Semaglutide Alternatives That Support Weight Loss During Menopause

GLP-1 (glucagon-like peptide-1) receptor agonists like semaglutide, sold under brand names such as Ozempic and Wegovy, help many people achieve significant weight loss. That can be especially helpful during menopause, when up to 70% of women gain weight, even if their diet and exercise habits haven’t changed.

But the truth is, GLP-1 receptor agonists aren’t designed for everyone.  

Between potential side effects, high costs, strict insurance coverage requirements, and personal preferences, it’s completely reasonable to explore your options, whether that means different forms of GLP-1 medications or other approaches to weight care during menopause.

Why Weight Loss Feels More Challenging During Perimenopause and Menopause

Among the many things that change in your body during perimenopause, one is your ability to maintain the same weight.

During this part of life, your estrogen levels dramatically ping-pong up and down before eventually bottoming out in menopause. You may be wondering, how exactly does this affect your waistline? Well, estrogen wears many hats in your body. It helps regulate where your body stores fat, your appetite, and how efficiently your body uses energy.

This is why you may notice fat beginning to crop up more around your belly (something colloquially known as menopause or “meno” belly), even if your healthy diet and exercise routine are consistent. At the same time, muscle mass begins to decline, which can quietly slow your metabolism. (Less muscle means your body burns fewer calories at rest, and it becomes less efficient at managing blood sugar.)This combination (more fat, less muscle) can make it feel impossible to shed pounds.

“We see women in perimenopause struggle with this very issue.  It is important to remember that even though you are changing, you are not failing.  It can feel like you are gaining weight even when you are doing everything “right”,  but you can take control of your weight and long-term health.” - Dr. Kristen Leezer

Why Semaglutide Isn’t For Everyone

So here’s the thing: semaglutide works. Like, it really works for some people. But the keyword here is “some.” 

For others, the juice isn’t worth the squeeze. GLP-1s can come with a host of side effects, particularly gastrointestinal ones such as nausea, constipation, or acid reflux. 

Some women may have medical contraindications, such as a history of pancreatitis or certain thyroid cancers. 

Then there’s the very real issue of cost and access. Insurance coverage often comes with strict requirements, like a BMI of 30 or higher, a diagnosis of type 2 diabetes, or a BMI of at least 27 with additional risk factors. Without coverage, these medications can cost over $1,000 per month.

Personal preference is also a real consideration. GLP-1 medications aren’t something you take temporarily. You’re often on them for life, so you have to ask yourself, is that something you can commit to or maintain long-term?

All of these concerns are valid reasons to consider semaglutide alternatives. 

Lifestyle Strategies: The First Step in Menopausal Weight Management

Even when it feels like your hormones are controlling the show, lifestyle strategies are still the foundation of weight management.

Just not in the way you may have been taught.

During midlife, the goal shifts from simply eating less to eating strategically. Prioritizing protein helps preserve muscle mass, while fiber-rich foods support blood sugar control and keep you feeling full longer. The Mediterranean diet (rich in vegetables, whole grains, healthy fats, and lean proteins) is associated with better metabolic health in postmenopausal women.

Exercise matters, too! Strength training, in particular, helps you maintain your muscle and, in part, support your metabolism. In one study of women going through the menopause transition, the proportion of lean mass declined by about 0.6% per year while fat mass increased.

That’s exactly the kind of shift regular physical activity can help counter.

In one randomized trial, women who exercised for about 45 minutes, five days a week saw meaningful reductions in body weight, overall fat, and abdominal fat over time. And there’s a bit of a compounding effect here: the more consistently women moved, the more fat loss they saw.

The other missing piece? Sleep. Poor sleep can disrupt hunger hormones and increase appetite, while chronic stress can promote fat storage.

Non-GLP-1 Medication Options for Menopausal Weight Loss

Other medications can support weight loss, and depending on your health history, they may actually make more sense. 

Some work by reducing appetite. Others change how your body absorbs fat. 

Some target the brain’s reward pathways around food (because, despite what you may have been told, willpower alone isn’t enough to fend off cravings sometimes!).

One option you’ll hear about is a combination of bupropion and naltrexone, which can help curb appetite and dial down cravings. There’s also orlistat, which blocks some fat absorption in the gut. Though fair warning, the side effects can affect your bowel movements (we’ll just leave it at that). 

There are off-label options, like low-dose naltrexone, that sometimes come into play, especially when you’re dealing with inflammation or metabolic dysfunction.

Then there are medications like metformin, which you’ve probably heard of. It’s typically used for blood sugar regulation, especially in those with insulin resistance or prediabetes, but some women also notice a bit of weight loss, too.

In general, these alternative options may lead to more modest weight loss compared to GLP-1s, but not everyone needs to lose a bunch of weight during this life stage.

Compounded Liraglutide: A More Accessible GLP-1 Option

Semaglutide tends to get all the attention, but it’s not the only GLP-1 option out there (not even close!).

Liraglutide is another GLP-1 medication that can be custom-made through regulated compounding pharmacies. Keep in mind that compounded versions of liraglutide aren’t regulated by the United States Food & Drug Administration (FDA), so where you source it from matters. (Compounding pharmacies are often overseen by state pharmacy boards and follow guidelines set by the U.S. Pharmacopeia.)

