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

Central South University

Status and phase: Completed; Phase 4

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Saxagliptin; Drug: Metformin; Drug: Insulin; Drug: Vitamin D3

Study type: Interventional

Funder types: Other

Identifiers

NCT02407899

NCRCMD LADA SAX 2015

Details and patient eligibility

About

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) .

Full description

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).

Enrollment: 300 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

300 participants in 3 patient groups

Metformin (and insulin) + saxagliptin

Experimental group

Description:

Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5mg/d and Metformin 1.5g/d (and insulin at individual dose) for 104-week.

Treatment:

Drug: Insulin

Drug: Metformin

Drug: Saxagliptin

Metformin(insulin)+saxagliptin +vitamin D3

Experimental group

Description:

Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5 mg/d, vitamin D drop 2000IU/d, Metformin 1.5g/d (and insulin at individual dose) for 104-week.

Treatment:

Drug: Vitamin D3

Drug: Insulin

Drug: Metformin

Drug: Saxagliptin

Metformin (and insulin)

Active Comparator group

Description:

Patients who have diagnosed LADA are assigned to receive Metformin 1.5g/d(and insulin at individual dose) for 104-week.

Treatment:

Drug: Insulin

Drug: Metformin