Weight loss medications can be a helpful tool as part of a comprehensive obesity treatment plan to assist patients in losing weight and maintaining the loss. However, it's essential to help patients consider the pros and cons to find the right fit for them because these medications can have potential side effects. It will take time and discipline for permanent results, so be sure to talk to your doctor for sound advice before starting any weight loss program.
Types of Weight Loss Medications
Several prescription weight loss drugs are available, each working through different mechanisms. The latest prescription drugs, like Zepbound, Wegovy and Saxenda are approved for chronic (long-term) weight loss and come as subcutaneous (under the skin) injections. Up to a 20% weight loss or more has been seen with these newer treatments. Prescription weight loss drugs such as phentermine and topiramate (Qsymia), bupropion and naltrexone (Contrave) are used for chronic, long-term weight loss, but only if adequate results occur. Orlistat (alli, Xenical) can be used for longer-term weight loss, including the maintenance of previously lost weight. Weight loss medications should be used alongside a low calorie diet and a doctor-approved exercise plan for best results.
Here's a breakdown of some common medications:
GLP-1 Agonists and GLP-1/GIP Agonists: GLP-1 (glucagon-like peptide-1) drugs, also called GLP-1 agonists, and GLP-1/GIP medications, like Zepbound, Wegovy and Saxenda, are effective tools for helping people lose weight and manage obesity. These medications mimic your natural gut hormones that regulate blood sugar, slow stomach emptying, and suppress appetite. Saxenda is a glucagon-like peptide-1 (GLP-1) receptor agonist first approved in Dec. 2014 and is used in addition to diet and exercise for long-term weight management in adults who are obese (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/m2) with other weight-related medical issues. The Victoza brand of liraglutide contains the same active ingredient as Saxenda but is used to treat type 2 diabetes. Newer prescription weight loss drugs like Wegovy or Zepbound can produce dramatic weight loss results of at least 20%, but come with a initial risk of stomach-related side effects, like nausea, vomiting, diarrhea or stomach-area pain. In November 2024, the FDA updated the warnings for all GLP-1 agonist and GLP-1 / GIP agonist medicines to note that these agents can increase the risk of food or liquid getting into your lungs (called pulmonary aspiration) during procedures or surgery while you are under deep sedation or general anesthesia because these medicines can slow down gastric emptying.
Phentermine: The oldest and most widely used weight loss medication is phentermine. It has been around since 1959 and works at the brain level to decrease hunger.
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Qsymia (phentermine and topiramate): Prescription weight loss drugs such as phentermine and topiramate (Qsymia) are used for chronic, long-term weight loss, but only if adequate results occur. Phentermine suppresses the appetite similar to an amphetamine stimulant, while topiramate is used a medication to control seizures.
Contrave (bupropion and naltrexone): Prescription weight loss drugs such as bupropion and naltrexone (Contrave) are used for chronic, long-term weight loss, but only if adequate results occur. Bupropion is an antidepressant medicine, and naltrexone is usually given to block the effects of narcotics or alcohol in people with dependence.
Orlistat (Alli, Xenical): Orlistat (alli, Xenical) can be used for longer-term weight loss, including the maintenance of previously lost weight. Xenical, the prescription form of orlistat, was first FDA-approved in 1999, followed by the lower dose, over-the-counter (OTC) orlistat (alli) in 2007.
Common Side Effects
Side effects of drugs used for weight loss may vary depending upon the type of drug you take and how the drug works. Weight loss drugs can be associated with important or serious side effects, and some may have the potential for dependence and abuse.
Here's a look at the side effects of phentermine with and without topiramate, naltrexone-bupropion, liraglutide, semaglutide, orlistat, and tirzepatide.
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GLP-1 Agonists (Semaglutide, Liraglutide): Gastrointestinal issues are the most common complaint among people who are just starting semaglutide. The side effects that many people cite as their reason for quitting are digestive ones, including nausea, vomiting, and upset stomach. For this reason, many patients start at a lower dose and work up to their eventual dose. Headlines have warned of increased suicidal ideation associated with semaglutide. The JAMA study mentioned above compared GLP-1 agonists against naltrexone-bupropion. Researchers concluded that the use of the GLP-1 agonists was associated with an increased risk of pancreatitis, bowel obstruction, and gastroparesis. GLP-1 drugs for diabetes and weight loss have proven to be very effective, but they do have side effects. Among those side effects is "Ozempic face," where skin on the face sags and wrinkles. Most side effects of GLP-1 drugs are not serious.
Phentermine: Side effects include headache, overstimulation, high blood pressure, insomnia, rapid or irregular heart rate, and tremor. 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. Increased blood pressure and heart rate, insomnia, nervousness, restlessness, dependence, abuse or withdrawal may occur with long-term use. Stimulants are classified as controlled substances, and as these medicines are amphetamine-related, drug dependence, abuse or withdrawal may occur with long-term use. Amphetamine-derivative, stimulant type weight loss drugs may be associated with constipation, dry mouth, restlessness, withdrawal effects, or insomnia (difficulty falling asleep), drug abuse and addiction.
Qsymia (phentermine and topiramate): Side effects of taking phentermine-topiramate include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth. Tingling or numbing sensation (paresthesias), dizziness, altered taste, insomnia (difficulty sleeping), constipation, dry mouth. The dose is taken once daily in the morning; avoid an evening dose as it may keep you awake. Qsymia has restricted access because one of its active ingredients known as topiramate may cause severe birth defects in pregnant women. Do not use Qsymia if you are pregnant or planning a pregnancy. Contraindications include uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants.
Contrave (bupropion and naltrexone): Contrave side effects can include constipation, dizziness, headache, trouble sleeping, and upset stomach. The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. Do not use Contrave with other bupropion-containing products (such as Wellbutrin SR, Wellbutrin XL, Aplenzin) as it may increase the risk of severe side effects.
