Xenical to Zepbound: How Anti-Obesity Drugs Have Evolved in 25 Years
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Key Takeaways
25 years ago, a drug called Xenical was approved by the FDA to help people lose weight.
Today, newly approved, headline-making drugs like GLP-1 and GLP-1/GIP agonists are more effective at reducing BMI than older weight loss drugs like Xenical, which worked in a different way.
Experts say the benefits usually outweigh the side effects of taking Wegovy and Zepbound, but these drugs are still expensive and not available to everyone who is trying to lose weight.
The Food and Drug Administration (FDA) approval of GLP-1 agonists Wegovy (semaglutide) and Zepbound (tirzepatide) were major moments in recent weight loss drug history, but the medications are not the first to make headlines.
In 1999, Xenical (orlistat), a lipase inhibitor, was approved for weight loss. With the 25th anniversary of the drug’s approval coming up in April, it’s the perfect time to explore how the new generation of weight loss medications compares to older ones and how the weight loss drug market continues to evolve.
Related: New Weight Loss Drug Could Upstage Wegovy and Ozempic
GLP-1 Agonists: New Players in the Long Game of Weight Loss
Obesity—medically defined as having a body mass index greater than 30—is considered a public health emergency, with over 42% of adults in the United States falling into the category and 9% (1 in 11 people) meeting the criteria for having severe obesity.
Even as obesity cases have risen, there hadn’t been a major advancement in weight loss medications since Xenical in the late 1990s until recently. It was only last year that a headline-making clinical trial discovery showed that GLP-1 agonists used to treat type 2 diabetes can also be effective at helping people lose weight.
“Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 dual-acting medications have completely changed the field in their effectiveness,” Colleen Tewksbury, PhD, RDN, a national spokesperson for the Academy of Nutrition and Dietetics, told Verywell. “Prior to these medications, most anti-obesity medications were modestly effective.”
So far, the FDA has only approved three of these drugs for weight loss: Saxenda, Wegovy, and Zepbound. Other GLP-1 agonists, such as Ozempic and Trulicity, are only FDA-approved to treat type 2 diabetes, not weight loss.
Saxenda
Saxenda (liraglutide), a once-daily injectable GLP-1 type 2 diabetes drug, was approved by the FDA for chronic weight management in 2014. It was the first GLP-1 to be approved for weight loss in people who don’t have diabetes.
In 2020, the FDA updated the approval so that the drug could also be used to treat obesity in children and teens.
The reason that GLP-1 medications are getting so much attention is, quite simply, that they are very effective compared to the drugs that came before them. And 25 years ago, that was Xenical.
“Xenical demonstrated a weight loss of about 5% total body weight,” Dan Azagury, MD, section chief of Minimally Invasive and Bariatric Surgery at Stanford University, told Verywell. “However, GLP-1s show three to four times the effectiveness as Xenical. Most importantly, of all the patients who would take Xenical, only a small minority would see that effect. The major change with GLP-1s is that non-responders are an exception rather than the rule, with a 90% response rate.”
Related: 7 FDA-Approved Drugs for Weight Management
Xenical vs. Wegovy and Zepbound
In addition to effectiveness and response rate, several other factors separate GLP-1s from Xenical, including how they work, how they are taken, their side effects, and how much the treatment costs.
How They Work
Xenical, Zepbound, and Wegovy can all help with weight loss but work in different ways.
Xenical is a lipase inhibitor that blocks the absorption of some of the fat a person consumes, which can support weight loss when it’s used along with other management strategies like diet and exercise.
OTC Orlistat
Xenical is the prescription form of orlistat, but you might be familiar with over-the-counter orlistat products like Alli. These lower-dose versions are found in most grocery stores and pharmacies and can also be purchased online.
Zepbound is a dual-acting GIP and GLP-1 receptor agonist that’s approved to treat type 2 diabetes and obesity. GLP-1 and GIP work together to make the stomach empty slower, which helps increase the feeling of satiety and reduce appetite, as well as helps manage blood sugar levels.
Wegovy is a GLP-1 receptor antagonist that’s approved to treat obesity. It works similarly to Zepbound by slowing gastric emptying, which makes you feel full faster and can reduce or even stop food cravings.
