GLP-1s and PCOS Weight Management

What are GLP-1s?

GLP-1 agonists, or glucagon-like peptide-1 receptor agonists, more commonly known as “GLP-1s,” are a class of medications that help people with type 2 diabetes better regulate their glucose (blood sugar) levels. In recent years, several brands of GLP-1s have been approved to treat obesity (defined as abnormal or excessive fat accumulation with a BMI over 30). They work by mimicking a natural hormone in your body called glucagon-like peptide-1, which is released in the gut after you eat.

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Though GLP-1 medications are relatively new to the market, having only been FDA approved in the last 15-20 years, research around GLP-1s started as far back as the 1960s when researchers discovered the science behind a type of hormone called incretin. They found that incretins could stimulate insulin release, thereby helping control blood sugar.

List of GLP-1 Medications

The first GLP-1 medication was approved by the FDA in 2005. Since then, several others have received approval. The following are available on the U.S. market:

• Ozempic® (Semaglutide): A once-weekly injection, FDA-approved for the treatment of type 2 diabetes and kidney disease.
• Wegovy® (Semaglutide): A once-weekly injection FDA-approved for the treatment of obesity and the risk of cardiovascular events associated with obesity.
• Trulicity® (Dulaglutide): A once-weekly injection FDA-approved for the treatment of type 2 diabetes
• Victoza® (Liraglutide): A once-daily injection FDA-approved for the treatment of type 2 diabetes and the risk of cardiovascular events in people with type 2 diabetes. 
• Rybelsus® (Semaglutide): A once-daily oral GLP-1 FDA-approved for the treatment of type 2 diabetes
• Mounjaro® (Tirzepatide): A once weekly dual agonist (GLP-1/GIP receptor agonist) injection FDA-approved for the treatment of type 2 diabetes. Tirzepatides differ slightly from other GLP-1 medications, but work similarly. 
• Zepbound® (Tirzepatide): A once-weekly dual agonist (GLP-1/GIP receptor agonist) injection FDA-approved for the treatment of obesity and Obstructive Sleep Apnea.

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Manufacturers have discontinued several GLP-1 medications, including Byetta® (Exenatide) and Adlyxin® (Lixisenatide).

How Does a GLP-1 Work for Weight Loss?

GLP-1 medications mimic a hormone made in your small intestine called GLP-1. The hormone:

• Stabilizes blood sugar and reduces appetite by controlling insulin and glucose levels, reducing cravings and energy dips.
• Slows stomach emptying, meaning you feel fuller for a more extended period of time because food stays in your stomach longer.
• Targets brain receptors in some GLP-1s. Select medications may affect areas in the brain that regulate food intake and satiety.

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Essentially, the GLP-1 agonist attaches to a receptor in your brain, allowing it to function like the naturally occurring GLP-1. 

Common GLP-1 Side Effects

GLP-1 medications are generally safe as long as they are used under the management of a healthcare professional and within their FDA-approved label indications (i.e., what they are legally approved for). However, there are still side effects:

• Nausea and vomiting
• Constipation
• Diarrhea
• Rapid fat loss may cause hanging skin on the face and body (e.g., “Ozempic face”)
• Abdominal pain
• Fatigue 
• Dehydration

PCOS and Weight Management

Polycystic Ovary Syndrome (PCOS) is a hormonal disorder that affects many reproductive-aged women. Unexplained weight gain and difficulties losing and managing weight are some of the most common PCOS symptoms. There is evidence that GLP-1s are effective as a PCOS weight loss medication. 

How PCOS Affects Weight

Women with PCOS often struggle with weight management due to a hormonal imbalance. Specifically, women with PCOS tend to have higher levels of male hormones (androgens), as well as a condition called insulin resistance. Insulin resistance is when cells do not respond appropriately to insulin, a hormone made in the pancreas. These factors contribute to increased fat storage, particularly in the abdominal area. 

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Women with PCOS are often prescribed metformin to improve insulin sensitivity. This in turn, leads to a reduction in serum androgen levels and restoration of the menstrual cycle, which can trigger ovulation. However, metformin doesn’t always necessarily help with weight loss. While it can lead to some appetite suppression, it may not be enough for weight loss.

