The quest for effective weight management solutions has led to the development of various prescription medications. While these drugs can be helpful in promoting and maintaining weight loss as part of a comprehensive obesity treatment plan, they also come with potential side effects that patients and prescribers need to be aware of. This article explores the benefits, side effects, and important considerations associated with commonly used weight loss drugs.
The Rise of Weight Loss Medications
For many years, patients struggling with weight loss were told that success simply required more willpower - eat less, exercise more and the weight would eventually come off. But recent advances in medical science prove it’s often not that simple. Recent advances in medical science prove it’s often not that simple. “We now know significantly more about the chemical and structural changes that occur with excess body weight,” says Leena Khaitan, MD, bariatric surgeon and Director of the Metabolic and Bariatric Nutrition Center at University Hospitals. Prescription drugs are medicines that a health care provider prescribes for you. Your health care provider may suggest a weight-loss drug for you in some cases. Before choosing a medicine for you, your health care provider thinks about your history and health challenges. These drugs aren't for everyone. Prescription weight-loss drugs that you can use for more than 12 weeks, called long-term use, lead to major weight loss compared with an inactive treatment that doesn't use medicine, called a placebo. Taking these drugs for a year can mean a loss of total body weight of 3% to 12% more than that lost with lifestyle changes alone. That may not seem like a lot. But losing 5% to 10% of your total weight and keeping it off can have important health benefits.
Understanding GLP-1 Agonists
GLP-1 drugs, also called GLP-1 agonists, are shortened names for glucagon-like peptide-1 receptor agonists. GLP-1 is a hormone that your small intestine makes. It has several roles, including:
- Triggering insulin release from your pancreas: Insulin is an essential hormone that allows your body to use the food you eat for energy. It lowers the amount of glucose (sugar) in your blood. If you don’t have enough insulin, your blood sugar increases, leading to diabetes.
- Blocking glucagon secretion: Glucagon is a hormone your body uses to raise your blood sugar levels when necessary. So, GLP-1 prevents more glucose from going into your bloodstream.
- Slowing stomach emptying: Slower digestion means that your body releases less glucose (sugar) from the food you eat into your bloodstream.
- Increasing how full you feel after eating (satiety): GLP-1 affects areas of your brain that processes hunger and satiety. GLP-1 agonist medications work by mimicking this hormone. In medication terms, an agonist is a manufactured substance that attaches to a cell receptor and causes the same action as the naturally occurring substance. In other words, GLP-1 medications bind to GLP receptors to trigger the effects (or roles) of the GLP-1 hormone. The higher the dose of the GLP-1 agonist, the more extreme the effects.
When you eat, your digestive system breaks carbohydrates down into simple sugars that travel through your bloodstream. GLP-1 triggers the release of insulin from your pancreas. In people with type 2 diabetes, the body's cells are resistant to the effects of insulin, the body does not produce enough insulin, or both. These drugs also act in the brain to reduce hunger and act on the stomach to delay emptying, so you feel full for a longer time. These effects can lead to weight loss, which can be an important part of managing diabetes. More recently, the FDA has approved several GLP-1 agonists for weight loss in people with obesity who do not have diabetes. Ten GLP-1 drugs are FDA-approved to treat either type 2 diabetes or weight loss. Examples such as Wegovy and Ozempic are relatively new additions to the weight loss toolbox. Their promise of 15-20 percent weight loss is enticing to those who haven’t had success with diet and exercise alone,” says Dr. Khaitan. GlP-1 agonists help lower blood sugar levels.
Eligibility and Usage
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. Weight loss drugs may be an option for adults up to age 75. They are not recommended for children, women who are pregnant or breastfeeding and those with certain health conditions like liver or kidney problems.
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Common Weight Loss Medications and Their Side Effects
Here we will look at the side effects of phentermine with and without topiramate, naltrexone-bupropion, liraglutide, semaglutide, orlistat, and tirzepatide.
Phentermine: The oldest and most widely used weight loss medication is phentermine. It has been around since 1959 and has been used in combination with topiramate since the 1990s. Phentermine works at the brain level to decrease hunger. 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. The dose is taken once daily in the morning; avoid an evening dose as it may keep you awake. As these medicines are amphetamine-related, drug dependence, abuse or withdrawal may occur with long-term use. Stimulants are classified as controlled substances.
Phentermine combined with topiramate: Phentermine combined with topiramate cannot be taken during pregnancy. The benefit of this combination is that two medications are working together to decrease hunger and increase fullness. Side effects of taking phentermine-topiramate include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth. Contraindications include uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants. Tingling or numbing sensation (paresthesias), dizziness, altered taste, insomnia (difficulty sleeping), constipation, dry mouth. 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.
Naltrexone-bupropion: Naltrexone-bupropion is another combination medication that can help with fullness and cravings. A person should not take this medication if they have a seizure disorder or take opioids for chronic pain. The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. Contrave side effects can include constipation, dizziness, headache, trouble sleeping, and upset stomach. Bupropion is an antidepressant medicine and naltrexone is usually given to block the effects of narcotics or alcohol in people with dependence. Bupropion-naltrexone can raise blood pressure. So your provider will need to check your blood pressure regularly at the start of treatment. Like all antidepressants, bupropion carries a warning about suicide risk. 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.
Liraglutide and Semaglutide: Liraglutide and semaglutide are both injectable, although oral forms of both are approved to treat type 2 diabetes. Liraglutide is injected daily and semaglutide, weekly. Gastrointestinal issues are the most common complaint among people who are just starting semaglutide. 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. Saxenda is a glucagon-like peptide-1 (GLP-1) receptor agonist first approved in Dec. 2014. It 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. Wegovy is also approved to help protect the heart.
