Reference
Ji H, Zhao X, Chen X, et al. Jinlida for diabetes prevention in impaired glucose tolerance and multiple metabolic abnormalities: the FOCUS randomized clinical trial. JAMA Intern Med. 2024;184(7):727-735.
Study Objective
To evaluate the effect of long-term administration of Jinlida, a Traditional Chinese Medicine (TCM) herbal formula found primarily in China, vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities
Key Takeaway
Use of the TCM herbal formula Jinlida (JLD) shows significant promise in preventing the onset of diabetes in Chinese individuals diagnosed with multiple metabolic disorders. Additionally, preliminary findings suggest potential for JLD as an asset in the management of diabetes for those already diagnosed.
Design
This was a multicenter, double-blind, placebo-controlled, randomized clinical trial deployed through 35 clinics in 21 cities in China from June 2019 to February 2023.
Participants
Participants included 422 men and 463 women aged 18 to 70 years with glucose impairment and metabolic abnormalities including abdominal obesity measured by waist circumference. The mean age of participants was 52.6 years. Participants were randomly divided into 2 groups (1:1 ratio), with 442 receiving the Jinlida granules and 443 receiving placebo.
Intervention
All participants received 9 g of JLD granules orally 3 times per day or the placebo, which was matched to the JLD granules in weight, color, shape, odor, taste, texture, packaging, specifications, and labeling. The article did not list specific ingredients for the placebo. Participants continued the protocol for the duration of the study or until they developed diabetes, withdrew from the study, were lost to follow-up, or died.
Study Parameters Assessed
During the 1-month induction period and throughout the study, all participants received lifestyle intervention guidance including recommendations for daily habits, regular physical activity, and dietary changes. Participants were visited monthly for examinations and tests and had individualized guidance throughout the program to evaluate adherence to lifestyle adjustments. Every quarter, participants received an oral glucose tolerance test, capillary blood glucose monitoring, and monthly glucometer readings.
Researchers followed the Consolidated Standards of Reporting Trials (CONSORT) Extension for Chinese Herbal Medicine Formulas 2017 reporting guidelines.
Primary Outcome
Primary outcome was diabetes onset. Secondary outcomes included
- impacts to waist circumference;
- fasting and 2-hour postprandial plasma glucose levels;
- HbA1c;
- fasting insulin level;
- homeostatic model assessment for insulin resistance (HOMA-IR);
- total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels;
- ankle-brachial index; and
- carotid intima-media thickness (CIMT).
Individuals were excluded for history of type 1 or type 2 diabetes, hypo- or hyperthyroidism, uncontrolled hypo- or hypertension, use of hypoglycemic drugs within 90 days, significant liver or kidney dysfunction, or other serious organ diseases, pregnancy, or breastfeeding.
Key Findings
Results indicate that use of JLD can significantly reduce the risk of developing diabetes in individuals with metabolic abnormalities and IGT over the median follow-up duration of 2.2 years (27.83% of the JLD group vs 42.66% of the placebo group). Individuals in the JLD group had lower incidence of diabetes when matched by age, sex, waist circumference, history of hyperlipidemia and hypertension, HbA1c, triglyceride and high-density lipoprotein cholesterol (HDL-C) levels, CIMT, and metabolic syndrome components.
Those receiving JLD experienced greater reduction in waist circumference (2.31 cm vs 1.36 cm) and body mass index (0.41 vs 0.14), as well as greater improvement in HBA1c and blood glucose levels, as compared to those who received placebo. Improvements in blood parameters with JLD granules over placebo also occurred with lipid profiles, where total-cholesterol reduction was more than double in the JLD group than in the placebo group.
The article reports that almost 95% of the JLD group and 92% of the placebo group reported adverse events but with only 4 per group withdrawing as a result. Seventy-one participants from the JLD group and 56 from the placebo group were diagnosed with coronavirus infections during the study. Twenty individuals from the JLD group and 18 from the placebo group reported serious adverse events (not identified).
About 44.5% of JLD and about 44.6% of placebo participants experienced gastrointestinal disorders, the most reported adverse event, with approximately 15.6% of JLD and 16.6% of placebo participants reporting diarrhea. Nasopharyngitis was the second-most-reported adverse event (~30.7% of the JLD group and ~29.8% of the placebo group), followed by cough (~32.3% of the JLD group and ~29.2% of the placebo group) and dizziness (~23.3% of the JLD group and ~24.2% of the placebo group). Almost 19% of the JLD group and 17% of the placebo group reported headaches. Of note, approximately 8.4% of the JLD group and approximately 7.2% of the placebo group experienced hepatic disorders, and about 6.3% of the JLD group and about 4.5% of the placebo group experienced cardiovascular events. No correlation was made to any of these events (or others) for participants who reported coronavirus infection during the study.
Transparency
The article provided author affiliations and included notice of funding, support, and a conflict of interest reported by 1 of the study investigators.
Practice Implications & Limitations
Notably, this study took place during Covid-19 pandemic restrictions in China, and the authors make no mention of how that may have affected participants' health in terms of the adverse events. At this time, the Jinlida formula is not a standard formula used in the United States. Ingredients of the formula, however, are well-known and trusted in the TCM herbal community; they are part of the standard education and practice of all TCM herbal practitioners. In general, the herbs address TCM diagnostic patterns pointing toward organ systems, including lung, spleen, kidney, and stomach, as well as, to a lesser degree, urinary bladder, small intestines, and heart systems.
The article reports that almost 95% of the JLD group and 92% of the placebo group reported adverse events but with only 4 per group withdrawing as a result.
In TCM, these are the primary organ systems responsible for metabolic function in terms of transformation, digestion, and absorption of essential elements throughout the body’s tissues. The actions of the herbs include tonifying qi, clearing heat, drying dampness, and regulating/invigorating blood. Although we know the ingredients of the JLD formula, the article does not list the percentages of those ingredients in the formula. Using Western methods, researchers have studied some of the herbs individually, but historical writings and 3,000-plus years of empirical evidence are difficult to measure by Western standards. The strength of the Chinese formulary, as practiced for millennia, is in providing an herbal prescription to synergistically balance individuals’ qualities and deliver a medicinal impact. References and citations within the article point to research describing the chemical composition of herbs within this formula, so readers can review the information separately.
In a 2015 article published in PLoS/One, researchers introduced Jinlida to a smaller cohort of 186 patients diagnosed with diabetes, through a double-blind, randomized, placebo-controlled, multicenter trial that used Jinlida as an adjunctive to metformin. Conducted over 12 consecutive weeks, the study aimed to determine whether the herbal formula would enhance glycemic control in type 2 diabetes patients. The results of that study showed significant reduction in HbA1c for the Jinlida group vs placebo.1
In 2017, Diabetes Therapy published a systematic review of 6 trials, with a total of 1,027 participants, investigating the effect of the Chinese herbal medicine Tianqi on preventing type 2 diabetes. Tianqi is an herbal formula found in the United States. The review found that Tianqi capsules helped normalize glucose levels and slow progression to type 2 diabetes.2 The Jinlida and Tianqi formulas have 4 herbs in common, but the Jinlida formula is more robust overall.
Investigators in this study followed the CONSORT Extension for Chinese Herbal Medicine Formulas 2017. As such, this is an important milestone as research on Chinese herbal medicine has lagged behind that performed on Western pharmaceuticals and supplements due to lack of standardized measures.3
Conflict of Interest Disclosure
The author declares no conflict of interest.
