Effects of Cofrogliptin on Beta-Cell Function in LADA Patients

NCT07460336 | Not Yet Recruiting DMC

• 1 other identifier: KOLA Study
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, randomized, open-label, controlled study aims to evaluate the effect of cofrogliptin on pancreatic β-cell function in adults with latent autoimmune diabetes in adults (LADA). Following a screening period of up to 6 weeks, 84 eligible participants will be randomized in a 1:1 ratio via a sealed-envelope method, stratified by baseline GADA titer (≥0.3 vs \<0.3). Participants will be assigned to one of two treatment arms: (1) metformin (with or without insulin) plus vitamin D3, or (2) metformin (with or without insulin) plus vitamin D3 and cofrogliptin. Cofrogliptin will be administered orally at a dose of 10 mg once every 2 weeks, and vitamin D3 at 2000 IU once daily, for a total treatment duration of 52 weeks. Study visits are planned at baseline and at Weeks 12, 26, 38, and 52, during which mixed-meal tolerance tests (MMTT) and other protocol-specified assessments will be conducted.

Conditions

Latent Autoimmune Diabetes in Adults (LADA)

Keywords

LADA; Adult-Onset Autoimmune Diabetes; DPP-4 inhibitor; Beta-cell Function; Randomized Controlled Trial; C-peptide; Vitamin D3; Cofrogliptin

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 2-hour Mixed-Meal Tolerance Test (MMTT) C-peptide Area Under the Curve (AUC)

  Change from baseline in the area under the curve from 0 to 120 minutes (AUC0-120) for serum C-peptide during a mixed-meal tolerance test (MMTT), calculated using the trapezoidal rule from C-peptide measured at 0, 60, and 120 minutes.

  Baseline, Week 52

Secondary Outcomes (14)

• Change From Baseline in 2-hour MMTT C-peptide AUC at Weeks 12, 26, and 38

  Baseline, Week 12, Week 26, Week 38

• Change From Baseline in Fasting C-peptide (FCP)

  Baseline, Week 12, Week 26, Week 38, Week 52

• Change From Baseline in 60-Minute Post-Meal C-peptide

  Baseline, Week 12, Week 26, Week 38, Week 52

• Change From Baseline in 120-Minute Post-Meal C-peptide

  Baseline, Week 12, Week 26, Week 38, Week 52

• Change From Baseline in Glycated Hemoglobin (HbA1c)

  Baseline, Week 26, Week 52

Other Outcomes (2)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Throughout the study (52 weeks)

• Number of participants with Clinically Significant Abnormal Vital Signs, Laboratory Tests, or ECG Findings

  At scheduled visits through Week 52

Study Arms (2)

Cofrogliptin + Vitamin D3 + Background Therapy

EXPERIMENTAL

Participants will receive Cofrogliptin (10 mg orally every 2 weeks) and Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), over a period of 52 weeks.

Drug: Cofrogliptin; Drug: Vitamin D3; Drug: Metformin; Drug: Insulin

Vitamin D3 + Background Therapy

ACTIVE COMPARATOR

Participants will receive Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), for a total duration of 52 weeks.

Drug: Vitamin D3; Drug: Metformin; Drug: Insulin

Interventions

Cofrogliptin DRUG

5 mg/tablet, oral; 2 tablets (10 mg) once every 2 weeks. Administered from randomization through Week 52.

Cofrogliptin + Vitamin D3 + Background Therapy

Vitamin D3 DRUG

400 IU/capsule, oral; 5 capsules (2000 IU) once daily. Administered from randomization through Week 52.

Cofrogliptin + Vitamin D3 + Background Therapy; Vitamin D3 + Background Therapy

Metformin DRUG

Background therapy. Oral; typical daily dose 1.5 g, adjustable from 1.0 to 1.7 g/day per investigator judgment.

Cofrogliptin + Vitamin D3 + Background Therapy; Vitamin D3 + Background Therapy

Insulin DRUG

Background therapy, as needed. Subcutaneous; individualized daily dose per investigator judgment.

Cofrogliptin + Vitamin D3 + Background Therapy; Vitamin D3 + Background Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Voluntarily signed informed consent.
• \. Age 18 to 70 years, inclusive.
• \. Diagnosed with LADA, defined as meeting all of the following:
• (1) Meets 1999 WHO criteria for diabetes mellitus.
• (2) Age at diagnosis of diabetes ≥ 18 years.
• (3) Positive for at least one islet autoantibody (GADA, IA-2A, or ZnT8A).
• (4) Did not require continuous insulin therapy for at least 6 months after diagnosis.
• \. Stimulated C-peptide ≥ 200 pmol/L.
• \. Glycated Hemoglobin (HbA1c) ≤ 9.0%.
• \. For women of childbearing potential, must agree to use a highly effective method of contraception throughout the study.

You may not qualify if:

• \. Pregnant, breastfeeding, or planning to become pregnant during the study.
• \. Gestational diabetes or other specific types of diabetes.
• \. Known hypersensitivity to Cogliptin, Vitamin D3, or their excipients.
• \. Use of DPP-4 inhibitors, GLP-1 receptor agonists, or thiazolidinediones (TZDs) within 8 weeks prior to randomization.
• \. Hypercalcemia (serum calcium above the upper limit of the normal range).
• \. Systemic corticosteroid therapy (oral or IV) for more than 7 consecutive days within 6 months prior to screening.
• \. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 times the upper limit of normal (ULN), or total bilirubin \> 2 times ULN.
• \. Estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73 m².
• \. History of acute diabetic complications such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state.
• \. History of pancreatitis or pancreatic surgery.
• \. New York Heart Association (NYHA) class III or IV congestive heart failure, or known left ventricular ejection fraction (LVEF) \< 40%.
• \. History of malignancy.
• \. Severe psychiatric illness.
• \. History of alcohol or illicit drug dependence.
• \. Any other severe systemic disease that the investigator deems unsuitable for enrollment.

Sponsors & Collaborators

• Second Xiangya Hospital of Central South University: lead

Study Sites (1)

The Second Xiangya Hospital, Central South University

Changsha, Hunan, 410000, China

Location

MeSH Terms

Conditions

Latent Autoimmune Diabetes in Adults

Interventions

Cholecalciferol; Metformin; Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Biguanides; Guanidines; Amidines; Organic Chemicals; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Zhiguang Zhou, MD,PhD

  The Second Xiangya Hospital, Central South University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiguang Zhou, MD,PhD

CONTACT

+8673185292154; zhouzhiguang@csu.edu.cn

Chuqing Cao, PhD

CONTACT

csuccq@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, National Clinical Research Center for Endocrine and Metabolic Diseases

Model Details: A single-center, randomized, open-label, controlled, parallel-group study with a 1:1 allocation ratio.

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: March 10, 2026
• Study Start: March 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)