Metformin Effects on Metabolic, Vitamin B12, Iron, Erythropoietin, and Hematological Parameters in Women With PCOS

NCT07793838 | Completed Phase 4

• 1 other identifier: Metformin-Placebo-2026
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

This double-blind, placebo-controlled, parallel-group randomized controlled trial evaluated changes in metabolic, vitamin B12, iron-status, erythropoietic, and hematological parameters among women with polycystic ovary syndrome (PCOS) receiving metformin therapy. Women aged 18-40 years with a diagnosis of PCOS confirmed by a specialist in Obstetrics and Gynecology were randomly assigned in a 1:1 ratio to either a metformin intervention group or a matching placebo group. Participants in the metformin group received a total daily dose of 1500 mg metformin, administered in three divided doses with meals, while participants in the control group received a matching placebo. Both groups continued to receive routine clinical care. Clinical and laboratory assessments were performed at baseline, 3 months, and 6 months. The study evaluated metabolic measures, including fasting blood glucose, serum insulin, HOMA-IR, total cholesterol, triglycerides, LDL-C, HDL-C, and body mass index. Iron-status measures included serum iron, total iron-binding capacity, ferritin, and transferrin saturation. Serum vitamin B12 and erythropoietin were also assessed, together with hematological parameters including hemoglobin, hematocrit, red blood cell indices, white blood cell counts and differential counts, and platelet count. The study enrolled 400 participants, with 200 participants initially allocated to each treatment group. After loss to follow-up, 300 participants completed the required assessments and were included in the final longitudinal analysis, with 150 participants in each group. The study was designed to characterize longitudinal changes in metabolic, nutritional, iron-related, erythropoietic, and hematological parameters during six months of metformin therapy in women with PCOS.

Conditions

Polycystic Ovary Syndrome (PCOS) Women

Keywords

Metformin; Insulin Resistance; Polycystic Ovary Syndrome; HOMA-IR; Vitamin B12; Iron Status; Ferritin; Erythropoietin; Hematological Parameters

Outcome Measures

Primary Outcomes (27)

• Longitudinal change in serum iron

  Change in serum iron from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months

• Longitudinal change in total iron-binding capacity

  Change in total iron-binding capacity (TIBC) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months

• Longitudinal change in serum ferritin

  Change in serum ferritin from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months

• Longitudinal change in transferrin saturation

  Change in transferrin saturation (TSAT) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months

• Longitudinal change in serum vitamin B12

  Change in serum vitamin B12 level from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in erythropoietin

  Change in serum erythropoietin (EPO) level from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in hemoglobin

  Change in hemoglobin (Hb) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in hematocrit

  Change in hematocrit (Hct) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in red blood cell count

  Change in red blood cell (RBC) count from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in mean corpuscular volume

  Change in mean corpuscular volume (MCV) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in mean corpuscular hemoglobin

  Change in mean corpuscular hemoglobin (MCH) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in mean corpuscular hemoglobin concentration

  Change in mean corpuscular hemoglobin concentration (MCHC) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in red cell distribution width

  Change in red cell distribution width (RDW-CV) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in white blood cell count

  Change in white blood cell (WBC) count from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in lymphocyte count

  Change in lymphocyte count from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in neutrophil count

  Change in neutrophil count from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in eosinophil count

  Change in eosinophil count from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in basophil count

  Change in basophil count from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in monocyte count

  Change in monocyte count from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in platelet count

  Change in platelet (PLT) count from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in HOMA-IR

  Change in homeostasis model assessment of insulin resistance (HOMA-IR) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months

• Longitudinal change in fasting blood glucose

  Change in fasting blood glucose (FBG) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months

• Longitudinal change in total cholesterol

  Change in total cholesterol (TC) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months

• Longitudinal change in triglycerides

  Change in triglycerides (TG) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months

• Longitudinal change in low-density lipoprotein cholesterol

  Change in low-density lipoprotein cholesterol (LDL-C) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in high-density lipoprotein cholesterol

  Change in high-density lipoprotein cholesterol (HDL-C) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

• Longitudinal change in body mass index

  Change in body mass index (BMI) from baseline through 3 months and 6 months during the study intervention.

  Baseline, 3 months, and 6 months.

Study Arms (2)

Metformin Intervention Group

EXPERIMENTAL

Participants assigned to the metformin intervention group received metformin at a total daily dose of 1500 mg, administered in three divided doses with meals, for six months in addition to routine clinical care. Clinical and laboratory assessments were performed at baseline, 3 months, and 6 months.

Drug: Metformin

Matching Placebo Group

PLACEBO COMPARATOR

Participants assigned to the matching placebo group received a corresponding matching placebo according to the same administration schedule for six months in addition to routine clinical care. Clinical and laboratory assessments were performed at baseline, 3 months, and 6 months.

Drug: Matching Placebo

Interventions

Metformin DRUG

Metformin was administered at a total daily dose of 1500 mg in three divided doses with meals for six months.

Metformin Intervention Group

Matching Placebo DRUG

A matching placebo was administered according to the same schedule as the metformin intervention for six months.

Matching Placebo Group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 18-40 years.
• Diagnosis of polycystic ovary syndrome (PCOS) confirmed by a specialist in Obstetrics and Gynecology.
• Eligible participants who met the study requirements and provided written informed consent.

You may not qualify if:

• Chronic hemolytic anemia.
• Chronic kidney disease.
• Endocrine disorders other than PCOS.
• Hepatic disorders.
• Metabolic disorders.
• Cardiovascular disease.
• Other concurrent medical conditions that could influence glucose metabolism, iron status, vitamin B12, erythropoietin, or hematological parameters.
• Previous use of insulin-sensitizing agents, iron supplementation, hormonal therapy, vitamin B12 supplementation, or other medications known to substantially affect glucose metabolism, iron metabolism, erythropoietin levels, or hematological parameters during the predefined period before enrollment.

Sponsors & Collaborators

• Jerash Private University: lead

Study Sites (1)

obstetrics and gynecology clinics affiliated with the Ministry of Health in Jordan،

Amman, 009627, Jordan

Location

Related Publications (2)

• Escobar-Morreale HF. Iron metabolism and the polycystic ovary syndrome. Trends Endocrinol Metab. 2012 Oct;23(10):509-15. doi: 10.1016/j.tem.2012.04.003. Epub 2012 May 10.

  PMID: 22579050 RESULT

• Greibe E, Trolle B, Bor MV, Lauszus FF, Nexo E. Metformin lowers serum cobalamin without changing other markers of cobalamin status: a study on women with polycystic ovary syndrome. Nutrients. 2013 Jul 5;5(7):2475-82. doi: 10.3390/nu5072475.

  PMID: 23857221 RESULT

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Insulin Resistance

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants and investigators involved in participant assessment and outcome evaluation were blinded to treatment assignment. Metformin and matching placebo preparations were provided under otherwise identical study conditions to minimize the possibility of identifying treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor doctor

Model Details: Participants were randomly allocated in a 1:1 ratio to two parallel groups: a metformin intervention group and a matching placebo group. The assigned intervention was continued for six months, with assessments conducted at baseline, 3 months, and 6 months.

Study Record Dates

• First Submitted: August 22, 2026
• First Posted: August 31, 2026
• Study Start: August 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: August 1, 2026
• Last Updated: August 31, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

JO (1)