Fuling Yunhua Granules and Dihuang Baoyuan Granules in Adults With Type 2 Diabetes and Poor Glycemic Control Despite Lifestyle Intervention

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of Fuling Yunhua Granules and Dihuang Baoyuan Granules in Adult Patients With Type 2 Diabetes Mellitus and Poor Glycemic Control Despite Diet and Exercise Intervention

This trial tests whether Fuling Yunhua Granules and Dihuang Baoyuan Granules, alone or in sequence, lower blood sugar in adults with type 2 diabetes whose blood sugar remains high despite diet and exercise. It will also assess their safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Fuling Yunhua Granules; Drug: Dihuang Baoyuan Granules; Drug: Fuling Yunhua Granules Matched Placebo; Drug: Dihuang Baoyuan Granules Matched Placebo

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled Phase II study. About 150 participants aged 18-70 will be randomly assigned to one of six groups: Fuling Yunhua monotherapy, Dihuang Baoyuan monotherapy, sequential low-dose, sequential high-dose, low-dose placebo, or high-dose placebo. Neither participants nor researchers will know who gets which treatment.

The trial includes a 4-week run-in period (diet and exercise only), 24 weeks of daily treatment, and a 12-week follow-up after stopping treatment. Participants whose blood sugar stays healthy may continue follow-up for up to 52 weeks after stopping treatment.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shen Wu; Phone Number: +86-10-64028110; Email: wushen@tcmlive.com

Study Locations

• China
  • Beijing, China
    • Peking University People's Hospital
    • Contact: Linong Ji, Doctor; Phone Number: +86-10-88324100; Email: jiln@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 to 70 years (inclusive), male or female;
2. Body weight ≥50 kg for men and ≥45 kg for women at both screening and baseline; body mass index (BMI) between 23.0 and 35.0 kg/m2 (inclusive) at both visits;
3. Diagnosed with type 2 diabetes mellitus (T2DM) for at least 3 months according to the diagnostic criteria of the Chinese Guidelines for the Prevention and Treatment of Diabetes;
4. Maintained diet control and exercise therapy for 3 months prior to screening, and did not receive any systemic treatment for diabetes during this period (no prior use of hypoglycemic agents, or prior use of hypoglycemic agents but no use within 3 months before screening);
5. Glycated hemoglobin (HbA1c) ≥7.5% and <11.0% at screening (local laboratory); HbA1c ≥7.0% and <11.0% at baseline (central laboratory);
6. Fasting plasma glucose (FPG) <13.9 mmol/L at both screening and baseline;
7. Traditional Chinese Medicine (TCM) syndrome differentiation consistent with spleen Yin deficiency, Yin deficiency with internal heat accompanied by spleen dampness and stomach heat, and phlegm-fluid retention pattern;
8. Able to understand the procedures and methods of this study, willing to strictly abide by the clinical research protocol to complete this study, maintain the same diet and exercise habits throughout the trial, and voluntarily sign the informed consent form (ICF).

Exclusion Criteria:

1. History of allergic reaction to any component of the study drugs, or history of significant allergic or hypersensitivity reaction to concomitant medications specified in this trial;

2. Non-type 2 diabetes mellitus: type 1 diabetes, gestational diabetes, or special types of diabetes (such as diabetes due to pancreatic injury, Cushing syndrome, or acromegaly);

3. History of acute diabetic complications within 6 months before screening (diabetic ketoacidosis, hyperosmolar hyperglycemic state, or lactic acidosis), requiring treatment as diagnosed by the investigator;

4. Personal or family history of medullary thyroid C-cell hyperplasia, focal hyperplasia, or carcinoma (including sporadic, familial, or localized multiple endocrine neoplasia [MEN] type 2A or 2B syndrome);

5. History of acute or chronic pancreatitis, symptomatic gallbladder disease, or pancreatic injury, or other high-risk factors for pancreatitis deemed unsuitable for this trial by the investigator;

6. History of organ transplantation, or severe autoimmune diseases in the past or present (including but not limited to rheumatoid arthritis, systemic lupus erythematosus, and vasculitis);

7. Diagnosed with malignant tumors within 5 years before screening (except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix), or currently under evaluation for potential malignancy;

8. Thyroid dysfunction that cannot be controlled with stable drug dosage at screening;

9. Any disease that may cause hemolysis or red blood cell instability affecting HbA1c measurement at screening (such as hemolytic anemia or thalassemia);

10. Severe trauma or severe acute infection that may affect glycemic control within 3 months before screening;

11. Severe cardiovascular disease within 6 months before screening, such as heart failure (New York Heart Association [NYHA] grade III-IV), myocardial infarction, coronary artery bypass grafting or percutaneous coronary intervention, sustained and clinically significant arrhythmia (such as second- or third-degree atrioventricular block, or QTcF interval prolongation [≥450 ms in males and ≥470 ms in females]), acute coronary syndrome, transient ischemic attack, hemorrhagic stroke, or ischemic stroke, deemed unsuitable for this trial by the investigator;

