Metformin in Post Chronic Pancreatitis Diabetes Mellitus

Phase 4

Recruiting

• Conditions: Chronic Pancreatitis
• Interventions: Drug: Metformin; Drug: Placebo

• Registration Number: NCT06937294
• Lead Sponsor: Changhai Hospital

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of metformin in treating patients with post chronic pancreatitis diabetes mellitus (PPDM-C). The main questions it aims to answer are:

* What is the efficacy of metformin in glycemic control in patients with PPDM-C?

* What is the incidence of adverse effects associated with metformin in patients with PPDM-C?

Participants will be randomly assigned to receive either metformin or a placebo to see if metformin provides significant glycemic control and to assess the safety profile of the treatment.

Detailed Description

Chronic pancreatitis (CP) is an irreversible chronic fibro-inflammatory disease caused by multiple factors. Patients often present with recurrent upper abdominal pain, dyspepsia, steatorrhea, and other symptoms. Typical imaging findings of CP include pancreatic duct calcification, ductal dilation, and parenchymal atrophy. As pancreatic fibrosis progresses, islet cells may also be damaged, leading to abnormal glucose metabolism or even diabetes mellitus (DM). Approximately 25-80% of CP patients develop DM which has been called post chronic pancreatitis diabetes mellitus (PPDM-C), with the prevalence increasing with the duration of CP. PPDM-C has garnered significant attention in the academic community due to its unique clinical manifestations and complications. However, there is currently no well-defined management strategy for PPDM-C.

The management of PPDM-C requires balancing pancreatic endocrine and exocrine functions, and developing individualized treatment strategies. Compared with T2DM patients, PPDM-C patients face greater difficulty in achieving optimal glycemic control. Currently, there is no standardized management for PPDM-C, with treatment protocol largely relying on clinical experience. Metformin is the most frequently used medication for PPDM patients (64.5%), and is typically the initial treatment. In PPDM-C patients, previous metformin use is associated with a survival benefit over those who have never used any antidiabetic drugs. However, there is lake of clinical trails specifically addressing PPDM-C to elucidate the the efficacy in glycemic control and safety of metformin.

Study Timeline

• Study First Submitted: 2025-04-07
• Study First Submitted QC: 2025-04-15
• Study First Posted: 2025-04-22
• Study Start: 2025-04-28
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-21
• Primary Completion: 2025-12-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

1. Aged 18-65 years, any sex.
2. Patients diagnosed with chronic pancreatitis.
3. Diagnose diabetes at least 3 months after chronic pancreatitis diagnosis.
4. Never used any diabetes drug/glucose-lowering medication or had discontinued any glucose-lowering medications for at least 8 weeks prior to screening.
5. HbA1c criteria: 7.5%~9.0%.
6. BMI >18.5.
7. Provision of signed informed consent.

Exclusion Criteria

1. Type 1 diabetes or secondary diabetes not caused by chronic pancreatitis (e.g. diabetes due to monogenic defects, cystic fibrosis, medications, autoimmune diseases, stress, or other factors).
2. Contraindications or history of intolerance or allergy to metformin.
3. Fasting C-peptide <0.3 nmol/L.
4. Acute episodes of chronic pancreatitis at enrollment or within 3 months prior to enrollment.
5. History of congestive heart failure (NYHA class 3 or greater), unstable angina, or other severe cardiovascular diseases.
6. History of cancer (except non-melanoma skin cancer) within 5 years prior to screening.
7. History of partial or total pancreatectomy.
8. History of or planning bariatric surgery.
9. Previous organ transplantation.
10. Treatment with oral or systemic glucocorticoids within 3 months prior to enrollment or plan to use during the study (inhaled steroids are permitted).
11. History of hemolytic anemia, chronic transfusion requirements, or other conditions rendering HbA1c results unreliable.
12. Other conditions requiring glucose-lowering medications, such as polycystic ovary syndrome.
13. Fasting blood glucose >11.1 mmol/L during screening, requiring immediate treatment as judged by the physician.
14. Sever psychiatric disorders or health conditions deemed unsuitable for clinical research participation.
15. Pregnancy or plans for pregnancy during the course of the study.
16. Any other condition considered by the investigator to be inappropriate for participation in the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	Participants are administered metformin with an initial dose of 500 mg/day, which was incrementally increased by 500 mg/day each week until the maximum tolerated dose. The maximum dose of metformin is set at 2000 mg/day. After 2 weeks of administration, participants will undergo safety assessments, including complete blood count, urinalysis, liver function tests, and renal function tests. After attainment to a stable dose of metformin, participants will undergo follow-up assessments at 4 weeks, 8 weeks, and 12 weeks. The final evaluation of outcome measures will be completed at the 12-week follow-up.
Placebo	Placebo	Participants are administered a placebo, starting with one tablet per day, followed by an incremental increase of one tablet per week. In the absence of adverse reactions, the dosage is escalated up to a maximum of four tablets per day. After 2 weeks of administration, participants will undergo safety assessments, including complete blood count, urinalysis, liver function tests, and renal function tests. After attainment to a stable dose, participants will undergo follow-up assessments at 4 weeks, 8 weeks, and 12 weeks. The final evaluation of outcome measures will be completed at the 12-week follow-up.

Primary Outcome Measures

Name	Time	Method
Change from baseline in glycosylated hemoglobin (HbA1c)	12 weeks after the attainment of a stable dose	The change in the value of glycosylated hemoglobin (HbA1c) collected at Week 12 (after the attainment of a stable does) relative to baseline.

Secondary Outcome Measures

Name	Time	Method
Exploratory objectives: scores of quality of life	12 weeks after the attainment of a stable dose	Quality of life scores for patients with chronic pancreatitis are obtained using SF-36 (36-Item Short Form Health Survey) which contains 8 dimensions scored from 0 to 100 (standardized converted scores). The higher score means better function.
The proportion of patients with HbA1c below 6.5% at Week 12	12 weeks after the attainment of a stable dose	At the Week 12 after the attainment of a stable does, the proportions of patients with glycosylated hemoglobin (HbA1c) levels exceeding 6.5% are assessed.
The proportion of patients with HbA1c below 7% at Week 12	12 weeks after the attainment of a stable dose	At the Week 12 after the attainment of a stable does, the proportions of patients with glycosylated hemoglobin (HbA1c) levels exceeding 7% are assessed.
The proportion of patients with HbA1c below 7.5% at Week 12	12 weeks after the attainment of a stable dose	At the Week 12 after the attainment of a stable does, the proportions of patients with glycosylated hemoglobin (HbA1c) levels exceeding 7.5% are assessed.
The incidence of adverse events	12 weeks after the attainment of a stable dose	Adverse events include hypoglycemia, diabetic ketoacidosis, hyperglycemic hyperosmolar state, acute pancreatitis and gastrointestinal symptoms (nausea, vomiting, diarrhea, etc.).
Blood glucose profile characteristics	12 weeks after the attainment of a stable dose	Blood glucose profile from continuous glucose monitoring system (CGMS) (unit: mmol/L or mg/dL).
Exploratory objectives: pancreatic and gut hormones	Baseline	Levels of specific pancreatic hormones (C-peptide, insulin, glucagon, etc.) and gut hormones (ghrelin, gastric inhibitory peptide, glucagon like peptide-1, etc.) measured in venous blood (unit: mmol/L or mg/dL).
Exploratory objectives: pancreatic exocrine function	12 weeks after the attainment of a stable dose	Pancreatic exocrine function is evaluated by fecal elastase-1 test.

Trial Locations

Locations (1)

Changhai Hospital; 🇨🇳 Shanghai, Shanghai, China