Rising interest in the pharmacological treatment of obesity has increased significantly after 2012. The introduction of GLP-1 receptor agonists like Wegovy has caught the attention of the media. A study has shown a surge in online searches for GLP-1 receptor agonists since 2022.
This increased interest in pharmacological treatments for obesity reflects a growing recognition of the need for effective solutions to combat this widespread health issue. GLP-1 receptor agonists work by increasing feelings of fullness, leading to decreased food intake and potentially aiding in weight loss. The availability of newer medications like Wegovy offers additional options for individuals struggling with obesity and can serve as a valuable tool in conjunction with lifestyle changes.
Criteria for Weight Loss Medication Prescriptions
The evaluation of using weight management medications starts with the Body Mass Index (BMI). Most medications are prescribed to individuals with a BMI of 30 or higher, or a BMI of 27 or higher if there are health issues related to weight for that individual.
Zepond was approved in November 2023 for adults with a BMI of 30 or higher. In each case, the doctor and patient should discuss the current health issues of the patient, other medications being taken, and family medical history. The cost of the medication and potential side effects will also influence the decision.
Although some weight loss medications are only FDA-approved for adults, semaglutide, liraglutide, and orlistat are approved for children as young as 12 years old. All medications discussed here are contraindicated during pregnancy.
Currently Available Weight Loss Medications
Some weight management medications have been on the market for many years, with new ones constantly emerging. Commonly prescribed weight loss medications include:
Semaglutide (Wegovy, Ozempic)
Wegovy – the brand name for semaglutide, a GLP-1 receptor agonist. It was FDA-approved in 2021. It is taken as an injection and approved for use in adults and children aged 12 and older with obesity (BMI ≥30 in adults, BMI ≥95th percentile by age and sex in children) or in some adults with overweight (BMI ≥27) who also have weight-related health issues. The dose should be gradually increased over 16-20 weeks to a dosage of 2.4 mg. This gradual method can help alleviate side effects, including gastrointestinal symptoms, headaches, dizziness, and fatigue.
Rybelsus – the same medication but approved for the treatment of type 2 diabetes.
Tirzepatide (Zepbound, Mounjaro)
Tirzepatide was previously approved for the treatment of type 2 diabetes as Mounjaro. Like Zepond, it is approved for the treatment of obesity in adults with a BMI of 30 or higher.
It acts as both a GLP-1 and GIP receptor agonist, similar to semaglutide, working to reduce appetite and is meant to be used in conjunction with diet and exercise for weight loss. It is also administered as an injection.
Liraglutide (Saxenda)
Liraglutide is an injectable daily medication that affects hormones from the intestines, sending signals to the brain to make the patient feel full faster and reduce hunger signals. Starting doses range from 0.6 mg to 3 mg per day. Some patients may lose 5-10% of their weight, especially with increasing the dose of liraglutide.
Among the side effects are nausea, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, and renal failure. The medication is contraindicated in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2.
Phentermine, the oldest and widely used weight-loss drug, is now recommended for long-term treatment in addition to short-term use. Some patients can lose about 5% of their weight by taking phentermine.
In the USA, phentermine is almost exclusively available in the form of HCl in doses of 15 mg and 30 mg. Side effects include headache, overstimulation, increased blood pressure, insomnia, fast or irregular pulse, and tremors.
Interactions may occur during or up to 14 days after taking monoamine oxidase inhibitors (MAOIs), sympathomimetics, alcohol, adrenergic blocking agents, and possibly some anesthetic drugs.
Topiramate can be combined with phentermine to reduce appetite and cravings for food, especially in adults with migraines and obesity. Some patients can lose an average of 5-10% of their weight. If no more than 5% weight loss is achieved after 12 weeks of maximum dose, the intake of weight-loss pills should be gradually discontinued.
Daily doses in four dosages range from 3.75 mg/23 mg to 15 mg/92 mg. Side effects include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth. Contraindications include uncontrolled hypertension, coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants.
Naltrexone-bupropion combines an opioid receptor antagonist with an antidepressant, acting on brain areas responsible for pleasure and reward, thereby reducing cravings and appetite, with some patients losing 5-10% of their weight.
