Semaglutide Alternatives That Support Weight Loss

By now, semaglutide is part of the weight-loss conversation almost everywhere you look. This GLP-1 medication—best known by the brand names Ozempic, Wegovy, and Rybelsus—has helped many people lose weight and improve metabolic health, including blood sugar control and cardiovascular risk. For some, semaglutide during menopause has been genuinely life-changing especially when hormonal changes make it even harder to lose weight.

If you’re wondering whether there are semaglutide alternatives worth considering, from prescription options to supplements to lifestyle-based approaches, you’re not alone. Below, we’ll walk through the substitutes that exist today and what the research says about how they may support weight management, so you can make an informed choice that aligns with your body and your goals.

Why Look for Semaglutide Alternatives?

Semaglutide started its life as a treatment for type 2 diabetes, but as it's turned out, it has a whole resumé of other benefits that are independent of lowering blood sugar. Weight loss is simply the star player. 

The drug works by mimicking your body’s natural GLP-1 hormone. “It can slow digestion, tamp down appetite, boost feelings of fullness, and keep blood sugar under control—all of which promote weight loss,” says Kathleen Jordan, MD, Chief Medical Officer at Midi Health.

Even if you've always maintained a healthy BMI, midlife has a way of changing the game. Those hormonal shifts can invite extra pounds to settle in, particularly around your midsection. In fact, women gain an average of 1.5 pounds per year in midlife. (Yes, "menopot" is an unfortunate term, but it's also...not wrong.)

But semaglutide, like any medication, isn’t going to be the right fit for everyone. Cost, access, side effects, and personal preference all matter. Even when a medication is effective, it has to work for your life to be sustainable.

If you're interested in exploring more natural or lifestyle-based approaches that don't carry some of the side effects of semaglutide, like nausea, GI issues, and fatigue, here's what to consider.

Prescription Alternatives to Semaglutide

Semaglutide isn't the only GLP-1 on the market. Other options include:

• Tirzepatide (Mounjaro/Zepbound): This is the overachiever of the group—it’s a dual GIP and GLP-1 receptor agonist. No need to get caught up in all of those letters, although for the record, “GIP” stands for glucose-dependent insulinotropic polypeptide and “GLP-1” stands for glucagon-like peptide-1. The main thing to know is that tirzepatide works on two different hunger and satiety hormones in the body, as well as insulin levels. These meds are often less expensive than semaglutide, and a 2025 trial published in the New England Journal of Medicine that compared both medications found that tirzepatide was more effective for weight loss—helping participants drop up to 25% of their body weight over the course of the 72-week study. 
• Liraglutide (Saxenda/Victoza): This daily injectable works in a similar way to semaglutide. One recent study showed that both medications were equally effective at lowering body weight, although semaglutide had a bigger impact on hemoglobin A1c (HbA1c) levels, which is a measure of your blood sugar levels—meaning that it may be a better option for those living with diabetes or prediabetes. 
• Exenatide (Byetta/Bydureon): Exenatide is an earlier-generation GLP-1 that is currently less expensive than semaglutide, but it needs to be administered more frequently and doesn't appear to have the same results in terms of weight loss and blood sugar control. 
• Dulaglutide (Trulicity): This is a once-weekly medication, like semaglutide. It’s generally considered less effective at reducing weight and HbA1c. Dulaglutide also has a lower dosing range and doesn’t stay in the body for as long.
• Orforglipron: This is a soon-to-be-released, non-peptide GLP-1 pill that is showing promising results as an alternative to oral semaglutide (like Rybelsus or the new Wegovy pill). In late-stage trials, people taking orforglipron lost an average of about 12% of their body weight over roughly 72 weeks, and head-to-head studies suggest it may outperform standard oral semaglutide tablets (Rybelsus) in both weight loss and blood sugar control. Orforglipron is not yet FDA-approved.
• Other Rx medications: There are a variety of non-GLP-1 pharmaceuticals, such as Qysmia, Contrave, Orlistat and metformin, that have all been shown to help support weight loss among the right patients.  