12. Diseases that may significantly affect drug absorption, distribution, metabolism and excretion within 6 months before screening: inflammatory bowel disease, peptic ulcer, history of gastrointestinal or rectal bleeding, history of major gastrointestinal surgery (such as gastrectomy, gastrointestinal anastomosis, or intestinal resection), etc.;

13. History of major surgery (intrathoracic, intracranial, abdominal, etc.) within 6 months before screening, or planned surgery during the study that may affect study completion or compliance;

14. Severe hypoglycemic event (Grade 3 or above) or recurrent unexplained hypoglycemic events (at least 3 episodes per month with blood glucose <3.9 mmol/L or symptomatic hypoglycemia) within 6 months before randomization;

15. Use of drugs that may affect glucose metabolism within 2 months before screening, including growth hormone therapy, and long-term or intermittent systemic glucocorticoids (intravenous or oral administration for >2 consecutive weeks or repeated courses, excluding inhaled or topical use), etc.;

16. Use of any immunosuppressant within 6 months before screening, or use of any drug that the investigator judges may affect trial results;

17. Medical or non-medical weight management within 3 months before screening, including unapproved weight management drugs or products, or weight change ≥5% within 3 months before screening (based on participant self-report), or weight change ≥5% (gain or loss) between randomization and screening;

18. Any laboratory test meets any of the following criteria at screening:

    Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of normal (ULN) ×2.5, or total bilirubin (TBIL) > ULN ×1.5; Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated using the CKD-EPI formula; Fasting triglycerides (TG) >5.7 mmol/L; Fasting C-peptide <0.8 ng/mL (or 0.26 nmol/L); Hemoglobin <100 g/L;

19. Hepatitis B surface antigen (HBsAg) positive at screening (if HBsAg positive, HBV DNA testing is required), or hepatitis C virus (HCV) antibody positive, or human immunodeficiency virus (HIV) antibody positive, or Treponema pallidum antibody positive;

20. Blood pressure poorly controlled at screening and baseline (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg);

21. Blood donation or massive blood loss (>400 mL) within 3 months before screening;

22. Participated in any interventional drug clinical trial within 3 months before screening (except screening failures without treatment);

23. Pregnant or lactating women, or men or women of childbearing potential who plan to become pregnant during the study or are unwilling to take medically recognized contraceptive measures;

24. Known or suspected alcohol dependence (defined as >14 units of alcohol per week; 1 unit equals 357 mL beer with 5% alcohol content, 45 mL spirits with 40% alcohol content, or 147 mL wine with 12% alcohol content) or drug abuse at screening;

