The incidence of liver disease, including hepatitis and hepatic cirrhosis, as a result of the administration of antidiabetic medications is approximately 0.1-0.5%. From Mar. 1996-Aug. 2000, He Yong-he et al. studied the effects of a particular Chinese medicinal formula on 72 patients with liver disease due to antidiabetic drugs. The results of this study were published in issue #12, 2001 of the Zhong Yi Za Zhi (Journal of Chinese Medicine) on pages 724-726. Because this study suggests that Chinese medicinals may eliminate such liver disease while still continuing to take the antidiabetic medications, a summary of this study appears below.
Cohort description:
Altogether, 129 patients were included in this study, all of whom met the WHO criteria for diabetes mellitus and all of whom had varying degrees of liver damage. None of these patients had had any history of liver or kidney dysfunction prior to taking antidiabetic medications, and all met 1989 criteria for medication induced liver disease, including changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (GGT), bilirubin (BIL), blood urea nitrogen (BUN), total protein (TP), albumin (ALB), and prothrombin time (PT). Chinese medical diagnosis was based on criteria published in the 1995 Zhong Yi Bing Zheng Zhen Duan Zhi Xiao Biao Sun (Criteria for the Chinese Medical Diagnosis of Diseases & Patterns and Treatment Efficacy).
The total of 129 patients was divided into two groups, a treatment group of 72 patients and a comparison group of 57 patients. In the treatment group, there were 45 males and 27 females aged 23-76, with a median age of 52.9 ± 8.3 years. These patients had a disease duration of 3-28 years. In nine case, there was accompanying cerebral infarction, 26 cases had nephropathy, 22 cases had eye disease, 32 cases had peripheral neuritis, 27 cases had hypertension, 29 cases had high cholesterol, and four cases had diabetic bladder disease. Sixty-five of these patients were on oral antidiabetic medications, and seven were on insulin. In the comparison group, there were 33 males and 24 females aged 21-77 years old, with a median age of 57.4 ± 6.8 years. These patients had been ill for 5-31 years. Six of these cases had accompanying cerebral infarction, 15 had nephropathy, 12 had eye disease, 19 had peripheral neuritis, 10 had diabetic foot, and 26 had high cholesterol. Fifty-three of these patients were on oral antidiabetic medications, and four were on insulin. Therefore, in terms of sex, age, disease duration, diabetic complications, and medication, there were no marked statistical differences between these two groups.
In terms of percentages of antidiabetic medications used by members of both these two groups, 73.65% were on sulfonylurea-type medications, 51.83% were on biguanide-type medications, 19.37% were on alpha-glucosidase inhibitors, and 2.27% were on insulin.
Treatment method:
Both groups continued taking their antidiabetic medications without any changes. In addition, the treatment group was administered a Chinese medical formula named Hua Tan Yi Gan Tang (Transform Phlegm & Boost the Liver Decoction) which was composed of: Pericarpium Citri Reticulatae Viride (Qing Pi), 25g, Radix Peucedani (Qian Hu), 12g, Sclerotium Poriae Cocos (Fu Ling), 15g, Flos Inulae Racemosae (Xuan Fu Hua), 12g, Rhizoma Cyperi Rotundi (Xiang Fu), 15g, Radix Bupleuri (Chai Hu), 20g, cooked Radix Et Rhizoma Rhei (Da Huang), 10g, Radix Albus Paeoniae Lactiflorae (Bai Shao), 15g, Radix Codonopsitis Pilosulae (Dang Shen), 10g, and Fructus Schisandrae Chinensis (Wu Wei Zi), 8g. If lack of strength was severe, 15 grams of mix-fried Radix Astragali Membranacei (Huang Qi) were added. If abdominal distention was severe, 10 grams of Pericarpium Arecae Catechu (Da Fu Pi) and 12 grams of Radix Auklandiae Lappae (Mu Xiang) were added. If torpid intake was severe, 10 grams of Herba Eupatorii Fortunei (Pei Lan), 20 grams of stir-fried Fructus Germinatus Hordei Vulgaris (Mai Ya), and 12 grams of Rhizoma Atractylodis Macrocephalae (Bai Zhu) were added. If nausea was severe, 12 grams of Rhizoma Pinelliae Ternatae (Ban Xia) and 15 grams of Caulis Bambusae In Taeniis (Zhu Ru) were added. If oral dryness and a bitter taste were severe, 12 grams of Herba Dendrobii (Shi Hu) and 15 grams of Radix Trichosanthis Kirlowii (Tian Hua Fen) were added. If fever was severe, 15 grams of Herba Oldenlandiae Diffusae Cum Radice (Bai Hua She She Cao) and 15 grams of Herba Patriniae Heterophyllae Cum Radice (Bai Jiang Cao) were added. If jaundice was severe, 20 grams of Herba Artemisiae Capillaris (Yin Chen Hao), 10 grams of Rhizoma Coptidis Chinensis (Huang Lian), and 12 grams of Fructus Gardeniae Jasminoidis (Zhi Zi) were added. If loose stools were severe, 12 grams of Rhizoma Atractylodis (Cang Zhu) and 10 grams of Cortex Magnoliae Officinalis (Hou Po) were added. One ji of these medicinals were boiled in 600ml of water down to 200ml each day and administered in two divided doses, morning and evening 15 minutes after eating.
