RCT of a Polyherbal Dietary Supplement for Prediabetes

Prediabetes is a common state in which blood glucose levels are elevated, but are not
elevated high enough to be considered Type 2 Diabetes (T2D). The worldwide prevalence of
prediabetes is high and rapidly increasing. People with prediabetes are at increased risk for
developing a variety of chronic diseases. Most notably, prediabetes nearly always precedes
diagnosis of T2D, a poorly-controlled disease adversely affecting 14% of adults in the United
States. T2D is responsible for increased risk of heart disease, stroke, blindness and other
vision problems, kidney disease, amputations and death. Prediabetes often progresses to T2D
relatively quickly, as pancreatic beta-cell dysfunction perpetuates. There are currently
limited pharmacological options available for safely reducing the burden of prediabetes.
Furthermore, these pharmacological options often carry potentially deleterious side effects.
Low-risk alternatives are needed where lifestyle modifications, such as increased physical
activity and weight loss, have failed.

Herbal dietary supplements have shown promise in safely managing impaired glycemic control in
prediabetic adults in many clinical studies. A wide variety of herbs have been previously
studied for these purposes, including cinnamon, fenugreek, banaba, curcumin, and a variety of
combination products. Of these, most have demonstrated improved management of glycemic
control, particularly with regard to reducing fasting blood glucose and postprandial glucose,
HbA1c, fasting insulin levels, HOMA-Insulin Resistance, and increasing HOMA-β cell function
among prediabetic adult populations. Many herbs have also demonstrated benefit in the
management of glycemic control in clinical trials among T2D populations. These herbs include
berberine, ginseng, gymnema, banaba, cinnamon, fenugreek, and kudzu, all of which are present
in GlucoSupreme™ Herbal.

The research team hypothesizes that GlucoSupreme™ Herbal will demonstrate superior
improvements in markers of glycemic control than placebo over twelve weeks of daily
supplementation among a sample of healthy adults. The research team aims to conduct a
randomized, placebo-controlled, double-blinded clinical trial to evaluate this hypothesis
among a diverse sample of 40 prediabetic adults, and will implement a 1:1 study allocation
ratio. This study will utilize an adaptive sample size re-estimation (SSR) approach where
participant enrollment may be extended beyond the originally planned sample size if interim
effect size is smaller than anticipated, but still promising, thereby preserving study power;
this will be determined by examination of available unblinded endpoint data by an independent
statistician after 30 subjects are enrolled.

Inclusion Criteria:

1. Age ≥ 18 years

2. Prediabetic blood measurement (HbA1C) of 5.7-6.4% and/or fasting blood glucose of
100-125 mg/dl and/or 2-hour Oral Glucose Tolerance Test blood glucose value of 140
mg/dl-199 mg/dl1 2) taken within the last 12 weeks

3. Agree to continue with current diet and refrain from taking any new nutritional or
herbal supplements

4. Able to understand and write English

5. Voluntarily consent to the study and understand its nature and purpose including
potential risks and side effects

Exclusion Criteria:

1. Current daily use of any oral hypoglycemic medication or insulin injection

2. Current daily use of any supplement containing the herbs in the study supplement

3. Known allergies to any substance in the study supplement

4. Current daily tobacco smoker

5. Currently pregnant or planning to become pregnant in the next 12 weeks

6. Any current or previous diagnosis of diabetes (Type 1 or Type 2)

7. Myocardial infarction, vascular surgery, or stroke in the past year