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[DOI] [PMC free article] [PubMed] [Google Scholar] 130.Sowmya PR, Arathi BP, Vijay K, Baskaran V, Lakshminarayana R

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Berberine Berberine—an isoquinoline alkaloid isolated from herbs such as Oregon grape and goldenseal—has demonstrated insulin-sensitizing effects comparable to metformin.[7][24] In a three-month RCT of 89 women with PMOS and insulin resistance, berberine (500 mg TID) reduced waist circumference, waist-to-hip ratio, total cholesterol, triglycerides, and LDL cholesterol compared with metformin, while also increasing HDL cholesterol and SHBG.[7] A systematic review and meta-analysis of 12 RCTs found that berberine significantly decreased total testosterone and the LH/FSH ratio compared with placebo, and improved waist circumference, waist-to-hip ratio, and total cholesterol compared with metformin.[25] A meta-analysis of 9 RCTs in PMOS patients with insulin resistance found no significant difference between berberine and metformin in alleviating insulin resistance, improving glycolipid metabolism, or improving reproductive endocrine parameters—suggesting comparable efficacy.[24] A retrospective study found that adjunctive berberine therapy significantly reduced fasting insulin, fasting blood sugar, HOMA-IR, total testosterone, and inflammatory markers (CRP, TNF-α, IL-6) in women with PMOS.[26] Berberine also has potential benefits for nonalcoholic steatohepatitis—a common long-term complication of PMOS—through its effects on liver fat, triglycerides, and liver enzymes.[27] Importantly, berberine did not increase the incidence of gastrointestinal adverse events compared with placebo in pooled analyses, which may represent an advantage over metformin for some patients.[25] N-Acetyl-Cysteine (NAC) NAC is an antioxidant that functions as both an insulin sensitizer and anti-inflammatory agent