Which Weight Loss Medications Work Best for PCOS?

Weight loss is one of the primary treatments for obese females with PCOS. Weight loss is associated with significant improvement in ovulation and fertility.

Among the weight loss medications, Orlistat has been used in clinical trials and found to be effective to some extent.

However, the novel GLP-1 analog, Semaglutide (Rybelsus and Ozempic) is considered a promising treatment for PCOS.

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PCOS (Polycystic Ovarian Syndrome) is a common gynecological condition that affects up to 7% of women in their reproductive ages.

It manifests as irregular menstrual cycles, excessive facial hair growth (hirsutism), clinical and biochemical features of high androgen levels in the body, and infertility.

It has been estimated that up to 40 – 80% of women with PCOS are either overweight or obese. Along with obesity, females with PCOS have insulin resistance and Beta-cell dysfunction [Ref].

In fact, PCOS, Obesity, and Diabetes are now considered a spectrum of the same disorder called Metabolic Syndrome. Other features of the metabolic syndrome are hypertension and hyperlipidemia (high cholesterol levels).

Obesity is considered the basic problem causing PCOS, Diabetes, Hyperlipidemia, and Hypertension in the majority of patients. Hence, targeting weight loss is one of the major goals when treating these conditions.

Furthermore, there are no approved medications for PCOS. Even the widely used diabetes drug metformin has not been approved for the treatment of PCOS.

Drugs that are currently being used to treat PCOS include:

• Metformin
• Spironolactone (Aldactone)
• Finasteride and Flutamide
• Drugs that stimulate ovulation such as clomiphene citrate and Letrozole
• Eflornithine
• Insulin-sensitizing agents include pioglitazone, Rosiglitazone, D-chiro-inositol, and statins.
• GLP-1 analogs especially, the novel GLP-1 analogs Semaglutide (Rybelsus and Ozempic)

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Medications that have been approved for Weight loss include:

• Orlistat (Xenical, Alli)
• Phentermine/ Topiramate (Qsymia)
• Naltrexone/ Bupropion (Contrave)
• Lorcaserin
• Liraglutide (Saxenda, Victoza)
• Semaglutide (Rybelsus, Ozempic, and Wegovy)

Which Weight Loss Medications Work Best for PCOS?

None of the above-mentioned weight loss medications have been approved for weight loss. However, almost all of these weight loss medications have been tried in clinical trials in obese patients with PCOS.

It is obvious that the pill that induces the most weight loss will work the best in obese patients with PCOS.

Even for obese females who struggle to conceive, a 10% weight loss increases the likelihood of pregnancy without the need for medications.

Weight loss Medications for PCOS:

• Orlistat (Xenical, Alli) for PCOS:

Orlistat (Xenical, Alli) is one of the weight-loss medicines that has been studied in the treatment of patients with PCOS.

It is one of the safest medicine approved for weight loss and is also available as an OTC medicine.

It was compared with metformin and placebo medicine in obese patients with PCOS in a study.

All patients had a BMI exceeding 23 kg/m² and were younger than 40 years of age.

Along with the study drugs, all patients also received a low-calorie diet and were enrolled in the fertility fitness program.

The results of the study are tabulated here [Ref]:

Table 1: Ovulation rates as seen via transvaginal ultrasound (P: 0.008):

Table 2: Percentage  of patients who conceived (P: 0.003):

Table 3: Percentage changes in the obesity parameters in each group:

• Phentermine/ Topiramate (Qsymia) for PCOS:

Phentermine/ Topiramate (Qsymia) is one of the most potent drugs used in the treatment of obesity.

It is a combination of two drugs: phentermine and topiramate. Phentermine is a stimulant drug that is used for weight loss because of its anorexiant effect.

The mechanism of action of Topiramate for weight loss is not yet known. However, it has an anorexiant effect as well.

Phentermine/ topiramate (Qsymia) has not been extensively studied in obese females with PCOS.

In one single-blinded randomized trial, phentermine/ topiramate (Qsymia) resulted in an equivalent reduction in the testosterone and free androgen index compared to once-weekly Exanetide and Dapagliflozin [Ref].

Phentermine/ topiramate (Qsymia) may be used for weight loss and hence used as an adjunct to other therapies in the treatment of PCOS.

Since weight reduction results in significant improvement in the symptoms of PCOS, phentermine/ topiramate can be tried in obese patients with PCOS for weight loss.

However, it may not be of great benefit in lean patients with PCOS.