Those patients in the comparison group received 0.1g of vitamin C, 100mg of vitamin E, and 0.2g each of of compound vitamin B1 and glucuronolactone three times per day. Ten days equaled one course of treatment, and three courses were administered.
Treatment outcomes:
Basic cure was defined as healing of the clinical symptoms, all laboratory analyses returning to normal, liver function returning to normal, and no recurrence on follow-up after a half year. Some effect was defined as either healing or marked improvement in the clinical symptoms, normalization of all laboratory analyses, liver function returning to normal, but some abnormality in at least one of the above criteria within one half year on follow-up. No effect meant that there was no marked change in clinical symptoms, liver function was still abnormal, or the disease had actually gotten worse.
Based on the above criteria, in the treatment group, 40 cases (55.56%) were judged basically cured, 28 cases (38.89%) got some effect, and four cases (5.55%) got no effect. Thus the total amelioration rate was 94.45% in the treatment group. In the comparison group, 21 cases (36.84%) were judged basically cured, 27 cases (47.36%) got some effect, and nine cases (15.8%) got no effect, for a total amelioration rate of 84.20%. Hence there was a marked statistical difference in cure rate (P + 0.01) and total amelioration rate (P + 0.05) between these two groups, with the Chinese medical protocol being judged more effective than the Western medical protocol. In terms of liver function and BUN, there was a marked difference between the treatment and comparison groups (P + 0.01), but there was no marked change in PT. In addition, there were no adverse reactions in the treatment group.
According to the Chinese authors of this study, liver disease as a result of antidiabetic medications should be categorized in Chinese medicine as accumulations and gatherings (ji ju), jaundice (huang dan), and liver qi depression (gan qi yu). Diabetes itself is mostly due to yin vacuity with dryness and heat. On top of this, oral antidiabetic medications enter the stomach and may make the spleen and stomach vacuous as well. In that case, the spleen may not upbear the clear and downbear the turbid. If turbidity endures, over time it gathers into dampness and transforms into phlegm. Then a combination of phlegm and stasis cause the spleen movement and transformation even further loss of fortification and the liver-gallbladder’s coursing and discharge loose their duty. Therefore, there appears spleen stagnation and liver depression. If these evils are not diffused and discharged, eventually liver woods loses its nourishment and liver blood becomes insufficient. Thus the authors believe that the main disease mechanisms of this condition are phlegm and blood stasis and stagnation and hence they also think that the treatment principles for dealing with this condition should be to move the qi and transform phlegm, boost the liver, disinhibit the gallbladder, and fortify the spleen.
Based on these theoretical considerations, within the formula used in this protocol, Qing Pi disperses phlegm, disinhibits the qi, and breaks stagnation at the same time as it harmonizes the center and courses the liver. It enters the liver where it scatters evils and it enters the spleen where it eliminates phlegm. It levels the lower burner liver qi and guides the other medicinals to enter the jue yin aspect or division. Qian Hu transforms and downbears phlegm located in the liver. Fu Ling fortifies the spleen, eliminates dampness, and disperses phlegm accumulation. Xuan Fu Hua descends the qi and disperses phlegm, scatters and frees the flow of static blood. Xiang Fu enters the liver and gallbladder channels where it resolves qi depression and dispels stasis. Chai Hu drains phlegm nodulation from the liver-gallbladder and scatters blood congelation and qi gathering in all the other channels. It assists Xiang Fu to open depression and course the liver. Cooked Da Huang flushes phlegm and cleanses static blood. Thus it regulates the center by eliminating the old so that the new can be engendered. Bai Shao both upbears and downbears. It is able to drain and it is able to scatter. However, it is also able to supplement and restrain. It is able to drain wood from center earth. When stir-fried, it disinhibits the qi of the liver-gallbladder. When combined with Xiang Fu and Chai Hu, it resolves depression. Wu Wei Zi restrains lung metal so as to level liver wood. It also protects kidney water so that it can enrich liver wood. Dang Shen fills and regulates the qi and blood of the viscera and bowels, thus aiding the function of all the other medicinals. Therefore, when all these medicinals are used together, the qi and blood are moved and regulated, phlegm is dispelled and depression is resolved, the liver is boosted, the gallbladder is disinhibited, and the spleen is fortified. Thus the viscera and bowels all become quiet.