Start with a daily dose of one tablet of 8/90 mg and gradually increase to four tablets a day. The most common side effects are nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. This medication should not be prescribed to patients with epilepsy or those taking opioids for chronic pain.
Setmelanotide is an agonist of melanocortin-4 receptors, designed for chronic weight loss in adults and pediatric patients aged 6 and older with obesity due to rare genetic disorders. The condition should be confirmed by genetic testing showing pathogenic, likely pathogenic, or variants of uncertain significance (VUS) in the POMC, PCSK1, or LEPR genes.
Orlistat, an enzyme inhibitor available in capsule form, blocks an enzyme that breaks down fats from food, preventing the absorption of dietary fats, and is used in combination with a reduced-calorie diet to reduce the risk of weight regain. Some patients may lose about 5% of their weight. The dosage is one 120 mg capsule three times a day with each main meal containing fat (during or within 1 hour after eating).
A 60 mg capsule for each meal with fat is available over the counter. The most common adverse reactions to orlistat are oily spotting, flatulence with discharge, increased defecation, and fecal incontinence.
Plenity, approved by the FDA in 2019, is a medical device, not a drug, for people with a BMI of 24 to 40. It consists of a capsule that releases a biodegradable, superabsorbent hydrogel into the stomach, helping to enhance satiety and allowing a person to consume less food. The average weight loss in real studies is 9%.
For more information on each of the weight-loss drugs, refer to the latest issue of the “Obesity Algorithm” from the Obesity Medicine Association.
With increasing consumer interest in weight-loss medications and the rise in obesity, new drugs will appear on the market in the coming years. Lilly is developing orphalipron, an oral GLP-1 inhibitor. Retatruitide, another injectable targeting GLP-1, GIP, and glucagon. Pfizer is also developing two GLP-1 inhibitors that can be taken as tablets. Meanwhile, Amgen is conducting trials for a drug candidate that is both a GLP-1 receptor agonist and a GIP receptor antagonist, unlike a dual agonist, such as semaglutide.
Researchers continue to search for hormones such as peptide YY that play a role in appetite for other ways to combat obesity through drug therapy.
In 2021, in an interview with Endocrine News, Robert Kushner, a professor at Northwestern Medical School, welcomed the “new direction we are taking in the treatment of obesity, viewing it as an endocrine disease, treating it hormonally ..,” providing patients and providers with different options for the most effective treatment.
The treatment of obesity requires finding the best combination of treatments that work best for each individual. In 2022, the American College of Gastroenterology published recommendations for the use of weight-loss drugs among patients with obesity who do not respond adequately to lifestyle modifications. They proposed four main options:
– Semaglutide
– Liraglutide
– Phentermine-topiramate extended-release (ER)
– Naltrexone-bupropion extended-release (ER)
Phentermine and diethylpropion were also recommended. It should be noted that these recommendations were made before the approval of Zepbound.
Weight management medications primarily work by regulating hormones in the brain, digestive system, and adipose tissue to suppress appetite, cravings, and promote satiety.
Some medications are taken orally, and others are administered as subcutaneous injections. When patients inquire about weight-loss pills versus injections, they usually mean the two options for GLP-1 RAs. Data published separately by Novo Nordisk and Pfizer in May 2023 showed that tablets and injections are roughly equally effective.
Many medications can contribute to obesity or cause weight gain. The following drugs may potentially cause changes in weight in some individuals:
– Some beta-blockers and calcium channel blockers
– Anti-diabetic medications, such as insulins, sulfonylureas, thiazolidinediones, and meglitinides
– Hormonal medications, such as glucocorticoids and injectable progestins
– Antiepileptic medications, including carbamazepine, gabapentin, valproate, and pregabalin
– A variety of antidepressants
– Some mood stabilizers
– Migraine medications, such as amitriptyline and paroxetine
– Some antipsychotics
– Chemotherapeutic and anti-inflammatory agents
An obesity treatment plan may include several forms of treatment, including medications, diet, exercise, or surgery. All weight-loss medications work best in the context of a healthy diet and exercise. Even when patients exercise and make lifestyle changes, medications can help with appetite, cravings, and metabolism.
