Weight Loss Medications: Which is Most Effective?

Success stories of weight loss medications, as well as their risks and side effects, seem to be everywhere these days—from local news to your social media feed.

Around 1 in 8 US adults have used a weight loss medication like semaglutide (brand names Ozempic®, Wegovy®), marking a more than 700% increase over the past four years.

But which of these weight loss medications is most effective? How do you know which one is for you? The answer to that question depends on a number of factors, from your baseline body weight to other health conditions you’re currently treating.

Ultimately, your doctor can help you decide on the best weight loss medication for you, but it’s helpful to head into your appointment with some background knowledge in hand. That’s where this article comes in.

Below, you’ll find a comprehensive guide to weight loss medications, including how they work, the results you can expect, and the risks you need to be aware of.

How Do Weight Loss Medications Work?

While Ozempic® and Wegovy® dominate most of the headlines, they are actually just two options when it comes to weight loss medication. Today’s weight loss medications generally fall into one of two categories: injectable vs. oral medications. Let’s take a look.

How Do Injectable GLP-1 Agonists for Weight Loss Work?

Injectable weight loss medications like semaglutide (brand name Wegovy®) and liraglutide (brand name Saxenda®) are known as glucagon-like peptide-1 receptor agonists, or GLP-1s for short. These medications work by mimicking a hormone your body naturally makes, called GLP-1, and acting on its receptors throughout your body.

Natural GLP-1 plays a role in regulating your appetite and blood sugar levels by slowing down digestion, encouraging the release of insulin (which lowers blood sugar), and limiting the release of glucagon (which raises blood sugar).

Naturally, the effects of GLP-1 only last for a matter of minutes, but when you take a GLP-1 medication, these effects last much longer—for around a week, in the case of Wegovy®, and around half a day, in the case of Saxenda®. That’s why Wegovy® is injected weekly, and Saxenda® is injected daily, to keep a steady amount of their active ingredient in your bloodstream.

As a result, people taking GLP-1s experience steadier blood sugar levels and lower appetites. They tend to feel full sooner and longer, too, since the medication slows down digestion, leaving food in their stomach for a longer period of time before it exits into the small intestine.

There’s also evidence that GLP-1s act on areas of the brain involved in food cravings and appetite, leading people taking them to experience fewer cravings and “food noise.”

Combined, these effects produce weight loss, and in people with type 2 diabetes, better blood sugar control. (Note: Ozempic® is actually FDA-approved to treat type 2 diabetes, not weight loss, but it may be prescribed off-label for weight loss).

In addition to GLP-1 agonists, there are also dual GIP/GLP-1 agonists like tirzepatide (brand names Mounjaro®, Zepbound®), which target an additional hormone receptor called glucose-dependent insulinotropic polypeptide, or GIP for short.

By targeting two receptors instead of just one, research suggests that these medications may be even more effective at weight loss. (Note: Of the two tirzepatide medications, only Zepbound® is FDA-approved for weight loss. Mounjaro® is FDA-approved for type 2 diabetes but may be prescribed off-label for weight loss.)

How Do Oral Weight Loss Medications Work?

Oral medications produce weight loss through different mechanisms than injectable GLP-1s. Orlistat (brand names Xenical®, Alli®) works by reducing the amount of fat your body absorbs by the food you eat—to the tune of 30%, in fact. It’s taken three times daily.

Other oral weight loss medications, such as phentermine/topiramate (brand name Qsymia®) and bupropion/naltrexone (brand name Contrave®) produce weight loss by suppressing your appetite. Both medications target your central nervous system, decreasing appetite and cravings through their effects on your hypothalamus. They’re taken one to two times daily, depending on the drug.

Whether you go with an oral or injectable option, all weight loss medications are intended to be used with other lifestyle changes like diet and exercise.

How Effective Are Weight Loss Medications? What the Research Says

Here’s a quick look at how much weight people lost in one year, according to research:

Weight Loss Medication	Type of Medication	1-Year Weight Loss Results*	Cost of Monthly Rx, Without Insurance**	Side Effects***
Wegovy® (semaglutide)	Weekly injectable GLP-1 agonist	12.4%	$1,590–$1,781	Nausea, diarrhea, vomiting, constipation
Saxenda® (liraglutide)	Daily injectable GLP-1 agonist	5.4%	$1,590–$1,732	Nausea, vomiting, abdominal pain
Zepbound® (tirzepatide)	Weekly injectable GIP/GLP-1 agonist	17.8%	$1,264–$1,313	Nausea, vomiting, diarrhea, constipation
Xenical ® (orlistat)	Thrice-daily oral lipase inhibitor	3.8%	$682–$888	Oily stool or spotting, increased defecation, sudden need to use restroom
Qsymia® (phentermine/ topiramate)	Daily oral appetite suppressant	8.6%	$244–$281	Tingling or numbness, dizziness, dry mouth, constipation
Contrave® (bupropion/naltrexone)	Twice-daily  oral appetite suppressant	4.8%	$750–$831	Nausea, vomiting, constipation, headache

*Weight loss is placebo-subtracted. These numbers reflect how much more weight people taking the medications lost compared to those taking a placebo, who generally lost 1–3% of their body weight, depending on the clinical trial.

**These prices reflect the average 12-month out-of-pocket prices for each medication at major pharmacies, according to SingleCare at the time of writing.

