Chapter 3: Medical Treatments for Obesity/Weight Loss

Weight loss medications have become a big help in managing chronic weight issues, especially if you meet certain criteria based on your BMI (that’s body mass index) and if you have other health problems related to your weight. Doctors typically consider these medications for adults with a BMI of 30 or higher, or for those with a BMI of 27 or higher who also have conditions like high blood pressure, type 2 diabetes or problems with their cholesterol levels. 

This is why it’s really important to understand what medical treatments are available for obesity and weight loss. We’ll cover FDA-approved pills and shots, how they work, and their possible side effects. We’ll also talk about diabetes medications that are used off-label for weight loss and take a peek at future weight loss drugs under clinical trials.

FDA-Approved Weight Loss Medications For Chronic Weight Management

The U.S. Food and Drug Administration (FDA) has approved several medications, available as both pills and injectables, for the long-term management of chronic weight issues in adults and, in some cases, adolescents. These work through various mechanisms like appetite suppression and mimicking natural hormones. 

Additionally, some medications approved for other conditions, notably diabetes drugs like certain GLP-1 receptor agonists, are increasingly being used “off-label” for their significant weight loss effects, alongside other appetite suppressant medicines.

FDA-Approved Oral Weight Loss Medications

There are several pills that have gotten the green light from the FDA for long-term weight management. These medications work in different ways to help you lose weight and prove to be most effective when combined with lifestyle modifications.

1. Orlistat (Xenical, Alli)

Orlistat first got FDA approval back in 1999, making it one of the early players in the weight loss medication game. You can also get a lower-strength version (60 mg) over-the-counter called Alli.

Orlistat works by blocking fat-digesting enzymes in your gut. It’s pretty good at its job – it can reduce the amount of dietary fat your body absorbs by about 30%. 

Studies suggest it works better at blocking fat from solid foods than from liquids. What makes orlistat different from many other weight loss medications is that it works in your digestive system rather than affecting your brain’s appetite control.

In rare cases, orlistat has been linked to serious liver injury and it might increase your risk of kidney stones.

You shouldn’t take it if you’re pregnant or breastfeeding, or if you have certain digestive disorders.

As for how well it works, orlistat typically leads to modest weight loss compared to placebo. Therefore, it might not work as well as newer medications like liraglutide and semaglutide.

2. Phentermine (Adipex-P, Lomaira)

Phentermine is one of the oldest and most widely used weight loss medications, having been approved by the FDA in 1959. Initially used as a short-term medication to jump-start weight loss, newer guidelines have added it to long-term therapy. 

Phentermine helps with weight loss by increasing the release of norepinephrine in your brain, which helps suppress your appetite. It also boosts your energy expenditure as it acts as an adrenergic agonist.

Interactions may occur during or within 14 days following the use of monoamine oxidase (MAO) inhibitors, sympathomimetics, alcohol, adrenergic neuron-blocking drugs, and possibly some anesthetic agents.

Phentermine is contraindicated in individuals with hyperthyroidism, glaucoma, or heart disease, or who have had a stroke. It is also contraindicated during pregnancy. Some patients may lose about 5% of their body weight by taking phentermine.

3. Phentermine-Topiramate (Qsymia)

Phentermine-topiramate is a combo medication that got FDA approval in 2012. It combines two drugs that work together: phentermine and topiramate.

Topiramate, which is also used to treat epilepsy and prevent migraines, helps with weight loss by making food less appealing and potentially making you feel fuller. This combo approach targets different pathways involved in controlling appetite and feeling satisfied.

You shouldn’t take it if you’re pregnant, or if you have glaucoma, hyperthyroidism or if you’ve taken certain antidepressants (MAOIs) in the past 14 days.

It’s been linked to an increased risk of cleft lip and palate in babies if taken during early pregnancy. Because of the birth defect risk, there’s a special program in place to educate about prescribing information and monitor during treatment.

4. Naltrexone-Bupropion (Contrave)

Naltrexone-bupropion is another combo pill approved by the FDA in 2014 for chronic weight management. It’s not currently available in the VA formulary.

This medication combines naltrexone, which is mainly used to treat alcohol and opioid dependence, and bupropion, an antidepressant that affects certain brain chemicals. This combo is thought to target both the system in your brain that regulates appetite and the pathways involved in food cravings.

There’s a risk of suicidal thoughts and behaviors associated with bupropion, so doctors need to monitor patients carefully.

You shouldn’t take it if you have uncontrolled high blood pressure, seizure disorders, eating disorders like anorexia or bulimia, if you’re using opioids, or if you’re taking certain antidepressants. This highlights why it’s important for your doctor to know your full medical history before prescribing this medication.

While it might not be as powerful for weight loss as some other options, it may be particularly helpful for controlling food cravings.

FDA-Approved Injectable Weight Loss Medication

Besides pills, there are several injectable medications approved by the FDA for long-term weight management. These medications, mostly GLP-1 receptor agonists (a fancy term for drugs that mimic a natural hormone in your body), have shown they can be really effective for weight loss.

1. Liraglutide (Saxenda)

Liraglutide, sold under the brand name Saxenda, was approved by the FDA in 2014 for chronic weight management. It’s also approved for teenagers aged 12 to 17 years.

Liraglutide is a GLP-1 receptor agonist, which means it mimics the effects of a hormone your body naturally produces. This hormone helps regulate appetite, makes you feel fuller and slows down how quickly food empties from your stomach.

It’s also approved for kids aged 12 to 17 with obesity (BMI at or above the 95th percentile for their age and sex) and who weigh more than 60 kg, when used along with a reduced-calorie diet and increased physical activity. 