Some weight management medications are intended for short-term use, while others are for long-term use. For example, some are FDA-approved for up to 12 weeks.
Those approved by the FDA for long-term use include orlistat (Xenical, Alli), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy, Ozempic), and tirzepatide (Zeplound, Moundjaro).
For some of them, there is a lengthy dose escalation period of up to five months to reach the full dose. Keep in mind that obesity is a disease, and no medication can definitively “cure” it.
While GLP-1 RAs have attracted much attention, they are just the latest in a long history of weight-loss drug development. A 2022 article in the Life Science journal explains that researchers are looking for more effective ways to combat obesity through hormonal therapy.
In a 2022 interview with Endocrine News, Robert Kushner, a professor at Northwestern Medical School, welcomed “the new direction we are taking in the treatment of obesity, viewing it as an endocrine disease, treating it hormonally ..,” providing patients and providers with different options for the most effective treatment.
Obesity management requires the consideration of the best treatment combination that works best for each individual.
“Due to the discovery of more physiological weight gain mechanisms, medications targeting newly discovered receptors and/or enzymes with improved safety profiles and fewer psychological side effects have been introduced. Additionally, medications targeting appetite or satiety signaling have been actively studied and have shown increased interest from physicians. Research has also been conducted on medications targeting metabolic tissues – such as adipose tissue or muscles – to promote weight loss, but as of today, nothing has advanced into clinical practice.”
Undoubtedly, new candidates will continue to be developed, and some of them will enter the market.
As with any medications, some weight loss drugs have been on the market longer, have generic alternatives, and are more affordable. GLP-1 RAs are known for their high cost. The Kaiser Family Foundation estimates Wegovy’s annual expected price at $13,600. According to GoodRx, phentermine can be purchased for just $10.
The description varies, and it will influence many patients when choosing weight loss medications. Medicaid does not cover weight loss medications.
AOMs can counteract the effects of metabolic adaptation and prevent weight gain. After weight loss, the body undergoes metabolic adaptation, which often leads to increased appetite hormones and decreased satiety hormones and basal metabolic rate, together contributing to weight gain. If a patient has achieved clinically significant weight loss with obesity medications and if the physician and patient believe that the medication helps prevent weight gain, a weight loss plateau should not be a reason to discontinue the medication, but rather the medication should be continued to maintain weight loss.
The only over-the-counter weight loss drug currently approved by the FDA is Alli (orlistat). Other over-the-counter products are considered supplements. They are not regulated by the FDA and do not have proper studies confirming their safety and effectiveness.
With prescription medications, a healthcare provider may weigh all factors affecting the patient’s lifestyle and BMI, as well as monitor progress and side effects. These relationships may allow for dose adjustments or medication switches if one seems more suitable for the patient.
Many antidepressants have a positive impact on weight (causing weight gain), some are weight-neutral, and at least one has a negative impact on weight (causing weight loss).
Antidepressants are divided into categories: selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and others. Drugs in each of these categories can cause weight gain.
Among SSRIs, Paroxetine shows the greatest associated weight gain. Other SSRIs, including Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), and Sertraline (Zoloft), have different effects on weight, and some do not cause weight gain for up to six months of use.
Weight-gaining drugs in the tricyclic antidepressant group include Amitriptyline, Doxepin, and Imipramine. Desipramine, Nortriptyline, and Protriptyline have varying effects on weight.
Bupropion (Wellbutrin), an aminoketone, is considered weight-neutral and is prescribed for weight loss as well as for treating depression. However, people react differently to antidepressants.
The following FDA-approved medications suppress appetite: Tirzepatide (Zeposia), Liraglutide (Saxenda), Naltrexone-Bupropion (Contrave), Phentermine-Topiramate (Qsymia), as well as these stimulants: benzphetamine (Didrex™), diethylpropion (Tenuate™), phentermine (Adipex-P, ProFast), and phendimetrazine. Each drug affects appetite differently.
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