Huangqi Gegen Decoction for Endothelial Function in Type 2 Diabetes at Very High ASCVD Risk

This is a single-center, randomized, double-blind, placebo-controlled clinical trial conducted at Putuo Hospital, Shanghai University of Traditional Chinese Medicine.

Eligible participants are adults aged 18 to 75 years with type 2 diabetes mellitus, very high risk of atherosclerotic cardiovascular disease, and Qi-Yin deficiency syndrome according to traditional Chinese medicine criteria. Participants are randomly assigned in a 1:1 ratio to the experimental group or the placebo control group.

Both groups continue stable conventional treatment for diabetes and cardiovascular risk management. The experimental group receives Huangqi Gegen Decoction granules in addition to conventional treatment, while the control group receives matching placebo granules in addition to conventional treatment. The intervention period is 12 weeks. The study medication and placebo are designed to have similar appearance, packaging, and administration, and participants and investigators remain blinded to treatment assignment.

Participants are assessed at baseline and followed during the 12-week treatment period. Flow-mediated dilation is assessed as the primary measure of endothelial function. Additional assessments include glucose metabolism, biomarkers related to endothelial function and inflammation, traditional Chinese medicine syndrome scores, and safety outcomes. Adverse events and concomitant medications are monitored throughout the study.

The study is designed to determine whether adding Huangqi Gegen Decoction to conventional treatment provides additional improvement in endothelial function and related clinical measures compared with conventional treatment plus placebo.

Inclusion criteria

• Aged 18 to 75 years.
• Diagnosed with type 2 diabetes mellitus, with fasting plasma glucose <9.0 mmol/L and glycated hemoglobin (HbA1c) <8.5%, and receiving a stable glucose-lowering treatment regimen without adjustment during the previous 3 months.
• Type 2 diabetes mellitus with target-organ damage or at least 3 additional cardiovascular risk factors.
• Meets the diagnostic criteria for Qi-Yin deficiency syndrome in traditional Chinese medicine, including: (a) primary symptoms of dry mouth and thirst, palpitations, and shortness of breath; (b) secondary symptoms including spontaneous sweating, fatigue, chest tightness, chest discomfort or pain, heat sensation in the palms and soles, polyuria, or constipation; and (c) dark-red tongue and weak, thready pulse. The diagnosis requires at least 2 primary symptoms together with supporting secondary symptoms and tongue/pulse findings, and must be confirmed by at least 2 traditional Chinese medicine physicians at attending-physician level or above.
• Voluntarily participates in the study and provides written informed consent.
• Has received stable conventional treatment for at least 3 months before enrollment, with the treatment regimen consistent with relevant Chinese clinical guidelines for diabetes and chronic coronary syndromes.

Exclusion criteria

• Allergy to the traditional Chinese medicines used in the study or a history of multiple drug allergies.
• History of severe arrhythmia, including recurrent or symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response, or New York Heart Association (NYHA) functional class III-IV heart failure.
• Abnormal thyroid function, including hyperthyroidism or hypothyroidism, defined as thyroid-stimulating hormone below the lower limit of normal or greater than 1.5 times the upper limit of normal.
• History of malignant tumor within the previous 5 years.
• Major surgery within the previous 3 months or planned major surgery during the study period.
• Long-term or repeated use of systemic glucocorticoids within the previous 3 months.
• Active infectious disease at screening or randomization, psychiatric illness, pregnancy or breastfeeding, or any other condition considered by the investigator to make participation inappropriate.
• Current use of other medications that may significantly affect systemic immune function.
• Acute infection or an active inflammatory condition, such as a respiratory tract infection or recent surgery.
• Hematologic disorders that may affect immune or inflammatory markers, including chronic myeloid leukemia, idiopathic thrombocytopenic purpura, or aplastic anemia.
• Current use of long-acting nitrates or other medications that may affect vasodilatory function.
• Use of other traditional Chinese medicine preparations or dietary supplements with known anti-inflammatory or antioxidant effects, such as curcumin or coenzyme Q10, within 1 month before screening.