Long-term efficacy of metformin in overweight-obese PCOS: longitudinal follow-up of retrospective cohort

Abstract

Objective Long-term efficacy of metformin in polycystic ovarian syndrome (PCOS) apart from in those with impaired glucose tolerance or diabetes remains unproven. We aimed to evaluate the impact of metformin in overweight-obese patients with PCOS and normal baseline glycemic homeostasis. Methods A 10-year longitudinal follow-up of a retrospective cohort comprising 159 patients with PCOS defined by Rotterdam criteria, BMI ≥25 kg/m2 and normal initial glucose homeostasis (age 28.4 ± 6.4 years, BMI 34.9 ± 6.6 kg/m2) that had been receiving metformin 1000 mg BID. Collection data contained 6085 time-points including anthropometric, hormonal and metabolic parameters. Results After the first year body mass (BM) decreased for 3.9 ± 6.8 kg (P < 0.001) and remained stable during the following 3 years. Menstrual frequency (MF) increased to 3.0 ± 3.9 bleeds/year (P < 0.001) after first year to over 11 bleeds/year in the following years. The total testosterone and androstenedione decreased to 15.4 ± 47.9% and 11.3 ± 46.4% within first year, with further decrease in total testosterone and androstenedione to 37.8 ± 61.8 and 24.8 ± 40.5% at the fifth year of the follow-up. The total conversion rate to prediabetes and diabetes was extremely low throughout observation period. Less than 25% of patients continued with metformin for more than 5 years with further dropout to only 6% on metformin therapy at the tenth year of follow-up. Conclusions Long-term metformin treatment of overweight-obese women with PCOS and normal baseline glycemic homeostasis resulted in reduction and stabilization of BM, improvements of MF and androgen profile and low conversion rate to diabetes.

Effects of metformin withdrawal after long and short term treatment in PCOS: observational longitudinal study

“…DPPRG also showed that metformin- related weight loss sustained over 9 years [ 6 ]. Similar results were retrospectively observed also in PCOS cohort followed for 10 years, with the greatest 3.7% weight reduction after the first year of metformin treatment and sustainable effect up to 10 years in participants that remained adherent to the treatment [ 13 ]. However, the real-word adherence and persistence with long term metformin treatment in women with PCOS is very low.…”

“…However, the real-word adherence and persistence with long term metformin treatment in women with PCOS is very low. The longest retrospective analysis of real-life cohort reported that the drop-out rates increased from about 10% in the first year, 35% in the second year, 50% in the third year, 65% in the fourth and up to 80% in the fifth year of metformin treatment [ 13 ]. Although poor compliance with LT treatment with metformin in PCOS is typically observed in everyday clinical practice [ 21 ], the consequences of withdrawal still remains unexplored.…”

“…Prior to inclusion, short-term (ST) group had been treated with metformin for 1 year (1.03 ± 0.13 years), long-term (LT) group continuously for at least 3 years (5.07 ± 2.52 years). The rationale behind selecting the treatment time in ST and LT groups was based on previous observations that the most meaningful effect of metformin has been demonstrated within first year of treatment, while during the following years of treatment the improved outcomes remained stable [ 13 ]. Out of 250 patients treated with metformin after a year at the outpatients Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, 77 were eligible for enrolment into ST group, 23 agreed to participate.…”

“…Furthermore, long-term treatment with metformin-diet appers to be antiatherogenic by virtue of reductions of LDL-C and increments in HDL-C. The longest 10 year-retrospective study demonstrated that metformin treatment of overweight-obese women with PCOS resulted in reduction and stabilization of weight, improvements of menstrual function and androgen profile and in low conversion rate to diabetes [ 13 ]. However, less than 25% of patients remained adherent to metformin for more than 5 years with further dropout to only 6% of those still adherent to metformin at the 10th year of follow up [ 13 ].…”

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

“…Metformin is a member of the biguanide family with proven safety and efficacy. Metformin has long been used in the management of T2DM and it is one of the insulin sensitising agents commonly used in the treatment of PCOS, 37 though it is still an unlicensed indication in PCOS. The mechanism of action of metformin is through inhibition of hepatic glucose production, increased glucose uptake and increased insulin sensitivity in the peripheral tissues.…”