Endocrine Abstracts

Introduction: Silymarin is a standardized extract of the milk thistle (Sylibum marianum) seeds, containing a mixture of flavonolignans: silybinin, isosilybinin, silycristin, silydianin, and others. It is used in the treatment of toxic liver damage and as adjunctive therapy in chronic hepatitis and cirrhosis. Recent studies have shown a potential benefit in the treatment of diabetes mellitus and non-alcoholic fatty liver disease. We undertook to study the effect of silymarin on insulin sensitivity in prediabetic patients with preclinical liver disease.

Methods: For this open, uncontrolled trial, patients 18–75 years old of both sexes with prediabetes and moderately elevated transaminases or GGT (<3 × ULN) were assigned for treatment twice a day for 3 months with a capsule containing silymarin (196 mg) plus Agrimonia eupatoria extract (166 mg) plus Lamium album extract (166 mg). The main endpoint was the change in the HOMA-2 index of insulin resistance (https://dtu.ox.ac.uk/homacalculator). Secondary endpoints: effects on fasting glucose, insulin, HbA_1C, and the change of status from prediabetes to normoglycemia or diabetes mellitus. Tertiary endpoints: changes in AST, ALT and GGT. Additional endpoints: changes in BMI, lipid profile, blood pressure and heart rate. Security endpoints: Reported adverse effects and compliance (by questionnaire).

Results: 11 patients were recruited (64% women, age 49.3 ± 12.3 years, BMI 32.2 ± 6.3 kg/m²). The HOMA-2 index was significantly reduced from 3.49 ± 0.58 to 2.96 ± 0.49 (P = 0.043, paired t-test). Fasting insulin, but not fasting glucose or HbA_1C, was also significantly reduced. 2 patients changed status to normoglycemia but none progressed to diabetes mellitus. AST, ALT and GGT were significantly reduced. BMI, lipid profile, blood pressure and heart rate did not change significantly, but there was a trend for reduced triglycerides and increased HDL-cholesterol. The mean reported compliance was 87% and no serious side effects were reported; no patient withdrew from the study.

Conclusions: The combined extracts of Silybum marianum, Agrimonia eupatoria and Lamium album were well tolerated and able to ameliorate the insulin resistance of prediabetic patients with preclinical liver damage, mainly by decreasing their fasting insulin. The liver enzyme profile was also improved. This combination could be expected to reduce the long term risk of progression to type 2 diabetes in these patients. The limitations of this pilot trial are obvious, but a full-scale trial seems warranted.