25. Severe psychiatric disorder or language barrier that prevents adequate understanding and cooperation;

26. Participants who the investigator believes have any other factors that are inappropriate for participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fuling Yunhua Granules Monotherapy Group; Fuling Yunhua Granules, one bag taken orally three times daily before breakfast, lunch and dinner, for 24 weeks.	Drug: Fuling Yunhua Granules; Traditional Chinese herbal medicine granules, 12 g per bag, taken orally before meals.
Experimental: Dihuang Baoyuan Granules Monotherapy Group; Dihuang Baoyuan Granules, one bag taken orally three times daily before breakfast, lunch and dinner, for 24 weeks.	Drug: Dihuang Baoyuan Granules; Traditional Chinese herbal medicine granules, 18 g per bag, taken orally before meals.
Experimental: Sequential Treatment Low-Dose Group; Participants receive Dihuang Baoyuan Granules and Fuling Yunhua Granules alternately every 4 weeks for 24 weeks: Dihuang Baoyuan Granules in weeks 1-4, 9-12 and 17-20, and Fuling Yunhua Granules in weeks 5-8, 13-16 and 21-24. One bag is taken orally twice daily, before breakfast and dinner.	Drug: Fuling Yunhua Granules; Traditional Chinese herbal medicine granules, 12 g per bag, taken orally before meals.; Drug: Dihuang Baoyuan Granules; Traditional Chinese herbal medicine granules, 18 g per bag, taken orally before meals.
Experimental: Sequential Treatment High-Dose Group; Participants receive Dihuang Baoyuan Granules and Fuling Yunhua Granules alternately every 4 weeks for 24 weeks: Dihuang Baoyuan Granules in weeks 1-4, 9-12 and 17-20, and Fuling Yunhua Granules in weeks 5-8, 13-16 and 21-24. One bag is taken orally three times daily, before breakfast, lunch and dinner.	Drug: Fuling Yunhua Granules; Traditional Chinese herbal medicine granules, 12 g per bag, taken orally before meals.; Drug: Dihuang Baoyuan Granules; Traditional Chinese herbal medicine granules, 18 g per bag, taken orally before meals.
Placebo Comparator: Low-Dose Placebo Group; Participants receive placebos matching Dihuang Baoyuan Granules and Fuling Yunhua Granules, administered in the same alternating 4-week sequence and on the same schedule as the sequential treatment groups: Dihuang Baoyuan Granules matched placebo in weeks 1-4, 9-12 and 17-20, and Fuling Yunhua Granules matched placebo in weeks 5-8, 13-16 and 21-24. One bag is taken orally twice daily, before breakfast and dinner, for 24 weeks.	Drug: Fuling Yunhua Granules Matched Placebo; Matched placebo for Fuling Yunhua Granules; identical in appearance (shape, color and packaging), odor and taste, but containing no active herbal components. Granules, 12 g per bag, taken orally before meals.; Drug: Dihuang Baoyuan Granules Matched Placebo; Matched placebo for Dihuang Baoyuan Granules; identical in appearance (shape, color and packaging), odor and taste, but containing no active herbal components. Granules, 18 g per bag, taken orally before meals.
Placebo Comparator: High-Dose Placebo Group; Participants receive placebos matching Dihuang Baoyuan Granules and Fuling Yunhua Granules, administered in the same alternating 4-week sequence and on the same schedule as the sequential treatment groups: Dihuang Baoyuan Granules matched placebo in weeks 1-4, 9-12 and 17-20, and Fuling Yunhua Granules matched placebo in weeks 5-8, 13-16 and 21-24. One bag is taken orally three times daily, before breakfast, lunch and dinner, for 24 weeks.	Drug: Fuling Yunhua Granules Matched Placebo; Matched placebo for Fuling Yunhua Granules; identical in appearance (shape, color and packaging), odor and taste, but containing no active herbal components. Granules, 12 g per bag, taken orally before meals.; Drug: Dihuang Baoyuan Granules Matched Placebo; Matched placebo for Dihuang Baoyuan Granules; identical in appearance (shape, color and packaging), odor and taste, but containing no active herbal components. Granules, 18 g per bag, taken orally before meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Glycated Hemoglobin (HbA1c) at Week 24	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants With Type 2 Diabetes Clinical Remission at 12 Weeks After Discontinuation of Study Drug (Clinical remission defined as HbA1c <6.5%)	12 Weeks After Discontinuation of Study Drug
Change from Baseline in Glycated Hemoglobin (HbA1c) at Weeks 8, 12, 16, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 12, 16, and 12 Weeks After Discontinuation of Study Drug
Proportion of Participants With HbA1c <6.5% at Weeks 8, 12, 16, and 24	Weeks 8, 12, 16, and 24
Proportion of Participants With HbA1c <7.0% at Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 4, 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in 2-Hour Postprandial Glucose (PPG) at Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Continuous Glucose Monitoring (CGM) Time in Range (TIR) at Week 24	Baseline and Week 24
Change from Baseline in Continuous Glucose Monitoring (CGM) Time Below Range (TBR) at Week 24	Baseline and Week 24
Change from Baseline in Continuous Glucose Monitoring (CGM) Time Above Range (TAR) at Week 24	Baseline and Week 24
Change from Baseline in Insulin Sensitivity (HOMA-IS) at Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Beta-Cell Function (HOMA-β) at Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in C-Peptide Index (CPI) at Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Fasting Lipid Profile (Total Cholesterol [TC], LDL-C, HDL-C, Triglycerides [TG]) at Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Systolic and Diastolic Blood Pressure at Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Serum Uric Acid at Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Fasting Body Weight at Weeks 4, 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 4, 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Waist Circumference at Weeks 4, 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 4, 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Hip Circumference at Weeks 4, 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 4, 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in TCM Syndrome Score and Proportion of Participants by TCM Efficacy (Cured, Markedly Effective, Effective, Ineffective) at Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 12, 16, 24, and 12 Weeks After Discontinuation of Study Drug
Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug	Baseline and Weeks 8, 16, 24, and 12 Weeks After Discontinuation of Study Drug

Other Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Biomarkers (Telomere and Mitochondria) at Week 24	Baseline and Week 24
Proportion of Participants Achieving Type 2 Diabetes Clinical Remission at 24, 36, and 52 Weeks After Discontinuation of Study Drug	24, 36, and 52 Weeks After Discontinuation of Study Drug

Collaborators and Investigators

• Sponsor: Beijing Supreme Life Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): November 20, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): March 15, 2028

Study Registration Dates

• First Submitted: October 28, 2026
• First Submitted That Met QC Criteria: November 3, 2026
• First Posted (Actual): November 5, 2026

Study Record Updates

• Last Update Posted (Actual): November 5, 2026
• Last Update Submitted That Met QC Criteria: November 3, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2
• Other Study ID Numbers: JYHS-BAII-Pro-25001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

There is no plan to make individual participant data (IPD) available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No