***This is not a complete list of the side effects for each drug, and only represents some of the most common.

Additional Impact

Research shows that these weight loss medications also lead to other beneficial impacts on metabolic health. For example, people taking Wegovy® saw improvements in their blood pressure, blood sugar levels, and cholesterol. In a study of Zepbound®, people experienced significant reductions in their blood pressure and lipid levels, which are linked to cardiovascular risk.

Potential Risks and Side Effects

While these drugs lead to impressive weight loss results, it’s worth noting that they have some downsides—including side effects, contraindications, drug interactions, high out-of-pocket costs, and the risk of weight regain when you stop taking them.

Side Effects

With most weight loss medications, the most common side effects are gastrointestinal in nature, such as nausea, vomiting, and diarrhea. Usually, these are worst at the beginning and when increasing your dose, and gradually subside as your body gets used to the medication. In some cases, they can be so intolerable that people stop taking the medication—up to 10% of people, in the case of GLP-1s.

While rare, other serious side effects can occur, including hypoglycemia, pancreatitis, kidney or gallbladder problems, or a risk of dependence (in the case of Contrave® and Qsymia®, which both contain controlled substances).

Contraindications 

Not everyone is a good fit for every weight loss medication. For example, people with a history of certain thyroid cancers should not take GLP-1s, while people with hypertension should not take Contrave® or Qsymia®. Overall, people who are pregnant should not take weight loss drugs. Always share your full medical history with your provider prior to starting any weight loss medication.

Drug Interactions

Because GLP-1s slow down gastric emptying, they can affect the absorption of other oral medications you take, including birth control pills. If you take insulin, your dose may need to be adjusted to avoid experiencing low blood sugar on GLP-1s. Oral appetite suppressants like Contrave® or Qsymia® have a longer list of drug interactions, including MAO inhibitors.

Out-of-Pocket Costs

Weight loss medications can be expensive, especially if you don’t have insurance. The out-of-pocket costs for a monthly refill range from about $250 to nearly $1,800, depending on the drug and the pharmacy. You can lower the cost by using pharmacy coupons and enrolling in any manufacturer savings programs, if you’re eligible.

Risk of Weight Regain

Many of these drugs, including GLP-1s like Wegovy® or Zepbound®, are intended to be taken on a long-term basis for weight loss and weight management. Once you stop taking them, the weight can come back, studies show. In one study, people stopped taking Wegovy® after 68 weeks; a year later, they had regained about two-thirds of the weight back.

Who Are They Best Suited For?

So, who’s a good fit for weight loss medications? Generally, these medications are FDA-approved for people who fall into one of two categories:

• People with obesity (defined as having a BMI of 30 or higher)
• People who are overweight (defined as having a BMI of 27 or higher) and a weight-related health condition such as high blood pressure, obstructive sleep apnea, or type 2 diabetes

If either of those describes you, and you’re interested in weight loss medication, talk to your healthcare provider. They’ll review your full medical history, current medications, and weight loss goals to determine the best and safest treatment plan for you.

Alternatives to Medications

There are other ways to lose weight besides taking weight loss medication, from lifestyle changes to surgery.

• Diet: When it comes to lifestyle changes, the biggest factor that leads to weight loss is achieving an energy deficit—in other words, consuming fewer calories than you burn. Reducing your daily caloric intake can help, as can increasing the amount of fiber and protein you eat. Both of these macronutrients increase feelings of fullness, enabling you to feel full longer. If you’re looking for a specific diet to follow, low-carb, low-fat, high-protein, Mediterranean, and vegetarian diets have all been shown to support weight loss.
• Exercise: Exercise has less of an impact on weight loss than diet, but it plays an important role in helping you keep the weight off. When losing weight, it’s especially important to take up regular resistance training (e.g. workouts that use weights, bands, or your own body weight to create resistance). These types of workouts help you build and maintain muscle, while regular cardio boosts fat burning.
• Surgery: Bariatric surgery can be a safe, effective, and lasting option for people with severe obesity, although it’s common to require a revision surgery later on. Based on a 20-year followup of over 8,300 people, the average weight loss was 22% compared to their starting weight.

Key Takeaways and Final Recommendations

Weight loss medications can be an effective option for people who want to slim down and live a healthier lifestyle. But, the best results come when they’re paired with lasting lifestyle changes like diet and exercise. Choosing the best weight loss medication for you can depend on your personal health history, weight loss goals, and budget. Here’s what to remember:

• Their effectiveness varies. Injectable medications like Wegovy® and Zepbound® tend to deliver the most weight loss, with Zepbound® currently leading the pack in clinical trials.
• Review the side effects and costs before making a final decision. Weight loss drugs can cause nausea and other GI issues, and the price of a monthly refill can range from a few hundred dollars to over $1,800 a month without insurance or discounts.
• They're not for everyone. Your eligibility depends on your BMI, health conditions, and current medications. Some people should avoid certain drugs altogether.
• Making sustainable lifestyle habits is key to success. Most people regain at least some of the weight after stopping the medication, especially if they don’t keep up with new lifestyle habits like a healthy diet and regular exercise.
• There are other options besides medication. If medication isn’t a good fit, you can still make meaningful progress with lifestyle changes, and for some, bariatric surgery may be an option.