Clinical trial NCT06937294: Metformin in Post Chronic Pancreatitis Diabetes Mellitus
Official title: Metformin in Post Chronic Pancreatitis Diabetes Mellitus: a Double-blind, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Chronic Pancreatitis
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
First posted: 2025-04-22
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized to the experimental group (metformin) or the control group (placebo).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in glycosylated hemoglobin (HbA1c)
timeFrame: 12 weeks after the attainment of a stable dose
Secondary outcomes:
measure: The proportion of patients with HbA1c below 6.5% at Week 12
timeFrame: 12 weeks after the attainment of a stable dose
measure: The proportion of patients with HbA1c below 7% at Week 12
timeFrame: 12 weeks after the attainment of a stable dose
measure: The proportion of patients with HbA1c below 7.5% at Week 12
timeFrame: 12 weeks after the attainment of a stable dose
measure: The incidence of adverse events
timeFrame: 12 weeks after the attainment of a stable dose
measure: Blood glucose profile characteristics
timeFrame: 12 weeks after the attainment of a stable dose
measure: Exploratory objectives: pancreatic and gut hormones
timeFrame: Baseline
measure: Exploratory objectives: pancreatic exocrine function
timeFrame: 12 weeks after the attainment of a stable dose
measure: Exploratory objectives: scores of quality of life
timeFrame: 12 weeks after the attainment of a stable dose
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
affiliation: Changhai Hospital
name: Zhaoshen Li, M.D.
role: STUDY_CHAIR
affiliation: Changhai Hospital
name: Lianghao Hu, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Olesen SS, Viggers R, Drewes AM, Vestergaard P, Jensen MH. Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality in Postpancreatitis Diabetes Mellitus Versus Type 2 Diabetes: A Nationwide Population-Based Cohort Study. Diabetes Care. 2022 Jun 2;45(6):1326-1334. doi: 10.2337/dc21-2531.
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citation: Cho J, Scragg R, Pandol SJ, Goodarzi MO, Petrov MS. Antidiabetic Medications and Mortality Risk in Individuals With Pancreatic Cancer-Related Diabetes and Postpancreatitis Diabetes: A Nationwide Cohort Study. Diabetes Care. 2019 Sep;42(9):1675-1683. doi: 10.2337/dc19-0145. Epub 2019 Jun 21.