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Orlistat: Orlistat is a lipase inhibitor that works by blocking the enzyme that breaks down fats consumed through food, thereby inhibiting the absorption of dietary fats. The undigested fat is then passed through the body. 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. Orlistat can cause side effects such as passing gas and having loose stools. You need to follow a low-fat diet when taking this medicine. In rare cases, people have had serious liver injury with orlistat. Xenical, the prescription form of orlistat, was first FDA-approved in 1999. Xenical was followed by the lower dose, over-the-counter (OTC) orlistat (alli) in 2007.
Tirzepatide: Tirzepatide was initially approved to treat type 2 diabetes. In 2023, it was approved for weight loss. As a GLP-1 and GIP receptor agonist, it increases feelings of fullness and helps people maintain a more restrictive diet. 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.
Managing Gastrointestinal Side Effects of GLP-1 Agonists
With the right strategies and a well-informed approach, managing these side effects is possible. You too can achieve a successful voyage towards a healthier weight. Nearly half of the people who take a GLP-1 weight management medication experience one or more GI side effects. The most commonly reported ones are nausea and vomiting, acid reflux, bloating, stomach cramps, diarrhea and/or constipation. While these symptoms are generally mild and temporary, they may make it difficult to stick with the treatment. Most of these medications are prescribed at a lower dose and adjusted slowly over time to help your body adjust. Symptoms typically decrease as your body adapts to the medication and your eating habits change. Side effects may resolve initially but could occur again with a dose increase. To get started on the right path, here are some general tips for minimizing these side effects.
Food Choices
Limiting high fat and greasy foods that take longer to digest can minimize nausea and cramping. Limiting concentrated sweet foods and sugary beverages will also help reduce side effects. To help reduce acid reflux, limit spicy foods and choose bland foods that are easily tolerated, especially if you have been having more episodes of reflux. If you have constipation, don’t forget to include high fiber foods like fruits, vegetables, legumes and whole grains. Finally, remember to stay hydrated by drinking plenty of water!
Portion Sizes
When you start taking GLP-1 medications, you will likely begin to feel full much sooner than usual when eating a meal. This is the intended effect of the medication, but it can take time to get used to. Start out by serving yourself and eating smaller portions. Listen to your body when it starts to feel full so that you don’t feel nauseated after eating. When possible, eat on smaller plates and bowls to help you visualize a smaller meal. If you are at a restaurant, ask for an empty container when ordering and put some of your meal in the container when it arrives. Or keep portions in check by ordering healthy appetizers, soups, salads or sides from the menu.
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Listen to Your Body
Get in touch with your body’s signs of fullness and stop eating at the first sign of fullness. You may find that eating small, frequent meals will help you get enough protein and calories. While reduced appetite is often a desired effect, it’s crucial to still meet your daily nutritional needs. Pay attention to the number of hours between meals since your body may not give you hunger cues to eat. If you are feeling nauseated, drinking unsweetened ginger or peppermint tea may help.
Prioritize Adequate Nutrition
Even if you aren’t feeling hungry, it’s important to still consume healthy nutrients to preserve muscle mass and lean body mass. While it is best to get nutrition through whole foods, a protein drink can help provide your body with nutrients without making you feel nauseous. It can be an easy alternative when you are short on time or unable to eat a meal. Some options include:
- Ensure® Max Protein
- Glucerna® Protein Smart
- Premier Protein®
- Muscle Milk®
- Fairlife® Protein
Other Side Effects and Considerations
Ozempic Face
Among those side effects is "Ozempic face," where skin on the face sags and wrinkles. If weight is lost in a more gradual way, these changes may not be as noticeable.
Mental Health
Headlines have warned of increased suicidal ideation associated with semaglutide. Like all antidepressants, bupropion carries a warning about suicide risk.
Surgical Considerations
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. This can occur because these medicines can slow down gastric emptying.
Long-Term Use and Weight Regain
A 2023 analysis found that 68% of people taking semaglutide or liraglutide for weight loss stopped within a year. That population may have stopped for a variety of reasons, including side effects, cost coupled with lack of insurance coverage, or simply shortages of the medications. In the study above, 4.5% of users stopped the drugs due to side effects. It is very likely that after stopping weight loss medications there will be some weight regained. Obesity is a chronic disease like hypertension and when the medications are stopped, the condition returns. However, if lifestyle modifications like calorie restriction, healthy eating, regular exercise and other behavioral changes are maintained, it’s unlikely that weight will return to its original level.
Interactions with Other Medications
Yes, weight loss drugs can interact with other medications, supplements and herbal products. As some of these interactions can be dangerous, always tell your doctor about all the medications and supplements you take before starting weight loss drugs.
Cost and Insurance Coverage
Weight-loss drugs can be expensive and aren't always paid for by insurance. Insurance coverage for weight loss drugs varies widely depending on the specific plan, the type of drug, and the patient's medical history. Commercial providers may require that a patient have a certain body mass index (BMI) and/or an obesity-related health condition like type 2 diabetes or heart disease. Others may require that the patient has tried other weight loss methods like diet and exercise before they will cover weight loss drugs. 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.
The Importance of a Comprehensive Approach
“Research shows that losing just 5-10 percent of body weight can dramatically improve your health, so losing those extra pounds offers more than just a cosmetic reward. But are these medications safe? Do they have side effects? Significant weight loss is never easy and there is no such thing as a magic bullet for weight loss. It takes permanent lifestyle changes, including diet and exercise, and patience to allow these changes to become a habit. “Losing weight is an intentional effort. Avoiding processed foods that are calorie-dense but nutrient deficient and healthy lifestyle choices are essential to achieve a healthy weight,” says Dr. Khaitan. All these approaches may incorporate the use of weight loss drugs to supplement and support healthy weight loss. 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 and understand it will take time and discipline for permanent results.
A Word of Caution Regarding "All-Natural" 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.