6 best tirzepatide alternatives for weight loss in 2026

Tirzepatide (Zepbound) gets a lot of attention for good reason, but it's not the only option for weight loss. Here are six tirzepatide alternatives approved by the US Food and Drug Administration (FDA), from weekly injections to daily pills, along with the clinical evidence for each.

The best tirzepatide alternatives for weight loss are other FDA-approved medications, including semaglutide (Wegovy), orforglipron (Foundayo), liraglutide (Saxenda), phentermine/topiramate (Qsymia), and naltrexone/bupropion (Contrave).

None of these options produces quite the same degree of weight loss as tirzepatide on average. But each has strong clinical evidence behind it and may suit different health profiles, preferences, or insurance situations.

Part of what makes tirzepatide so effective is how it works. Ittargets two hormonal receptors at once — GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) — both of which play a role in appetite and blood sugar control.

People taking the highest dose of tirzepatide lost an average ofaround 20.9% of their body weight. The alternatives below generally work on only one of those receptors. This may partly explain why their average results are somewhat lower, but lower averages don't mean they won't work for you.

Several of these medications are also FDA-approved for type 2 diabetes under different brand names; this article focuses on their weight-loss uses and dosing.

Here's a closer look at each option.

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Semaglutide is the most comparable alternative to tirzepatide, acting on the same GLP-1 pathway and available as a once-weekly injection (Wegovy). It’s also available as oral once-daily tablet (Wegovy pill).

For people who need a weight-focused GLP-1 medication, Wegovy is often the first alternative a healthcare provider will suggest.

In clinical trials of the Wegovy pen, people taking:

• 2.4 mg of semaglutide lost an average of 14.9% of their body weight over 68 weeks

• 7.2 mg of semaglutide lost an average of 18.7% of their body weight over 72 weeks

Meanwhile, in clinical trials of the Wegovy pill, people taking 25 mg lost an average of 13.6% of their body weight over 64 weeks. 

A head-to-head comparison of semaglutide and tirzepatide found that tirzepatide (10 mg or 15 mg) produced an average weight loss of roughly 20.2% vs. 13.7% for semaglutide (either 1.7 mg or 2.4 mg, depending on what was tolerated).

Semaglutide also has FDA approval forreducing the risk of major cardiovascular events in adults with heart disease and obesity or overweight.

Wegovy side effects are similar to those of tirzepatide. Nausea, constipation, and diarrhea are among the most commonly reported, particularly early on in treatment and when increasing dosage.

One thing to know: Like tirzepatide, Wegovy also carries a boxed warning for thyroid C-cell tumors, based on rodent studies. It's unknown whether this applies to people, but as a precaution, semaglutide and tirzepatide shouldn’t be used by anyone with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).

Approved by the FDA in April 2026, orforglipron (Foundayo) is one of the newer oral GLP-1s approved for weight loss. Like the Wegovy pill, this treatment is taken once daily. Unlike the Wegovy pill, however, orforglipron doesn't require fasting or food and water timing restrictions. 

In trials, people on the highest dose of the drug lost an average of 11.2% of their body weight over about 72 weeks, producing weight loss in the range of other GLP-1 therapies, and among the higher results seen with an oral option.

Foundayo side effects are similar to those of other GLP-1 medications, with nausea, vomiting, constipation, and diarrhea among the most commonly reported. Like other GLP-1 drugs, it also carries a boxed warning for thyroid C-cell tumors.

Liraglutide (Saxenda) is an FDA-approved daily injectable medication that targets the same GLP-1 receptors as semaglutide, though its results are more modest. A generic version is also FDA-approved for weight management.

Liraglutide was one of the first GLP-1 medications approved specifically for chronic weight management, giving it one of the longest track records of any weight-loss drug.

In clinical trials, people taking 3 mg of liraglutide lost an average of about 8% (8.4 kg) of their body weight over 56 weeks, compared to 2.8 kg in the placebo group. That's lower than semaglutide or tirzepatide, but still a clinically meaningful result for many people.

The daily injection schedule isn't for everyone, though, and you may find a once-weekly format easier to stick with.

Saxenda side effects are similar to those of other GLP-1 medications and are mostly gastrointestinal. The same thyroid tumor precaution applies as with other GLP-1s: Liraglutide isn't suitable for anyone with a personal or family history of MTC or MEN 2.

Phentermine/topiramate (Qsymia) is an FDA-approved oral combination medication that suppresses appetite through two distinct mechanisms, making it one of the more effective non-injectable, non-GLP-1 options. It's taken once daily and is available in multiple doses.

In trials, people on the highest dose (15 mg/92 mg) lost an average of10.9% of their body weight over 56 weeks. 

It isn't suitable for people who are pregnant, as topiramate can cause birth defects. Other side effects include dry mouth, constipation, tingling in the hands or feet, and difficulty sleeping.

