GLP-1 Medications Affect Men and Women Differently — Here’s Why That Matters

GLP-1 medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounarjo, Zepbound) can do a lot — often, a whole lot — to help manage conditions like obesity and diabetes and improve overall metabolic health. But while many people do very well on these drugs, some have less success, for a variety of causes.

One of those reasons may be sex: Researchers are learning that men and women react differently to GLP-1s based on factors like hormones and body composition.

That doesn’t mean every woman or every man will respond the same way to a GLP-1, but a person’s sex may be a consideration when setting expectations, managing side effects, and planning treatment.

“We looked at lots of different factors that might be plausibly associated with efficacy of these products, and sex was the only one of the five or six that we looked at where we found significantly different effects,” says coauthor Caleb Alexander, MD, an internist, epidemiologist, and co-director of the Center for Drug Safety and Effectiveness at Johns Hopkins Medicine in Baltimore.

Those other factors included age, race, ethnicity, baseline body mass index (BMI), and baseline HbA1c (a test measuring average blood sugar levels over several months).

Researchers don’t know exactly why there’s a gap between women’s and responses to GLP-1s, but a few theories are emerging:

Body composition may matter. Women generally have a higher percentage of body fat and lower muscle mass than men, while men tend to have more lean mass and higher baseline metabolic rates. Those differences may affect how weight loss shows up on the scale, how quickly it happens, and what kind of weight is lost, says Matthew L. Holt, PharmD, assistant professor of pharmacology at PCOM South Georgia in Moultrie.

Estrogen may amplify GLP-1’s effect. Estrogen, the main female sex hormone, might interact with GLP-1s in a way that enhances the drug’s impact. “GLP-1 medications may interact synergistically with estrogens, which could potentially amplify the weight loss effect in women,” says Dr. Alexander. This could include brain pathways that help regulate food intake and reward.

Women may be more likely than men to have the gastrointestinal side effects most associated with GLP-1 medications, especially nausea, vomiting, and diarrhea.

A preprint study (meaning it has not yet been peer-reviewed for publication in a medical journal) found that women taking semaglutide (Wegovy) or tirzepatide (Zepbound) had a 2.5-fold higher rate of nausea and vomiting compared with men.

Because weight, insulin resistance, and sex hormones are closely connected, GLP-1s may influence reproductive health differently in women and men.

Here’s How Hormones May Interact With GLP-1s in Women

GLP-1s may help with PMOS (polyendocrine metabolic ovarian syndrome). This condition, formerly known as PCOS (polycystic ovary syndrome), is often tied to insulin resistance and higher levels of androgens (so-called male sex hormones like testosterone that female bodies typically produce at low levels).

In women, excess androgens can contribute to symptoms such as irregular periods, acne, unusual body-hair growth, ovulation problems, and fertility challenges. PMOS also tends to be associated with excess weight, although people at a healthy weight can also have the condition, says Marilyn Tan, MD, an endocrinologist at Stanford Medicine in California.

Because GLP-1 medications can improve blood sugar, appetite, insulin sensitivity, and weight, researchers are studying whether the drugs may also improve some of the metabolic and hormone patterns that drive PMOS.

GLP-1s may boost female fertility. “For women with obesity and diabetes, weight loss and improved diabetes control can sometimes help normalize previously irregular menstrual periods and increase fertility,” says Dr. Tan.

Some women previously struggling to conceive have found the medications have raised their odds of pregnancy, hence the term “Ozempic babies.”

Women who are trying to avoid pregnancy should know that oral birth control may be less reliable for women on GLP-1s. “When starting a GLP-1, and during subsequent dose increases, the absorption of oral birth control tablets is altered, and that can make birth control pills less effective,” says Dr. Holt.

GLP-1s may help with postmenopausal weight gain. Estrogen — or more precisely, the lack of it during menopause, when the ovaries dramatically reduce their output — may impact how GLP-1s work.

First the good news: GLP-1s can help offset the “very real and very common” issue of postmenopausal weight gain, says Tan.

Because of the limitations of this type of study, the research can’t prove that hormone therapy directly caused the additional weight loss — but it supports the idea that estrogen may influence how some women respond to GLP-1s.

For Men, GLP-1s May Help Increase Low Testostone Levels

For men, the reproductive effects appear to be mostly indirect.

Obesity can contribute to lower testosterone, and weight loss may help some men if low testosterone is related to excess weight, says Tan.

A narrative research review found early evidence that GLP-1 medications may improve some sperm measures or testosterone levels in men with obesity or metabolic hypogonadism (a condition that impacts hormone production).

Who Loses More Muscle on a GLP-1, Women or Men?

Major weight loss can include some loss of lean mass, including bone and muscle. While any kind of significant weight loss can have this result, it tends to be more common in people taking a GLP-1 compared with those dropping pounds from diet and lifestyle changes alone, says Tan.

Losing too much muscle mass may lead to sarcopenia, a condition marked by loss of muscle mass and strength that can make it harder to stay active, steady on your feet, and independent. This condition is more common in older adults, in part because levels of hormones that help protect muscle — including sex hormones, growth hormone, and related growth factors — tend to decline with age, says Michael Schwartz, MD, a researcher and professor of medicine, metabolism, endocrinology, and nutrition at UW Medicine in Seattle.

Whether men or women lose more lean mass on GLP-1 medications is still unclear, he says. “While you could say that men have more lean muscle mass, and so they’re more apt to lose it, you also have to consider that because women have less, they have less to spare,” says Dr. Schwartz.

That is why muscle preservation, including resistance training and a diet that provides adequate protein, should be part of the GLP-1 treatment plan for both men and women.

Resistance training can also help offset loss of bone mass, Holt notes, decreasing the risk of osteopenia (loss of bone density) and osteoporosis (bone disease) that is particularly common in postmenopausal women.

Men on GLP-1s May Lose More Belly Fat Than Women Do

In general, men tend to have more visceral fat (a particularly harmful type of fat surrounding the abdominal organs) compared with subcutaneous fat (under the skin), says Holt. “This may lead to higher reductions in waist size for men than women when taking a GLP-1,” he says.

But fat shifts during weight loss are dependent on the person and not necessarily linked to sex, says Tan.

Someone may be thin with little subcutaneous fat but can still have significant visceral fat, while someone with significant subcutaneous fat may not have as much visceral fat.

“This is part of the explanation how some people may be overweight or obese but ‘metabolically healthy,’ and someone else with a normal BMI [body mass index] may not be as ‘metabolically healthy,’” says Tan.

It’s good to have an awareness of sex-specific risks, but the impact of a GLP-1 is still mostly based on the individual and their specific health conditions.

That means that people on GLP-1s should have a plan tailored to their particular issues, whether that’s diabetes, PMOS, fertility concerns, significant menopausal symptoms, low muscle mass, high cardiovascular risk, some combination of the above, or something else entirely.

That said, some groups of women merit especially close monitoring. Those who could become pregnant should talk with their clinician about pregnancy testing, contraception, and the timing around stopping a GLP-1 medication before trying to conceive, since these drugs are not approved for use during pregnancy, Holt says.

Postmenopausal women who lose a significant amount of weight may also need to pay extra attention to bone health to guard against osteopenia or osteoporosis, he adds.

• Women may lose more weight than men on GLP-1 medications, but sex is only one part of how a person responds to these drugs.
• Women may be more likely to have nausea, vomiting, fertility changes, and birth control concerns, so pregnancy plans should be discussed early.
• Sex-related differences will likely take a backseat to other considerations tailored to the individual and their unique health challenges.