Glucose transporter 4 mRNA expression in subcutaneous adipose tissue of women with PCOS remains unchanged despite metformin withdrawal: is there a cellular metabolic treatment legacy effect?

Purpose: Metformin induces GLUT-4 mRNA expression in insulin target tissues in PCOS. It is unclear how long this impact is sustained after withdrawal of metformin. We aimed to compare the effect of metformin withdrawal on GLUT-4 mRNA expression in subcutaneous adipose tissue after prior short (ST, 1 year, N = 11) and long term (LT, at least 3 years, N = 13) treatment in obese PCOS women. Methods: At baseline and 6 months after withdrawal, biopsy of subcutaneous adipose tissue followed by quantitative PCR analysis was performed to determine GLUT-4 mRNA expression. Results: We found no time/effect differences in GLUT-4 mRNA expression in ST (2-dCt at baseline 0.42 (0.16–0.48) vs 2-dCt after 6 months 0.31 (0.22–0.56), p = 0.594) and no time/effect difference in LT group (2-dCt at baseline 0.24 (0.14–0.39) vs 2-dCt after 6 months 0.25 (0.20–0.38), p = 0.382). There was also no difference in GLUT-4 mRNA expression between both groups at baseline and after 6 months. Conclusions: In summary, 6 months after metformin withdrawal, GLUT-4 mRNA expression in subcutaneous adipose tissue remained stable, regardless of the prior treatment duration.