Related: Why People With Obesity Can’t Access Powerful Weight Loss Drugs
How Well They Work
The biggest difference between lipase inhibitors and GLP-1s is how effective they are.
Studies have shown that Xenical helped reduce participants’ body weights by 5% or more after one year of treatment. A smaller number of people achieved a 10% reduction in body weight.
While those rates are enough to be considered effective, compare them to the rates of people taking Wegovy, who lose an average of 15% of body weight, and Zepbound, who lose about 21%.
Wegovy and Zepbound also outrank Saxenda in terms of weight loss: people taking Saxenda for 68 weeks lost around 7.4% of their body weight, which is more on par with Xenical than newer GLP-1s.
So, while Xenical works, GLP-1s just seem to work better. It’s also important to note that diet and lifestyle changes (like exercising regularly) are recommended, along with taking the medications to get the most weight loss benefits.
Related: What's New in Obesity Treatment?
How They’re Taken
Another key difference between Xenical and newer weight loss drugs is administration.
Xenical is an oral capsule that’s taken three times a day, one dose with each meal.
Zepbound and Wegovy are not taken orally. These drugs are given with a subcutaneous injection pen that’s administered once a week (on the same day of the week). The dose can be taken with or without food.
The Wegovy injection pen comes in different doses (0.25 mg–2.4 mg). Usually, people start with the lowest dose and increase the dose every four weeks as tolerated until the maximum dose of 2.4 mg is reached.
The Zepbound injection pen comes in a single dose. People typically start with a dose of 2.5 mg for four weeks. The dose is incrementally increased each week as tolerated until a maximum dose of 15 mg is reached.
Related: Which Anti-Obesity Drugs Do Patients Stay On Longest?
Side Effects and Risks
All medications can have side effects and risks, and weight loss drugs are no different. It’s important for you to talk to your provider about these aspects of taking the medications so that you can make an informed choice about your treatment.
Side effects of Xenical include:
Flatulence
Increased bowel movements
Fatty/oily stool
Headache
Loss of appetite
Nausea and vomiting
Abdominal pain
Rectal discomfort
Zepbound and Wegovy have similar gastrointestinal side effects, including:
Diarrhea
Nausea
Vomiting
Constipation
Abdominal pain
Hair Loss
Headache
Fatigue
Dizziness
Related: The FDA Is Investigating Reports of These Serious Side Effects from Weight Loss Drugs
How Much They Cost
While weight loss drugs can be an effective way to treat obesity, they are not currently covered by health insurance. Many people who might benefit from prescription weight loss medications can’t access them due to the cost.
None of these weight loss drugs are cheap: Xenical costs around $700 out of pocket for 90 capsules, while Wegovy and Zepbound can cost upwards of $1,000 a month.
“Cost is prohibitive and insurance coverage is the main issue,” said Azagury. “Those are both big barriers to adoption, in particular for patients with lower socio-economic statuses who often would benefit the most. There are some side effects, but the benefits vastly [outweigh] the risks and side effects.”
Are Any Non-GLP-1 Drugs FDA-Approved for Weight Loss?
There are a few other FDA-approved prescription medications for weight loss that are not GLP-1s:
Contrave (bupropion-naltrexone): Antidepressant/opioid antagonist (used along with diet and exercise to treat obesity)
Qsymia (phentermine-topiramate): Indirect sympathomimetic/antiseizure (used along with diet and exercise to treat obesity)
Imcivree (setmelanotide): Melanocortin receptor agonist (specifically treats a type of severe genetic obesity)
The Future of Weight Loss Drugs
With the approval of GLP-1 and GLP-1/GIP medications for weight loss, we are entering a new era in obesity treatment. However, some experts are concerned that with so much focus on effective treatment, we will stop trying to figure out what causes obesity and work on prevention.
“Weight loss medication is a good strategy to reduce obesity, but it’s a multi-pronged approach. Prevention is key as a nation and is the ultimate goal,” said Azagury. “But that will take decades/generations. We need to treat patients who are fighting the condition right now, and the best tools available are surgery and GLP-1s.”
What This Means For You
Newer weight loss drugs have come a long way from the older options, but they’re still limited by cost and side effects. It’s best to talk with your provider about the best approach to obesity treatment for your needs, as there is no one-size-fits-all approach to health.
Read the original article on Verywell Health.