GLP-1s and PCOS

That’s where GLP-1s can step in as a potential PCOS treatment. We know that there is an interconnected relationship between PCOS and obesity, though it can be frustrating to understand. Obesity exacerbates PCOS, and many women with PCOS find it challenging to lose weight. Research shows that weight loss can improve insulin sensitivity and infertility, two common PCOS symptoms. 

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Given the effectiveness of GLP-1 medications as a weight loss treatment, some healthcare providers are looking into how these medications can ‘treat’ PCOS symptoms. In a recent metadata review, study authors found:

• GLP-1s have helped women with PCOS lose weight, reduce waist size, regulate their periods, and even boost fertility.
• Adding metformin amplifies these benefits, especially in women who have previously only tried Metformin.
• However, due to their off-label usage (which means a healthcare provider prescribes the medication for something other than its FDA-approved usage), the medicines are expensive and are often not covered by insurance. 
• There are also concerns about the effects of long-term use due to the lack of data we have around using these medications for weight management for extended periods of time.

Who May Benefit From GLPS-1s for PCOS Treatment

While research on the use of GLP-1s for PCOS is still emerging, several experts are already launching large-scale studies and exploring them as a viable option. In 2023, the American Society for Reproductive Medicine (ASRM) updated its guidance on treating PCOS to include a note about the potential of GLP-1s for weight management and improved fertility. If you have PCOS, you may benefit from GLP-1s if:

• You have struggled with weight management and have tried other methods, including medications like metformin.
• You also have insulin resistance, pre-diabetes, or diabetes
• You want to optimize your health and weight before trying to conceive (NOTE: there is limited safety data around GLP-1s and pregnancy. Currently, it is recommended to stop taking the medication two months before trying to conceive).

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It’s important to note that all GLP-1 medications work alongside diet and exercise. Consider working with a nutritionist, registered dietitian or a healthcare provider who can help you find a sustainable diet that works for you. Additionally, you should consult with your healthcare provider before taking any medication, and GLP-1s should only be taken under the supervision of a licensed professional.

How to get a GLP-1 for PCOS

Currently, there are no GLP-1 medications available on the market for the treatment or management of PCOS, which means any usage would be considered “off-label.” Health insurance usually does not cover off-label medications so they can be prohibitively expensive. A good place to start is speaking with your healthcare provider to review your options, and reaching out to your insurance company, who can explain what may or may not be covered under your plan. 

Which GLP-1 is Best for PCOS?

There isn’t a “best” GLP-1 for PCOS; everyone’s body is different, and some people see results on one drug, while others may see results on another. Research shows that Semaglutide and Liraglutide are both effective options, especially when combined with metformin. A recent trial comparing Tirzepitide to Semaglutide showed better weight loss results and improvement of diabetes. Your healthcare provider can best counsel you on what could be the most effective option for you, depending on your personal medical history and other factors.

Conclusion

GLP-1 medications aren’t a one-size-fits-all solution for PCOS, but they may offer benefits for women who have struggled to manage their weight. For some, combining GLP-1s with nutrition planning, regular exercise, and medications like metformin can improve weight, hormonal balance, and even fertility. However, questions remain about long-term safety, accessibility and cost, and the risks associated with pregnancy. As interest grows in using these drugs for PCOS, especially among women of reproductive age, more research is needed to fully understand their long-term impact and determine who can benefit most.

Key Takeaways

• GLP-1s are a class of medications originally developed to help people with type 2 diabetes manage blood sugar. More recently, several have been approved for obesity treatment.
• They mimic a natural hormone that helps regulate appetite, slow digestion, and stabilize blood sugar levels.
• PCOS is linked to hormonal imbalances and insulin resistance, which make weight management especially difficult for many women.
• Studies show GLP-1s may help women with PCOS lose weight, improve insulin sensitivity, regulate periods, and even boost fertility. These effects are enhanced when combined with metformin, a routine first-line medication for PCOS.
• GLP-1 medications are generally considered safe, but side effects can include nausea, vomiting, constipation, and rapid fat loss. Researchers are still studying long-term risks like thyroid issues or pancreatitis. Additionally, they are not recommended for women trying to actively conceive.
  
  

If you’re interested in a GLP-1 for PCOS, consult your healthcare provider and insurance company to understand your options and coverage. More long-term research is needed to better understand how GLP-1s impact PCOS and fertility, especially among reproductive-aged women.

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