Natural and Lifestyle-Based Alternatives

• Work with a nutritionist: A registered dietitian can develop a plan that works for your needs—whether it’s weight loss, blood sugar management, or any other health goals you have. Eating habits may not be enough for some people to make the numbers on the scale go down significantly, but it certainly can help, and adopting better food choices is always a good thing. Long-term management of weight loss is vital to keeping weight off. Plus, a nutritionist can guide you on other strategies, like how to eat more mindfully and avoid food triggers.
• Move regularly: Cardio exercise always gets the glory for its heart-pumping ability, but don’t sleep on strength training—especially during perimenopause and menopause. Starting around age 35, women start to lose muscle mass each year, and that rate speeds up over time, unless you do things like lifting weights or practicing yoga to maintain or build on what you have. While it’s true that cardio initially may burn more calories, which can support weight loss, muscle is much more metabolically active than fat. So the more you have, the more calories you’ll burn 24/7, whether you’re exercising or not.
• Consider berberine: This supplement has been dubbed “nature’s Ozempic.” Rather than mimicking the hormone GLP-1, berberine activates an enzyme in the body, called AMPK, that controls metabolism. Derived from the berry of the berberis shrub, berberine has been shown in several studies to help lower blood sugar levels and improve cholesterol levels—two health markers exacerbated in menopause. And a review of studies found that people taking berberine for at least 8 weeks lost a significant amount of weight—notably around their wasitline—and also saw improvements in cholesterol and blood sugar levels. "We pretty consistently see improved blood sugar levels and lipid panels in patients on berberine, while the weight loss response is mixed,” says Dr. Jordan. Always check with a healthcare professional before starting a new supplement, especially to ensure that it doesn’t interact with anything you’re already taking.
• Support your gut health: There’s evidence that taking prebiotics and probiotics may play a supportive role in immune function, hormone production, and mental well-being—and ultimately help with weight loss. However, some studies show only small declines, while others have found more promising ones, so more research is needed. Think of probiotics as one more tool—whether you want to give these supplements a go in addition to natural remedies like exercise and a healthy diet or a prescription like a GLP-1 (or all of them).

Are These Alternatives as Effective as Semaglutide?

None of these strategies promises to be a magic weight loss wand. Not even semaglutide is a “magic pill.” Lifestyle changes can take time and patience to stick and make a difference—but there’s no downside to making tweaks like eating a healthier diet and getting regular exercise.

And while alternative medications to semaglutide may kick-start your journey, all of them (including drugs like Ozempic) may need to be taken long-term to keep the pounds off. 

That’s why it’s important to talk with a clinician who specializes in both menopause and weight loss to find the right solution for you.

How to Choose the Right Alternative

The most important first step is to talk with a specialist, like a Midi clinician and develop a personalized plan together. Often it’s not one single thing that will get you to your goal, but a combo that fits with your health needs and what’s going to work for your lifestyle, preferences, and budget.

“Alternatives to Ozempic can be compounded and customized to give you the right dose of GLP-1s that are affordable and accessible,” says Dr. Jordan. That’s no small thing. And, she adds, they may be even more effective when added to other therapies, like HRT for weight loss, and lifestyle changes. Again, the bottom line is to consult a pro who can talk you through all of the options, so you can get the results you need. 

Key Takeaways

• There are multiple semaglutide alternatives, including other GLP-1 medications, non-GLP-1 prescriptions, supplements, and lifestyle-based approaches, that can help drive weight loss and other metabolic benefits.
• Tirzepatide and other prescription options may offer comparable—or even greater—weight loss for some people under medical guidance.
• Natural strategies like strength training, nutrition support, gut health, and supplements such as berberine can play a meaningful supporting role in any health journey.
• The most sustainable results usually come from a personalized plan that combines the right therapies for your body, life stage, and goals.

Frequently Asked Questions (FAQs)

What is the substitute for semaglutide?

It really depends on your goals. If you want the all-natural route, then lifestyle changes like a healthier diet, learning to eat more mindfully, or getting regular exercise may help. If you’re looking for a less costly alternative to a medication like semaglutide, you can explore other GLP-1 agonist options. Non GLP-1 meds like Qysmia, Contrave, orlistat or metformin are also options to discuss with your provider. 

Does anything work as well as semaglutide?

Some studies show that tirzepatide leads to even greater weight loss than semaglutide. Compounded prescriptions, under the right care, could get you where you want to go. But it’s important to get a treatment plan from a healthcare professional who is well-versed in both menopause and weight loss. 

How can I mimic Ozempic naturally?

The closest natural supplement you can try is berberine. It shows promise for weight loss, although more research needs to be done, and the results don’t appear to be as good as Ozempic.

Is there a pill equivalent to semaglutide?

Yes, there is a new, non-injectable version of oral semaglutide by Wegovy that came on the market in January 2026. Results, published in September 2025 in The New England Journal of Medicine, show that high-dose oral semaglutide tablets (25 mg) led to an average weight loss of about 14–17% over a little more than a year, along with additional benefits like lower blood pressure and reduced inflammation. These results begin to approach what we see with injections.