You shouldn’t take it if you or your family have a history of certain types of thyroid cancer or a condition called MEN 2.

However, studies suggest it might not work as well for weight loss as semaglutide and tirzepatide.

2. Semaglutide (Wegovy)

Semaglutide, sold as Wegovy, got FDA approval for chronic weight management in 2021. It’s also approved for teenagers aged 12 years and older. Plus, Wegovy is approved to reduce the risk of major heart problems, like heart attack or stroke, in adults with established heart disease who are also obese or overweight. 

Semaglutide also comes in a pill form (Rybelsus) which is approved for type 2 diabetes but is being studied for weight loss. As an injectable, semaglutide is a GLP-1 receptor agonist, similar to liraglutide, but it lasts longer in your body, so you only need to take it once a week.

Like liraglutide, you shouldn’t take it if you or your family have a history of certain types of thyroid cancer or MEN 2.

It’s been shown to work better than liraglutide for weight loss. However, some studies suggest that tirzepatide might lead to even more weight loss compared to semaglutide.

3. Tirzepatide (Zepbound)

Tirzepatide, sold as Zepbound, is the newest FDA-approved injectable medication for chronic weight management, getting approval in 2023. It’s also approved for treating moderate-to-severe sleep apnea in adults with obesity. 

Tirzepatide stands out because it’s the first medication that works on two different receptors – both the GLP-1 and GIP receptors. This dual action helps reduce appetite and food intake, slow down how quickly your stomach empties, increase insulin release, and lower glucagon (another hormone) secretion.

Clinical trials have shown that tirzepatide leads to significant weight loss compared to placebo and semaglutide (Wegovy). This makes tirzepatide one of the most effective medications currently available for weight loss.

4. Setmelanotide (Imcivree)

Setmelanotide is a newer medication, approved by the FDA in 2020. It works by activating a receptor in your brain called the melanocortin-4 receptor (MC4R). When this receptor is activated, it helps regulate appetite and energy expenditure, which leads to decreased hunger and increased calorie burning.

The criteria for prescribing setmelanotide are very specific. It’s only for people age 6 and older who have obesity due to certain rare genetic conditions, including POMC deficiency, PCSK1 deficiency, or LEPR deficiency, which must be confirmed through genetic testing. This very specific patient group reflects how targeted this drug is.

In people with these rare genetic conditions, setmelanotide has shown significant weight loss. This shows how effective it can be for this very specific genetic subset of people with obesity.

List of Off-Label Drugs for Weight Loss

Off-label use means using a medication for a condition or in a way that isn’t approved by the FDA.

Several medications approved for treating type 2 diabetes have been found to cause weight loss as a side effect and are sometimes used off-label for this purpose.

1. GLP-1 Receptor Agonists (Ozempic, Rybelsus)

GLP-1 receptor agonists, such as semaglutide (Ozempic, Rybelsus), liraglutide (Victoza), dulaglutide (Trulicity), and exenatide (Byetta/Bydureon), are mainly approved for lowering blood sugar in people with type 2 diabetes. 

These medications slow down how quickly your stomach empties and reduce your appetite. A significant benefit seen with these drugs is weight loss. 

In fact, Ozempic contains the same active ingredient (semaglutide) as Wegovy, which is approved for weight loss, but at lower doses.

Rybelsus, which is an oral form of semaglutide, is approved for type 2 diabetes but has shown weight loss comparable to Wegovy in higher doses studied in clinical trials. The manufacturer has indicated plans to seek FDA approval for its use in weight management.

However, the off-label use of these diabetes medications for weight loss has raised concerns about potential shortages for patients with diabetes who rely on them for blood sugar control. Additionally, the risks associated with these medications when used for weight loss are generally similar to those seen with the weight loss formulations.

2. Dual Gip And Glp-1 Receptor Agonist (Mounjaro)

Mounjaro, which contains the same active ingredient (tirzepatide) as the weight loss drug Zepbound, is approved for type 2 diabetes and has been observed to cause significant weight loss, leading to its off-label use for obesity.

Clinical trials showed an average weight loss of 34 pounds over 72 weeks with Mounjaro. The side effects of Mounjaro when used off-label for weight loss are expected to be similar to those of Zepbound, including nausea, diarrhea, and vomiting.

3. SGLT2 Inhibitors

SGLT2 inhibitors, including canagliflozin (Invokana), empagliflozin (Jardiance), and dapagliflozin (Farxiga), are another class of diabetes medications that have shown some weight loss benefits. 

These oral medications work by increasing the amount of glucose you pee out, leading to a modest loss of calories. While they mainly target blood sugar control, they’ve been linked to a modest weight loss of about 3 to 5 pounds over 6 months.

The potential risks of SGLT2 inhibitors include an increased risk of urinary tract and genital infections, dehydration, and a condition called ketoacidosis. The weight loss seen with SGLT2 inhibitors is generally less than with GLP-1 agonists, and they have different potential side effects.

4. Metformin

Metformin is a widely used oral medication for type 2 diabetes that works by reducing how much glucose your liver produces, increasing your body’s sensitivity to insulin, and may also affect your appetite and gut bacteria. Along with its blood sugar-lowering effects, metformin has been shown to cause modest weight loss, with some studies reporting an average loss of over 12 pounds in 6 months.

The main risks with metformin are digestive side effects, such as diarrhea and nausea. Metformin is a well-established and generally safe medication, and its modest weight loss benefit can be an extra advantage for overweight or obese people with type 2 diabetes.