Title : Metformin, pioglitazone, liraglutide and exenatide differentially affect metabolic and hormonal profiles in polycystic ovary syndrome: Cross-sectional study
Background and aims: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting up to 13% of women of reproductive age. Although the underlying pathogenesis of PCOS has not been fully understood, there is increasing evidence that supports insulin resistance (IR) and obesity are critically involved in the development and progression of the disease. Currently, the treatment for PCOS must always be individualized as universal treatment is not available. The purpose of this study was to help more clinicians provide more accurate drug selection for PCOS patients.
Materials and methods: This study was an observational cross-sectional study, with additional follow-up studies before and after treatment with four anti-diabetic drugs. 79 patients were treated with Metformin, 42 patients were treated with Pioglitazone, 31 patients were treated with Liraglutide and 30 patients were treated with Exenatide for 12 weeks. Metabolic and hormonal parameters in patients treated with different treatments for 12 weeks. Bioinformatics analysis was performed to explore the association of PCOS with metabolic-related genes and signaling pathways. Finally, we verified the inference of biological information in the crowd experiment.
Results: The BMI, Fins, HbA1c(%), and HOMA-IR decreased significantly, whereas M-value increased significantly in all treatment groups. The WHR decreased significantly in Pioglitazone and Exenatide group and blood pressure only decreased significantly in the Liraglutide group. All treatment groups have different extend of decrease in FBG, 2h-FBG, TG, TC, and LDL-C, but is most significant in Pioglitazone, Liraglutide, and Exenatide group. The HDL-C increased significantly and FFA decreased significantly only in the Pioglitazone treatment group. The AUC glucose is improved in all groups but the Metformin group, whereas the AUC insulin is improved in all groups but the Liraglutide group. There is a different extent of decrease in VAI, but is most significantly in Liraglutide and Exenatide group, whereas the BAI is significantly decreased in Metformin, Liraglutide, and Exenatide group but remains unchanged in Pioglitazon group. The TEST and FAI decreased significantly. The SHBG and LH decreased and progesterone increased significantly only in the Metformin group. We selected 5 obese control, 7 obese PCOS, 6 Normal-Weight control and 5 Normal-Weight PCOS from GSE10946. In GSE6798, we selected 13 morbid obese control and 16 morbid obese PCOS to analyse by “Connectivity Map”, we have still found 3 significant anti-diabetic compounds from the database-Gliclazide, Pioglitazone, and metformin. More importantly, Gliclazide yield a positive connectivity score , whereas Pioglitazone and metformin yield a negative connectivity score. The results indicate that Pioglitazone is suitable to treat lean PCOS subjects, whereas metformin is better in obese PCOS subjects, and Gliclazide is not suitable to use to treat PCOS in obese subjects. As there is no morbid obese subjects recruited in the study, we divided all patients into two groups: BMI < 24kg/m2 and BMI≥ 27kg/m2, according to the bioinformatic analysis. Pioglitazone treatment has a greater effect on ?WHR, ?2h-BG, ?2h-Ins, ?HbA1c(%), ?FFA, ?AUCglucose, ?AUC insulin and ?LH in the Lean group compared with Metformin treatment and metformin treatment has a greater effect on ?BMI, ?FBG, ?2h-FBG, ?FIns, ?2h-Ins, ?HOMA-IR, ?AUC glucose, ?AUC insulin, ?VAI, ?BAI, ?progesterone, and ?FAI are better improved compare with those values in metformin treatment in lean subjects which is consisted with Connective Map analysis.
Conclusions: As supported by clinical and bioinformatic evidence, pioglitazone seems to be better in treating lean PCOS patients, metformin provides higher value in correct hormonal parameters, and Gliclazide is not suitable to use to treat PCOS in Lean and Obese PCOS subjects. and our results also suggested that GLP-1RA would be better in treating obese subjects.
Audience Take Away:
- The treatment for PCOS must always be individualized as universal treatment is not available.The purpose of this study was to help more clinicians provide more accurate drug selection for PCOS patients.
- It suggests a novel idea which may help clinicians conduct studies on drug selection.