What side effects are associated with this type of intervention?

Metformin, an insulin sensitizer commonly used to treat PCOS, can cause gastrointestinal side effects such as nausea, diarrhea, and abdominal discomfort. It may also lead to vitamin B12 deficiency with long-term use. Clomiphene citrate, used for ovulation induction, can cause hot flashes, bloating, and mood swings. Oral contraceptives, often prescribed to manage menstrual irregularities and hyperandrogenism, can lead to weight gain, breast tenderness, and an increased risk of blood clots. Lifestyle modifications, including diet and exercise, are generally safe but require sustained effort and commitment.

What prior FDA approvals exist?

Metformin, an insulin sensitizer, is widely used for the treatment of PCOS, particularly for improving insulin resistance and menstrual cyclicity. While Metformin is not FDA-approved specifically for PCOS, it is commonly prescribed off-label for this condition. Other treatments for PCOS include GLP-1 receptor agonists like liraglutide and semaglutide, which are FDA-approved for obesity and type 2 diabetes and have shown benefits in weight reduction and glycemic control in PCOS patients. Additionally, statins are used to manage dyslipidemia in PCOS, although they do not significantly impact other metabolic or endocrine aspects of the syndrome.

What other types of research exist?

Promising novel alternatives to Metformin for PCOS treatment include: 1) Rimonabant, which has shown superior efficacy in reducing biochemical hyperandrogenemia and insulin resistance in obese PCOS patients. 2) GLP-1 receptor agonists (e.g., liraglutide, exenatide, semaglutide), which improve glycemic control, delay gastric emptying, and reduce food intake, potentially benefiting metabolic aspects of PCOS. 3) Letrozole, particularly for ovulation induction, has shown better outcomes compared to clomiphene citrate. These alternatives offer different mechanisms of action and may provide additional benefits over Metformin.

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Biguanide

Metformin for Polycystic Ovary Syndrome

Phase 4

Waitlist Available

Led By Aviva B Sopher, MD, MS, MS

Research Sponsored by Columbia University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

At least 2 years postmenarche

Be younger than 65 years old

Must not have

Any diseases affecting bone metabolism (collagen disorders, primary hyperparathyroidism, nephrolithiasis, untreated hyperthyroidism), indwelling hardware

Nonclassical congenital adrenal hyperplasia (CAH) - early morning 17-hydroxyprogesterone level less than 200 ng/dL

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial is testing metformin, a common diabetes medication, to see if it can reduce liver fat in young people with polycystic ovary syndrome (PCOS). The study focuses on adolescents and young adults who have high liver fat and are at risk for non-alcoholic fatty liver disease (NAFLD). Metformin works by helping the body use insulin more effectively, which may lower liver fat. Metformin is an antidiabetic drug widely used to improve insulin resistance and has shown potential benefits in treating non-alcoholic fatty liver disease (NAFLD).

Who is the study for?

This trial is for healthy girls and young women aged 13-25 with PCOS, diagnosed by NIH criteria. They should have signs of high male hormones or irregular periods but no other health issues affecting metabolism, no recent hormonal contraceptives or metformin use, and not be pregnant.

What is being tested?

The study tests if Metformin can reduce liver fat in young females with PCOS compared to a placebo. It's a double-blind trial where neither participants nor researchers know who gets Metformin or the placebo until the end of the study.

What are the potential side effects?

Metformin may cause digestive upset like nausea, diarrhea, stomach pain; it might also lead to vitamin B12 deficiency over time. Side effects vary from person to person.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I started my periods at least 2 years ago.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I do not have conditions like collagen disorders or untreated thyroid issues affecting my bones.

Select...

My early morning 17-hydroxyprogesterone level is below 200 ng/dL.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Difference in percentage liver fat between Metformin arm and Placebo arm in adolescents and young adults with PCOS and with elevated percentage liver fat (>/=4.8%)

Secondary study objectives

Fatty acid glycerol esters

Insulin Resistance

The association of percentage liver fat with M30, a hepatic apoptosis marker

+4 more

Side effects data

From 2015 Phase 4 trial • 156 Patients • NCT02002221

13%

Nasopharyngitis

10%

Hyperhidrosis

Hunger

Tremor

Asthenia

Hypoglycaemia

Femoral neck fracture

Squamous cell carcinoma of the tongue

100%

80%

60%

40%

20%

Study treatment Arm

Vildagliptin (LAF237)

Placebo

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: MetforminExperimental Treatment1 Intervention

Adolescents and young adults with PCOS and liver fat greater than or equal to 4.8% will be randomized to metformin or placebo. Metformin ER (extended release) will be administered as two pills of 500 mg each. For the first week subjects will take one pill orally on a daily basis and thereafter will take two pills orally on a daily basis. The intervention will last six months.

Group II: PlaceboPlacebo Group1 Intervention

Adolescents and young adults with PCOS and liver fat greater than or equal to 4.8% will be randomized to metformin or placebo. Subjects randomized to placebo will be instructed to take one pill daily by mouth for one week and then to take one pill daily by mouth for the remainder of six months.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Metformin

2006

Completed Phase 4

~2430

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Polycystic Ovary Syndrome (PCOS) include insulin sensitizers like Metformin, which work by improving the body's sensitivity to insulin. This is crucial for PCOS patients as insulin resistance is a common feature of the condition, leading to elevated insulin levels that can exacerbate hyperandrogenism (high levels of male hormones) and menstrual irregularities. By enhancing insulin sensitivity, Metformin helps to lower insulin and androgen levels, thereby improving ovulatory function and reducing symptoms such as hirsutism and acne. This mechanism is particularly important for managing the metabolic and reproductive abnormalities associated with PCOS.

Metformin and polycystic ovary syndrome.