Weight Loss Pills: How They Work, Safety, and History

For many patients today, a decision about which weight loss medication to try may come down to several factors, including what other medications they take, which drugs are covered by insurance or are most affordable, and whether people prefer pills or injected medicines, Dr. Jay says.

“I advise people to speak to their physician to choose an initial medication and see how they respond,” Jay says. “It’s not uncommon to switch medications or have to add a second or third medication.”

Here’s what you need to know about the prescription weight loss drugs that are currently approved.

Tirzepatide (Zepbound)

This weekly injected medicine was approved by the FDA in 2023 to treat adults with obesity and overweight adults with at least one weight-related chronic health problem.

How it works: Tirzepatide mimics two hormones that regulate insulin secretion and digestion: glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). It is widely believed to be the most potent weight loss drug ever approved for sale: In the SURMOUNT-1 trial, participants using the highest dose lost an average of 22.5 percent of their body weight.

Common side effects: Nausea, diarrhea, vomiting, and constipation.

Interactions and risks: Rare but potentially dangerous reactions include severe gastrointestinal disease and acute injury to the pancreas, kidneys, or gallbladder.

Semaglutide (Wegovy)

Wegovy was approved by the FDA to treat adults with obesity as well as adults who are overweight and also have at least one weight-related chronic health problem. The weekly injected form of the medicine was approved in 2021, and the once-daily oral version was approved in 2025.

How it works: It’s another GLP-1 receptor agonist that mimics a hormone in the brain that regulates appetite.

Common side effects: Nausea, diarrhea, vomiting, constipation, stomach pain, headache, and fatigue.

Interactions and risks: It can’t be used in combination with liraglutide or other GLP-1 receptor agonists that are prescribed for type 2 diabetes. Like other drugs in this family of medicines, including tirzepatide and liraglutide, it carries an increased risk of pancreatitis and has been linked to thyroid tumors in animals.

Naltrexone-Bupropion (Contrave)

This oral drug was approved by the FDA in 2014.

How it works: It’s a combination of two drugs that are used to treat addiction and depression, and it suppresses appetite and makes people feel full sooner.

Common side effects: Constipation, dizziness, diarrhea, dry mouth, headache, increased blood pressure, elevated heart rate, insomnia, liver damage, nausea, and vomiting.

Interactions and risks: It shouldn’t be used by people with uncontrolled blood pressure, seizures, a history of anorexia or bulimia, people taking psychiatric drugs containing bupropion (Wellbutrin, Zyban), or individuals dependent on opioids or in withdrawal from drugs or alcohol. It can increase suicidal thoughts or actions.

Liraglutide (Saxenda)

This daily injected drug was approved by the FDA in 2014 for adults and in 2020 for children ages 12 and older with obesity.

How it works: It’s in a family of medicines known as glucagon-like peptide-1 (GLP-1) receptor agonists, which work by mimicking a hormone in the brain that regulates appetite and food consumption.

Common side effects: Nausea, diarrhea, constipation, abdominal pain, headache, and increased heart rate. Rare side effects include an increased risk of pancreatitis, and it’s been linked to thyroid tumors in animals.

Interactions and risks: In a smaller dose, liraglutide is used as a diabetes medication called Victoza, which should not be used in conjunction with Saxenda.

Phentermine-Topiramate (Qsymia)

This pill was approved by the FDA in 2012 for adults who are overweight or obese, and in 2022 for patients ages 12 and older with obesity.

How it works: This combination pill suppresses appetite and makes people feel full sooner.

Common side effects: Constipation, dizziness, dry mouth, tingling in hands and feet, brain fog or cognitive impairment, and difficulty sleeping.

Interactions and risks: It shouldn’t be used by people with glaucoma or hyperthyroidism, by women who are pregnant or breastfeeding, or by some individuals with a history of heart attack, stroke, heart rhythm disorders, kidney disease, or mood problems.

Orlistat (Xenical, Alli)

This pill was approved by the FDA in 1999 as a prescription weight loss drug (Xenical) and in 2007 at a lower dose for nonprescription use (Alli).

How it works: It works in the gut to limit the amount of fat absorbed from foods you eat.

Common side effects: Diarrhea, gas, stomach pain, and oily stool leakage.

Interactions and risks: It’s linked to rare cases of severe liver injury; dangerous interactions with cyclosporine, a drug to prevent organ transplant rejections; and the potential for malnutrition if patients don’t take a multivitamin.

 Orlistat has been shown to decrease the absorption of fat-soluble vitamins as well as some prescription medications, including Amiodarone (used to treat irregular heartbeats)and ciclosporin (used to treat inflammatory diseases like rheumatoid arthritis). Orlistat may also affect the dosage of warfarin, an anticoagulant.

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Felicia Ray Owens
Felicia Ray Owenshttps://feliciarayowens.com
Writer, founder, and civic voice using storytelling, lived experience, and practical insight to help people find balance, clarity, and purpose in their everyday lives.

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