• Naltrexone/ Bupropion (Contrave) for PCOS:

Naltrexone/ Bupropion (Contrave) is a combination of an atypical antidepressant drug and opioid antagonist.

The combination has been approved for the treatment of obesity and overweight individuals. In patients with PCOS, psychiatric disorders have been found in about half of the patients.

The most common psychiatric disorder found in patients with PCOS was depression. Up to 33% of the patients with PCOS had symptoms of depression [Ref].

Binge eating is another common disorder in these patients that also causes weight gain. Depression alters insulin sensitivity which is also one of the causes of diabetes and obesity.

Naltrexone/ Bupropion (Contrave) is an attractive alternative in the treatment of PCOS patients who are obese.

It helps to alleviate the neuropsychiatric features associated with PCOS including binge eating.

Furthermore, it helps patients to lose weight resulting in significant improvement in the symptoms of PCOS [Ref].

• Lorcaserin for PCOS:

Lorcaserin is another weight loss medicine. It was initially approved for weight loss by the FDA. However, lorcaserin was withdrawn from the market because of its association with certain malignancies.

It is not recommended for either weight loss or for the treatment of PCOS.

• Liraglutide (Saxenda, Victoza) for PCOS:

Liraglutide (Victoza, Saxenda) is an approved medicine for the treatment of diabetes and obesity. It belongs to the class of drugs called GLP analogs.

Liraglutide was studied in females with PCOS in a study [Ref]. It was found to cause a weight loss of about 5.2 kg from the baseline.

Compared to the placebo medicine, it significantly reduced serum testosterone levels, reduced ovarian volume, and improved ovarian function.

Liraglutide has been studied in obese patients with metabolic syndrome and PCOS. It induces weight loss through its direct effects on the gastrointestinal tract and via central mechanisms.

It inhibits hunger by acting on the hypothalamic centers of the brain.

In patients with PCOS, liraglutide was associated with significant weight loss and improvement in insulin sensitivity and secretion.

It increases the levels of AMH (anti-mullerian hormone) that are strongly associated with fertility. It also inhibits androgen synthesis and improves ovulation [Ref].

• Semaglutide (Rybelsus, Ozempic, and Wegovy) for PCOS:

Semaglutide is among the latest drugs primarily indicated for the treatment of diabetes and obesity.

Among all the weight loss drugs, Semaglutide use is associated with the greatest reduction in body weight.

In the STEPS trials, Semaglutide was found to cause a weight loss of up to 16% from baseline at week 56.

Semaglutide is available in three different strengths and formulations.

• Rybelsus is a once-daily oral Semaglutide indicated for the treatment of diabetes.
• Ozempic is a once-weekly Semaglutide that is used to treat patients with diabetes mellitus type 2.
• Wegovy is also administered once weekly, however, it is used in a dose of 2.4 mg compared to Ozempic which is administered in a dose of 0.5 to 1 mg once a week.

Wegovy is primarily indicated for the treatment of obesity.

Semaglutide is being studied in obese patients with metabolic syndrome and PCOS. The results are yet to be finalized.

However, patients with diabetes and PCOS who have been using Rybelsus or Ozempic have found the drug to significantly improve the symptoms of PCOS.

Semaglutide (Ozempic, Rybelsus, and Wegovy) can improve the symptoms of PCOS by enhancing insulin sensitivity, reducing abdominal and visceral fat, inhibiting androgen synthesis, and improving ovulation.

In Summary:

Among the six weight-loss drugs, we are only left with five drugs. Lorcaserin is out and has been withdrawn from the markets since its use has been associated with Cancers.

Among the five weight loss medicines,  phentermine has been associated with significant weight loss, however, data regarding its use in patients with PCOS is limited.

One study compared Orlistat, Liraglutide, and Bupropion in patients with PCOS. The authors concluded that Orlistat has some role in patients with PCOS, however, the role of bupropion and liraglutide is yet to be explored [Ref].

The last and novel agent Semaglutide is among the most promising drug. It is associated with significant weight loss and off-trials data strongly suggests its role in obese females with metabolic syndrome and PCOS.

Weight loss medications for PCOS in order of efficacy are Semaglutide (Ryebelsus & Ozempic), Orlistat (Xenical, Alli), Liraglutide (Saxenda, Victoza), Naltrexone/ bupropion (Contrave), and Phentermine/ Topiramate (Qsymia).

People who shared their experiences regarding menstrual cycles while using Ozempic have been posted in the article here: Ozempic and Menstrual Cycle: How Women Describe Their Experience