Orlistat (Alli, Xenical): Side effects of orlistat can be unpleasant: oily spotting, gas, stomach pain, fecal urgency or incontinence, soft stools, and the possibility of serious liver injury can occur. Lipase inhibitors such as alli or Xenical (orlistat) can cause oily spotting, gas, stomach pain, fecal urgency or incontinence, soft stools, and the possibility of serious liver injury.
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Tirzepatide: Common side effects include constipation, upset stomach, bloating, and diarrhea. Potential serious side effects also include stomach problems, kidney problems or failure, gallbladder problems, pancreatitis, or hypoglycemia, among others.
Important Considerations
Eligibility: Eligibility for weight loss medications is typically based on body mass index (BMI). For semaglutide or liraglutide, a patient must must be an adult or child age 12 or more, with a BMI of 30 or greater or with a BMI of 27 or greater with comorbidities such as high blood pressure, diabetes, or high cholesterol. People who have a BMI of 30 or above do not need to have a chronic disease associated with their BMI, because obesity is considered a chronic disease. Requirements are similar for many other weight loss medications, including phentermine, naltrexone-bupropion, and orlistat, although not all are FDA-approved for use in children. The more recently approved tirzepatide is approved only for adults with a BMI of 30 or greater.
Discontinuation: A 2023 analysis found that 68% of people taking semaglutide or liraglutide for weight loss stopped within a year. In the study above, 4.5% of users stopped the drugs due to side effects. Because stopping one of these medications comes with a high risk of weight regain, a person taking them should understand the risks.
"All-Natural" or "Herbal" Supplements: If you are interested in losing weight, you may have considered buying an "all-natural" or "herbal" diet weight loss product, also called a weight loss dietary supplement, at the store or from the Internet. Chromium, Green Tea extract, Hoodia, and Guar Gum are some of the herbal dietary supplements available on the market today that claim to help with weight loss. These products may claim to "magically melt" fat away and seem like an easy fix to shed a few pounds. Federal regulators have warned that many of these marketed dietary supplements aren’t effective and may even cause serious side effects. It’s important to know that over-the-counter (OTC) dietary supplements are not reviewed or approved by the FDA. The FDA does investigate herbal supplements if they appear to be causing harm. Many examples exist of recalled dietary supplements used for weight loss and other conditions. In 2004 the FDA removed dietary products with the stimulant ephedra completely from the market due to severe side effects such as heart attack, stroke and seizures.
Managing Side Effects
GLP-1 and GLP-1/GIP medications, like Zepbound, Wegovy and Saxenda, are effective tools for helping people lose weight and manage obesity. While these medications effectively support weight loss, they can have potential side effects.
Here are some tips for managing the side effects:
- Eat slowly: Eating slowly gives you time to recognize when you feel full.
- Increase your fiber intake: Add fiber-rich fruits, vegetables, whole grains, beans and other legumes.
- Stay hydrated: Drink 64 ounces of water daily to maintain bowel regularity.
- Talk to your doctor about a stool softener: If constipation persists, your doctor may recommend an over-the-counter stool softener or fiber supplement.
- Avoid irritants: Limit your intake of greasy or spicy foods and carbonated beverages, which may trigger indigestion.
- Time your meals: Avoid eating three hours before bed. Staying upright gives your food more time to digest.
- Focus on eating nutrient-dense foods: Choose nutritious, low-calorie foods such as lean proteins, healthy fats, fruits, vegetables, and whole grains.
- Eat proteins first to maintain your muscle mass while losing weight.
- Consider protein shakes: While most of your diet should come from whole foods, your dietitian may talk to you about using a protein supplement until your appetite improves.
Contraindications and Warnings
- Pregnancy: Phentermine combined with topiramate cannot be taken during pregnancy. Qsymia has restricted access because one of its active ingredients known as topiramate may cause severe birth defects in pregnant women. Do not use Qsymia if you are pregnant or planning a pregnancy.
- Bupropion Interactions: Do not use Contrave with other bupropion-containing products (such as Wellbutrin SR, Wellbutrin XL, Aplenzin) as it may increase the risk of severe side effects.
- Surgical Procedures: In addition, tell your doctor that you take GLP-1 drugs if you are having surgery or a procedure that involves general anesthesia. In November 2024, the FDA updated the warnings for all GLP-1 agonist and GLP-1 / GIP agonist medicines to note that these agents can increase the risk of food or liquid getting into your lungs (called pulmonary aspiration) during procedures or surgery while you are under deep sedation or general anesthesia because these medicines can slow down gastric emptying.
- Other Contraindications for Phentermine/Topiramate: Contraindications include uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants.
The Importance of Medical Supervision
This is not a complete list of all common or serious side effects. There are other potentially serious side effects. This is not all the information you need to know about weight loss drugs or their side effects for safe and effective use and does not take the place of your doctor’s directions. Weight loss medications should be used alongside a low calorie diet and a doctor-approved exercise plan for best results. Be sure to talk to your doctor for sound advice before starting any weight loss program. If a patient is hesitant to try a certain medication due to concerns about side effects, you may wish to prescribe an alternative, as there are many options available that target different mechanisms of hunger, fullness, and weight loss. If you are a provider prescribing a weight loss medication, or you’re someone considering asking your doctor about a weight loss medication, familiarize yourself with the potential side effects. As medications are on the market longer, knowledge of their side effects increases.
Financial Considerations
At this time, most insurance plans in the US do not cover medications to treat overweight and obesity. Manufacturers may offer copay card assistance, especially with the newer agents like Zepbound or Wegovy, which may help to save you money if you have commercial insurance.