Efficacy and Safety of Sanggua Tablets in the Treatment of Patients With Impaired Glucose Tolerance and Mild Type 2 Diabetes

Efficacy and Safety of Sanggua Tablets in the Treatment of Patients With Impaired Glucose Tolerance and Mild Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) are growing public health challenges. Early intervention in mild T2DM and IGT is essential to prevent disease progression and severe complications. Traditional Chinese Medicine (TCM) provides a potential therapeutic approach.

Sanggua tablets, a TCM formula composed of mulberry leaf, bitter melon, kudzu root, Chinese yam, and cassia seed, embody TCM principles of clearing heat, generating body fluids, tonifying the spleen and stomach, and nourishing the lungs and kidneys. Modern studies show that Sanggua tablets effectively lower blood glucose and improve lipid profiles through components like mulberry polysaccharides and bitter melon saponins. These findings suggest their potential as an alternative or complementary therapy for mild T2DM and IGT.

This study will conduct a randomized, double-blind, placebo-controlled, parallel-group clinical trial among patients with IGT and mild T2DM. Participants will receive a 16-week intervention with Sanggua tablets. The primary outcome is glycated hemoglobin (HbA1c), with secondary outcomes such as fasting blood glucose (FBG), fasting insulin (FINS), HOMA-IR, lipid profiles and so on. Safety will be closely monitored. Additionally, fecal samples will be collected for 16S rDNA sequencing to explore the role of gut microbiota in the therapeutic effects of Sanggua tablets. This study aims to provide evidence for the clinical application and development of Sanggua tablets as a novel TCM therapy.

Type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) are significant public health concerns, with rising prevalence rates globally. Treating mild T2DM and IGT is crucial to prevent disease progression and reduce the risk of severe complications such as cardiovascular diseases. Traditional Chinese Medicine (TCM) offers a promising approach in this context.

Sanggua tablets, a TCM formula, consist of mulberry leaf, bitter melon, kudzu root, Chinese yam, and cassia seed. These ingredients work synergistically to achieve the TCM therapeutic principles of clearing heat and detoxifying, generating body fluids and moistening dryness, tonifying the spleen and stomach, and nourishing the lungs and kidneys. Modern pharmacological studies have shown that Sanggua tablets have significant therapeutic potential. Their components, such as mulberry polysaccharides and bitter melon saponins, have been proven to lower blood glucose levels by promoting glycogen synthesis and inhibiting glucose absorption. Additionally, they have demonstrated hypolipidemic effects, improving lipid profiles and potentially preventing atherosclerosis.

Clinical and experimental evidence suggests that Sanggua tablets can effectively improve insulin resistance and regulate lipid metabolism. These findings highlight their potential as an alternative or complementary therapy for mild T2DM and IGT. Further research is needed to elucidate their mechanisms of action and optimize their clinical application.

This study proposes to employ a randomized, double-blind, placebo-controlled, parallel-group clinical trial design. The study population will consist of patients with IGT and mild T2DM. Participants will undergo a 16-week intervention with Sanggua tablets. The primary outcome is glycated hemoglobin (HbA1c), with secondary outcomes such as fasting blood glucose (FBG), fasting insulin (FINS), HOMA-IR, lipid profiles and so on. Safety indicators will also be closely monitored. The clinical efficacy of Sanggua tablets will be re-evaluated through these measures. Additionally, to explore its mechanism of action, fecal samples will be collected from participants for 16S rDNA sequencing to investigate the role of gut microbiota. This study aims to provide evidence for the clinical application and potential development of Sang Gua tablets as a Category 1.1 innovative traditional Chinese medicine.

Based on calculations using the PASS 15 software, a total of 84 participants are required for enrollment, with 42 participants in each group.

Initially screened participants will undergo baseline assessments during the screening period (V0, from Day -7 to Day 0) to determine their eligibility based on the inclusion and exclusion criteria. Randomization of eligible participants and the preparation of randomization envelopes will follow the principles of randomized clinical trial design. Participants meeting the inclusion and exclusion criteria will be randomly assigned to two groups in a 1:1 ratio, receiving either conventional treatment plus Sanggua tablets or conventional treatment plus placebo. Both Sanggua tablets and the placebo will be manufactured by Wuhan Jianmin Dapeng Pharmaceutical Co., Ltd. Random numbers generated using SAS software will be used to determine the codes for participants in the two groups. Two copies of the randomization envelopes will be prepared, sealed, and separately stored by the investigator and the person in charge of the clinical study. After 16 weeks of treatment, the efficacy and safety of the interventions will be evaluated.

Study Visits:

V0 (Screening): Conducted 7 days before enrollment, includes assessments such as physical examination, vital signs, fasting blood glucose (FBG), glycated hemoglobin (HbA1c).

V1 (Enrollment): Occurs on Day 0, where participants are assigned to groups and begin treatment.

V2 (4 weeks): Participants are assessed for FBG, vital signs, and other routine checks.

V3 (8 weeks): Participants are assessed for FBG, vital signs, and additional assessments.

V4 (12 weeks): Participants are assessed for FBG and vital signs assessment. V5 (16 weeks): Final assessment includes physical examination, vital signs, FBG, HbA1c, oral glucose tolerance test (OGTT), and other glycemic and lipid profiles.

V6 (Post-study): Follow-up 28 days after the last dose, includes a telephone interview for any adverse events.

Inclusion Criteria:

• Patients aged 18-70 with impaired glucose tolerance (IGT).
• Patients aged 18-70 diagnosed with type 2 diabetes mellitus (T2DM) deemed by the clinician not requiring pharmacological intervention.
• Glycated hemoglobin (HbA1c) levels between 5.6% and 7.5%.
• Voluntarily sign an informed consent form before the commencement of trial-related activities, understand the procedures and methods of the trial, and are willing and able to strictly adhere to the clinical trial protocol to complete the study.

Exclusion Criteria:

• Type 1 diabetes mellitus.
• Known allergies to Sang Gua tablets or any of its components.
• Use of hypoglycemic or lipid-lowering drugs within the last three months.
• Presence of severe primary or secondary respiratory, cardiovascular, hepatic, or renal diseases, rheumatic connective tissue diseases, or hematological disorders.
• Uncontrolled or unstable conditions exacerbated by infections, severe electrolyte imbalances, or other factors.
• Patients with primary or secondary kidney diseases, hypertension, heart failure, acidosis, or urinary tract infections causing increased urinary protein, excepted.
• Patients with psychiatric disorders.
• Pregnant or planning to become pregnant women, or nursing mothers.
• Patients requiring long-term steroid therapy.
• Patients with poorly controlled hypertension or secondary hypertension.
• Patients who have participated in other clinical trials within the past three months.
• Patients deemed by the investigator as unsuitable for this clinical trial due to potential interference with trial results, impediments to full participation in the study, medical history, disease evidence, abnormal treatments, or laboratory values, or any other condition considered by the investigator to pose potential risks for participation in the study.