial to investigate the protective effects of saxagliptin and vitamin D3 in LADA patients. The study comprises the 0-6weeks of screening period and the 104-week intervention period. After obtaining the informed consent，the screening will find out the eligible patients according to the inclusion/exclusion criteria, then the patients will be randomized to the 104-week intervention period. Subjects will be randomized into one of the three groups(arms) through central dynamic randomization: metformin (and insulin), metformin(and insulin) +saxagliptin, metformin(and insulin) +saxagliptin+vitamin D3. Our previous randomized- controlled pilot study showed that dipeptidyl peptidase 4 (DPP-4) inhibitors could significantly improve islet β-cell function in patients with LADA. The main purpose of this study: To evaluate whether saxagliptin (and vitamin D3) with metformin (and insulin) therapy can better protect islet β cell function than metformin (and insulin).

Eligibility Criteria:
Inclusion Criteria:

1. Volunteer to participate in the study with informed consent;
2. The LADA patients to be included in this study are defined as:

(1) Meet the 1999 WHO Diagnostic Criteria for Diabetes Mellitus; (2) Age at diagnosis of DM ≧ 18 years old; (3) Glutamic acid decarboxylase antibody (GADA) positive; (4) Serum fasting C-peptide ≥ 100 pmol/L or 2-hour postprandial C-peptide≥ 200 pmol/L; 3. Age between 18-70 years old; 4. Diabetes duration \<4 year; 5. Outpatient or inpatient.

Exclusion Criteria:

1. Pregnancy, breastfeeding or planned pregnancy within two years;
2. Gestational diabetes mellitus or other specific types of diabetes;
3. Allergic to saxagliptin, vitamin D3 and their excipient;
4. Treatment with any anti-diabetic medication other than insulin in the last 8 weeks prior to randomization;
5. Use of systemic corticosteroids therapy (oral, intravenous) continuously for more than 7 days over the past 6 months;
6. Treatment with cytochrome P450 3A4/5 (CYP450 3A4/5) inhibitor;
7. Alanine aminotransferase (ALT) or aspartate transaminase(AST) more than 3 times of the normal upper limit, total bilirubin (TBIL) more than 2 times of the normal upper limit;
8. Creatinine levels ≧ 1.5 mg/dL(132μmol/L) for males and ≧ 1.4 mg/dL (123μmol/L) for females or creatinine clearance ≦ 50 mL/min;
9. History of malignant tumors;
10. History of mental disorders;
11. History of alcohol abuse or illegal drug abuse;
12. Serious systemic disease which the investigators think would not be suitable for the study.