“At Alloy, we partner with a pharmacy to provide compounded liraglutide. Regarding safety, the medication is prepared by a licensed compounding pharmacy that follows strict quality and sterility standards. These pharmacies are regulated and must follow state and federal compounding guidelines. Each batch is prepared under controlled conditions and the dosing concentration is standardized so we can prescribe accurately.” - Dr. Kristen Leezer

“Both semaglutide and liraglutide work by binding the GLP-1 receptor, but the main difference between the two is the half life”.  The long half life of semaglutide allows for weekly dosing while liraglutide requires daily dosing.  Semaglutide is a bit more potent as well.  The combination of these properties mean that we often see more weight loss with semaglutide.”  - Dr. Kristen Leezer

The liraglutide option requires daily injections versus weekly, which, for some women, is an understandable dealbreaker.

For others, though, cost or access is the main barrier to GLP-1 use, and this can help resolve it. (But you should always consult with your healthcare provider before choosing to go on a GLP-1 medication).

Compounded Tirzepatide: What to Know

Tirzepatide , sold under the brand name Zepbound, is another touted medication used for weight loss and metabolic health. It works a bit differently than traditional GLP-1 medications. Specifically, it targets two pathways involved in appetite and blood sugar regulation, which may lead to greater weight loss for some people. Much like semaglutide, tirzepatide is typically administered as a weekly injection.

You may also come across compounded versions of tirzepatide, just like liraglutide and semaglutide. Like other compounded medications, these are not FDA-approved and are made by specialized compounding pharmacies. (AKA, quality, dosing consistency, and sourcing can vary depending on where the medication is prepared). 

For some women, compounded tirzepatide may offer a more accessible option when cost or insurance coverage is a barrier. But as with any GLP-1–based therapy, it’s important to work with a clinician who can help determine whether it’s appropriate for you and monitor your response over time.

Can Menopausal Hormone Therapy Help With Weight Management?

Let’s get one thing straight: Menopausal hormone therapy (MHT) isn’t a weight loss treatment.

But it can make weight loss feel a lot more feasible.

As mentioned above, declining estrogen levels means your body is more prone to storing fat, especially around your abdomen. Your body also becomes less efficient at managing blood sugar as a result. MHT helps smooth some of that out. It can support fat distribution around your thighs and butt (which is healthier than the visceral fat that can accumulate around the organs in your tummy area), improve insulin sensitivity, and ease symptoms like poor sleep and hot flashes that can interfere with your routines.

When you pair MHT with other strategies, such as lifestyle changes and, yes, even GLP-1 use,  weight loss can be pretty powerful. In one recent study, postmenopausal women using hormone therapy alongside a GLP-1 medication, specifically tirzepatide, lost more weight (19.2% of their bodyweight versus 14%) and saw greater improvements in cardiometabolic markers than those who didn’t take MHT.

How to Choose the Right Weight Loss Approach for You

The bottom line is this: what works for one person likely won’t work for another, and that’s okay. You don’t need a GLP-1 to lose menopausal weight gain. You don’t need a GLP-1 to manage menopausal weight gain. Other strategies, including diet, exercise, and medications like metformin or a combination of bupropion and naltrexone, can help.

Where you’re at in your menopause transition, your unique medical history, and personal preferences (and health goals!) all matter. 

Reframing the question “what option is the most effective?” to “what options work best for me and my body?” can help inform the decision you and your doctor make.

Talk with a menopause-expert clinician about your options, what to expect, and how medications of any kind fit alongside other treatments like MHT. 

Remember, the right plan for you is the one you can comfortably (and confidently) stick to.

Frequently Asked Questions

Why is losing weight and preventing weight gain more difficult during perimenopause and menopause?

Weight management becomes more challenging because fluctuating and declining estrogen levels alter how your body handles energy, appetite, and fat storage. Instead of storing fat evenly, the body begins depositing it around the abdomen, a phenomenon often called "menopause belly." Simultaneously, a natural decline in muscle mass slows down your resting metabolism and makes the body less efficient at managing blood sugar. These hormonal and body composition shifts mean you can experience weight gain even if your healthy diet and exercise routines remain completely unchanged.

What are the main alternatives to semaglutide for menopausal weight management, and how do they work?

For those who cannot take or prefer not to use semaglutide, several options exist across lifestyle, non-GLP-1 medications, and other compounded therapies. Strategic lifestyle shifts focus on a Mediterranean diet rich in protein and fiber to preserve muscle, alongside consistent strength training to support metabolism. Non-GLP-1 prescription options include a bupropion-naltrexone combination to curb cravings, orlistat to block gut fat absorption, and metformin to improve blood sugar regulation. Additionally, compounded GLP-1 alternatives like daily liraglutide or weekly tirzepatide can provide more accessible pathways when cost or insurance coverage presents a barrier.

How does Menopausal Hormone Therapy (MHT) assist with weight management if it isn't a direct weight loss treatment?

While MHT is not prescribed as a primary weight loss medication, it makes shedding pounds more feasible by stabilizing declining estrogen levels. MHT helps favorably redistribute fat storage away from dangerous visceral abdominal fat and toward the thighs and buttocks, while also improving insulin sensitivity. Furthermore, by alleviating disruptive symptoms like hot flashes and poor sleep—which actively interfere with your daily routine and disrupt hunger hormones—MHT creates a healthier metabolic foundation. When paired with other interventions, it can even boost effectiveness; one study showed women combining MHT with tirzepatide lost significantly more body weight than those using the weight loss medication alone.