Because phentermine is a stimulant, it also isn't appropriate for people with certain heart conditions, uncontrolled high blood pressure, or hyperthyroidism.

Naltrexone/bupropion (Contrave) is an FDA-approved oral medication that primarily works in the brain, targeting both the appetite-regulation center (the hypothalamus) and the reward system — the part that can drive cravings and emotional eating.

In clinical trials, people taking naltrexone/bupropion lost an average of 6.4% of their body weight over 56 weeks, compared to 1.2% in the placebo group.

That's lower than the injectable options, but still enough to produce significant changes for many people. And for those who'd rather not inject, a twice-daily pill may be preferable.

Contrave carries a boxed warning for increased risk of suicidal thoughts, particularly in younger people, as bupropion is an antidepressant.

It also isn't appropriate for people with uncontrolled high blood pressure, a history of seizures, or those who have recently stopped using alcohol or sedatives, and shouldn't be used alongside long-term opioids or in anyone going through opioid withdrawal. Contrave is also contraindicated in pregnancy.

Orlistat is an FDA-approved medication that works in the digestive tract, blocking about a third of the fat you eat from being absorbed.

It's available by prescription (Xenical) and over the counter at a lower dose (Alli).

On average, orlistat produces 2.9% greater weight loss than placebo over one year. That's considerably lower than GLP-1 medications or phentermine/topiramate, but it can still be a reasonable option for people who may not be able to take other weight loss medications. 

The side effects are primarily gastrointestinal and directly tied to how much fat you eat: oily stools, urgent bowel movements, and fatty discharge. Sticking to a low-fat diet reduces these effects and helps with weight loss, too. 

Because orlistat reduces absorption of fat-soluble vitamins (A, D, E, K), consider taking a daily multivitamin at bedtime. This medication shouldn’t be used in pregnancy, either. There have been rare reports of kidney and liver injury. 

The options above vary significantly in how they work, how much weight loss they produce on average, and how often you take them.

*Figures show mean weight loss from each medication's main clinical trial and are not direct head-to-head comparisons; trial designs and lengths differ. Liraglutide's trial reported an average 8.4 kg loss (about 8% of the 106.2 kg average starting weight). Orlistat's figure reflects weight loss above and beyond placebo, rather than total average loss like the other rows, since that's how it's typically reported in trials.

Cost varies widely among these options and often comes down to insurance coverage.

While brand-name GLP-1 medications like semaglutide and tirzepatide can be more expensive (and harder to get covered) than older oral, non-GLP-1 options, there are ways to get them for lower out-of-pocket prices. 

On Ro, for example, you can get tirzepatide, semaglutide, and even orforglipron at the following cash-pay prices** (if prescribed):

• Tirzepatide (Zepbound KwikPen): $299-$449, depending on dose 

• Semaglutide (Wegovy pen and pill): $149–$399, depending on dose and form 

• Orforglipron (Foundayo): $149–$299, depending on dose 

A healthcare provider can help you weigh how well an option works against what's realistic for your budget and coverage.

**Terms and restrictions may apply for certain doses and drugs; prices may reflect limited-time offers and are subject to change.

There’s no natural or over-the-counter supplement that works the same way as tirzepatide.

Tirzepatidesimultaneously activates GLP-1 and GIP receptors to suppress appetite, slow stomach emptying, and improve insulin sensitivity — something no currently available supplement or herbal product has been shown to do.

Some supplements are marketed for weight loss and management (fiber, berberine, green tea extract, and others). But none appear to produce weight loss results close to those of prescription medications and have safety profiles that aren’t as established as those of prescription medications.

Several FDA-approved tirzepatide alternatives have solid evidence behind them, even if none work in exactly the same way. Here are the key points:

• Semaglutide (Wegovy) is the closest injectable alternative to tirzepatide, with a once-weekly dosing schedule and strong clinical backing, while orforglipron (Foundayo) is an oral GLP-1 with good weight loss results as well. 

• Liraglutide (Saxenda) works through a similar GLP-1 pathway as semaglutide and tirzepatide, but involves taking a daily injection and produces lower average weight loss.

• Phentermine/topiramate (Qsymia) and naltrexone/bupropion (Contrave) are non-GLP-1 oral options with lower but still clinically significant results for people who are unable to take GLP-1s or who'd rather not use injectable medications.

• Orlistat (Xenical, Alli) offers a different approach to weight loss by reducing how much fat your body absorbs. It’s available at a higher dose by prescription and at a lower one over the counter. It can be a good option for people who can’t take other weight loss medications. 

• Over-the-counter and natural supplements don’t come close to replicating tirzepatide's mechanism and have safety profiles that are less established than those of prescription medications. 

Any decision about starting or changing a weight loss medication should involve your healthcare provider. Ro connects you with licensed providers who can help you find the right option for your health goals.