Re: Ginkgo Extract Improves Blood Glucose Levels, HbA1c, and Other Biomarkers in Patients Taking Metformin for Type 2 Diabetes

Ginkgo (Ginkgo biloba, Ginkgoaceae) Diabetes Mellitus Metformin Date: 09-14-2018 HC# 081811-600 Aziz TA, Hussain SA, Mahwi TO, Ahmed ZA, Rahman HS, Rasedee A. The efficacy and safety of Ginkgo biloba extract as an adjuvant in type 2 diabetes mellitus patients ineffectively managed with metformin: a double-blind, randomized, placebo-controlled trial. Drug Des Devel Ther. April 5, 2018;12:735-742. doi: 10.2147/DDDT.S157113. Diabetes mellitus (DM) is a metabolic disorder characterized by chronic elevations in blood glucose, abnormal carbohydrate metabolism, and other metabolic abnormalities resulting from insulin resistance, as is the case in early stages of type 2 diabetes mellitus (T2DM), or inadequate insulin levels. Many pharmaceutical drugs lower blood glucose, but they may have significant side effects and limited effect on long-term outcomes. Ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract (GKB extract) is reported to have multiple beneficial bioactivities, including antioxidant, anti-inflammatory, neuroprotective, and cardioprotective activities, among others. GKB extract has been used to treat arteriosclerosis, abnormal blood clotting, ischemic heart disease, and hypertension, and recently as a putative preventive for T2DM. It is a relatively inexpensive intervention. This study determined the effect of GKB extract as an adjuvant to metformin (Met) for the treatment of T2DM. Met tablets for the study were obtained from a pharmacy. A powdered GKB extract was obtained from Apollo Healthcare Resources (West Coast Vista, Singapore). [Note: the publication identified this product as EGb761, but it has been determined that it was not the Schwabe product of that name, and no further information on content was given.] Placebo tablets were specially manufactured locally. The study was a randomized, placebo-controlled, double-blinded, multicenter clinical trial. It took place between December 2016 and October 2017 at the Center of Diabetes and Endocrine Glands in Sulaimani City, Iraq. Patients were recruited from nearby hospitals and clinics. Eligible patients were males or females, aged between 25 and 65 years, diagnosed with T2DM at least one year prior to the study, and with blood glucose levels inadequately controlled by Met alone. Exclusion criteria included pregnancy; type 1 DM, ischemic heart disease, cardiac arrhythmias, glucose-6-phosphate dehydrogenase deficiency, bleeding disorders, or seizures; known hypersensitivity to GKB extract, Met, or placebo; and use of supplements containing multivitamins or polyphenols. Of the 80 screened, 60 people were found eligible for the study and randomized into two groups of 30 each. The placebo group received a 120 mg starch capsule per day in addition to their usual Met dose (1.24±0.67 g/day). The GKB group received 120 mg capsule GKB extract per day in addition to Met (1.36±0.45 g/day). Treatment lasted 90 days, with monthly follow-up appointments. Twenty patients in the placebo group and 27 in the GKB group completed the study. At the beginning and end of the 90-day intervention, researchers collected the following data: body weight, waist circumference (WC), and body mass index (BMI); HbA1c level, hemoglobin (Hb) concentration, hematocrit, red blood cell count, and white blood cell count; serum levels of fasting serum glucose (FSG), insulin, triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), urea, and creatine; aspartate transaminase, alanine aminotransferase, and alkaline phosphatase; and visceral adiposity index (VAI) and insulin resistance index (IRI). Statistical analysis found no significant differences (P>0.05) between the two groups at baseline. The GKB group fared significantly better than the placebo group on almost every measure. Mean HbA1c, which provides an estimate of long-term blood sugar level, declined significantly in the GKB group (from 8.6%±1.6% at baseline to 7.7%±1.2% at the end of the study; P<0.001), while the decrease seen in the placebo group (from 8.8%±2.3% to 8.4%±2.1%) was not significant. FSG similarly declined significantly in the GKB group (from 194.4±66.1 mg/dL at baseline to 154.7±36.1 mg/dL at study end; P<0.001), while there was no significant change in the control group. Changes in serum insulin level and IRI were, however, not significant. BMI declined significantly after the intervention for the GKB group (from 34.0±6.0 kg/m2 to 31.6±5.1 kg/m2; P<0.001). BMI remained unchanged for the placebo group. The same was true for VAI, which fell significantly (P<0.007) after 90 days of treatment for the GKB group (192.0±86.2 to 158.9±67.2) and was unchanged for the placebo group. WC followed a similar pattern. The only significant difference in liver enzyme activity (P<0.05) was a reduction in serum ALP in the GKB group. Urea and creatine levels decreased significantly in the GKB group, while creatine levels increased significantly in the placebo group. The GKB group had significant increases in Hb concentration, hematocrit, and red blood cell count, while the placebo group did not; however, these changes were modest and of uncertain clinical significance. The white blood cell count did not change in either group. The platelet count declined significantly in the placebo group after the intervention. Uncontrolled hyperglycemia leads to various long- and short-term complications, including early death, in people with T2DM. These include vascular rigidity, nephropathy and retinopathy, and peripheral neuropathy. Met improves glycemic control, but frequently causes adverse effects, including weight gain. GKB contains several constituents that suggest its usefulness as an adjunct to Met. There are several biochemical mechanisms that are likely at work. The researchers suggest that it is GKB extract's stimulatory effect on lipolysis that accounts for its effects on BMI, WC, and VAI. The results show that this GKB extract is promising for improving glycemic control in T2DM and preventing the weight gain associated with use of Met. However, since the authors did not provide information regarding the supplement, there is no way to reproduce this trial. The authors report no conflicts of interest. –Anne Louise Merrill