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.

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.

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.

This study is a double-blind trail. Participants, investigators, care providers and outcomes assessors are blinded to the group allocations. Investigators and care providers provide guidance on drug use and lifestyle. Outcomes assessors are responsible for the follow-up of the patients. A study coordinator, who is not blinded to the group allocations, is appointed to oversee the coordination of the study and the maintenance of the blinding procedures. The study coordinator do not be allowed to communicate with others (participants, investigators, care providers and outcomes assessors) regarding the group allocations and clinical conditions of the participants. In the event of a serious adverse event, the blinding could be broken by contacting the study coordinator for safety considerations, and the reasons for unblinding were documented in detail.