Efficacy and Safety of Hebenrun in Patients With Type 2 Diabetes

Evaluation of the Efficacy and Safety of Hebenrun in Patients With Type 2 Diabetes Mellitus: A Randomized Controlled Trial

This study aims to evaluate the efficacy and safety of Hebenrun (a functional food based on natural grain bran) combined with metformin in patients with type 2 diabetes mellitus (T2DM). The study hypothesis is that Hebenrun combined with metformin will achieve a higher complete discontinuation rate of oral hypoglycemic drugs compared to metformin alone. A total of 110 T2DM patients will be randomly assigned (1:1) to the study group (metformin + Hebenrun) or the control group (metformin alone) and followed for 48 weeks. The primary outcome is the complete discontinuation rate of oral hypoglycemic drugs at the end of follow-up.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and insufficient insulin secretion, and has become a major global public health problem. According to the International Diabetes Federation (IDF), the number of T2DM patients aged 20-79 reached 537 million in 2021, accounting for 10.5% of the global population. Long-term hyperglycemia can lead to multi-system damage, inducing cardiovascular disease, stroke, blindness, renal failure, and foot ulcers, causing disability and shortening life expectancy, and bringing huge socioeconomic burden.

Conventional interventions for T2DM include oral hypoglycemic agents, insulin, and incretin-based hypoglycemic drugs, but overall blood glucose control in the population is not optimistic. According to the Chinese Guidelines for the Prevention and Treatment of Diabetes (2024 Edition), the awareness rate, treatment rate, and control rate of diabetes have improved slowly. Even with combined oral medications and insulin therapy, half of patients still fail to achieve the target glycated hemoglobin level, and the risk of long-term microvascular and macrovascular complications is significantly increased. The hypoglycemic capacity of existing drugs is limited, and multi-drug combinations significantly increase the risk of adverse reactions (such as hypoglycemia and gastrointestinal symptoms). Insufficient compliance (especially with insulin injections) is also a bottleneck in blood glucose management. Therefore, finding effective, safe, and highly compliant food substitution therapies is of great significance.

Hebenrun is a functional food formulated primarily with natural grain bran as the main ingredient. Preliminary pre-experiments have found that it has hypoglycemic effects. When used in combination with Western medicine, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin can all be reduced, and after gradually reducing the Western medicine dosage, blood glucose can still be maintained at normal or near-normal levels. This study aims to evaluate the efficacy and safety of Hebenrun on blood glucose control in T2DM patients through standardized clinical observation, providing evidence-based support for its rational application.

This is a single-center, randomized, parallel-group, open-label superiority controlled trial. Eligible T2DM patients will be randomly assigned (1:1) to the study group (metformin tablets + Hebenrun) or the control group (metformin tablets). Both groups will use the same metformin tablet dose adjustment regimen, with a total enrollment of 110 patients (55 per group). Follow-up time points are 0 weeks (baseline), week 4, week 8, week 12, week 24, week 36, and week 48. This trial protocol is written in accordance with the SPIRIT clinical trial protocol reporting standards.

Inclusion Criteria:

1. Meets the Western medicine diagnostic criteria for type 2 diabetes (T2DM), referring to the Chinese Guidelines for the Prevention and Treatment of Diabetes (2024 Edition). If typical diabetes symptoms are present (such as polydipsia, polyuria, polyphagia, unexplained weight loss), meeting any one of the following can confirm the diagnosis: fasting blood glucose (FBG) ≥7.0 mmol/L; random blood glucose ≥11.1 mmol/L; oral glucose tolerance test (OGTT) 2-hour blood glucose ≥11.1 mmol/L; glycated hemoglobin (HbA1c) ≥6.5%. If typical diabetes symptoms are lacking, two of the above blood glucose indicators at the same time point or at two different time points (excluding random blood glucose) need to reach or exceed the diagnostic cut-off point to diagnose diabetes.
2. Age 18-65 years, glycated hemoglobin (HbA1c): 6.5%-8.5%.
3. Good patient compliance, cooperation with treatment and follow-up.
4. The research has been approved by the hospital ethics committee, and all patients voluntarily participate and sign informed consent.

Exclusion Criteria:

1. Type 1 diabetes, gestational diabetes, and special types of diabetes.
2. History of acute diabetic complications (ketoacidosis, hyperosmolar coma, lactic acidosis).
3. Major organ diseases (severe heart, liver, kidney dysfunction), malignant tumors, or severe mental disorders.
4. Contraindications or allergy history to any component of Hebenrun.
5. Psychotropic drug dependence, accompanied by obvious anxiety or depression tendencies.
6. Women preparing for pregnancy, during pregnancy, and lactation.
7. Expected poor compliance or language communication dysfunction.
8. Already enrolled or about to enroll in other clinical studies.

Withdrawal/Discontinuation Criteria:

1. Subjects actively request withdrawal.
2. Unable to contact during follow-up.
3. Adverse reactions or disease changes making it unsuitable to continue participation.
4. The researcher determines that continued participation is detrimental to the subject.
5. Unable to follow the prescribed treatment regimen or unable to persist with medication.