Les meilleurs médicaments pour perdre du poids

L’avènement des agonistes des récepteurs du peptide-1 apparenté au glucagon (agonistes des récepteurs du GLP-1), sous des noms commerciaux comme Wegovy et Ozempic, a suscité une attention médiatique explosive. Selon une étude publiée en 2022 dans Frontiers in Cardiovascular Medicine , les recherches en ligne et les prescriptions d’agonistes des récepteurs du GLP-1 augmentent parallèlement.

Avec un choix plus large de médicaments amaigrissants, les patients peuvent se demander quel est le médicament sur ordonnance le plus puissant ou le plus efficace. La réponse est complexe. Il n’est pas toujours facile de déterminer le médicament le plus adapté à un individu. Le marché évolue rapidement ; il est donc important de se tenir au courant des options disponibles, de leurs avantages et de leurs inconvénients.

Critères de prescription de médicaments pour la perte de poids

Pour déterminer si une personne est admissible à un traitement amaigrissant, il faut d’abord évaluer son IMC . La plupart des médicaments sont prescrits aux personnes dont l’ IMC est supérieur ou égal à 30, ou supérieur ou égal à 27 si elles présentent des problèmes de santé liés au poids .

Zepbound a été approuvé en novembre 2023 pour les adultes ayant un IMC de 30 ou plus. Pour chaque cas, le médecin et le patient doivent discuter des problèmes de santé actuels du patient, de ses autres médicaments et de ses antécédents médicaux familiaux. Le coût et les effets secondaires du médicament influenceront également la décision.

Bien que certains médicaments amaigrissants soient approuvés par la FDA uniquement pour les adultes, le sémaglutide, le liraglutide et l’orlistat sont autorisés pour les enfants de 12 ans et plus. Tous les médicaments mentionnés ici sont contre-indiqués pendant la grossesse.

Médicaments pour la perte de poids actuellement disponibles

Certains médicaments amaigrissants sont sur le marché depuis de nombreuses années, et de nouveaux médicaments apparaissent fréquemment. Parmi les médicaments amaigrissants couramment prescrits, on trouve :

Sémaglutide (Wegovy, Ozempic)

Wegovy is a brand name for semaglutide, a GLP-1 receptor agonist. It was FDA approved in 2021. It is administered as an injection and approved for use in adults and children aged 12 years or more with obesity (BMI ≥30 for adults, BMI ≥ 95th percentile for age and sex for children) or some adults with excess weight (BMI ≥27) (overweight) who also have weight-related medical problems. The dose must be increased gradually over 16 to 20 weeks to arrive at the 2.4 mg dosage. This progression can help to alleviate side effects, which include gastrointestinal symptoms, headache, dizziness, and fatigue.

Ozempic is the same medication but is approved to treat type 2 diabetes.

Tirzepatide (Zepbound, Mounjaro)

Tirzepatide was previously approved to treat type 2 diabetes as Mounjaro. As Zepbound, it is approved to treat obesity in adults with a BMI of 30 or greater.

It is both a GLP-1 and a GIP receptor agonist and, like semaglutide, works by reducing appetite and is meant to be used in combination with diet and exercise to lose weight. It is also administered as an injection.

Liraglutide (Saxenda)

Liraglutide is a daily injectable medication that acts on hormones from the gut that send signals to the brain to make the patient feel full quicker and decrease hunger signals. Doses start at 0.6 mg to 3 mg a day. Some patients may lose 5–10% of body weight, especially with the liraglutide higher dose.

Side effects include nausea, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, and renal insufficiency. It is contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2.

Phentermine (Adipex, Suprenza)

Phentermine is the oldest and most widely used weight loss medication. It was originally used as a short-term medication to jump-start weight loss, but now newer medical guidelines have added it to long-term therapy. Some patients may lose about 5% of their body weight by taking phentermine.

In the US, phentermine is almost exclusively available in the HCl formulation – available in 15 mg and 30 mg strength. 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.

Phentermine-topiramate (Qsymia)

Topiramate can be combined with phentermine to decrease appetite and cravings. Having the combination of two drugs increases efficacy.

Adults with migraines and obesity are good candidates for this weight-loss medication. Some patients may lose an average of 5–10% of body weight.

If more than 5% weight loss is not achieved after 12 weeks of the maximum dose, the weight loss pill should be gradually discontinued.

Daily doses with four strengths start at 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 and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants.

Naltrexone-bupropion (Contrave)

Naltrexone-bupropion combines an opioid receptor antagonist with an antidepressant to affect the pleasure-reward areas of the brain and thereby decrease cravings and appetite. Some patients may lose 5–10% of body weight.

Start with a daily dose of one 8/90 mg tablet and gradually increase to four tablets a day. The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. This medication should not be prescribed to a patient who has a seizure disorder or who takes opioids for chronic pain.

Setmelanotide (Imcivree)

Setmelanotide is a melanocortin-4 receptor agonist indicated for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to one of several specific rare genetic disorders.

The condition must be confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of a variant of uncertain significance (VUS).

Orlistat (Xenical and Alli)

Orlistat is a lipase inhibitor that comes in a capsule and works by blocking the enzyme that breaks down fats consumed through food. In this way, it inhibits the absorption of dietary fats.

Undigested fat is then passed through the body. It is intended for use in conjunction with a reduced-calorie diet and is also indicated to reduce the risk of weight regain.

Some patients may lose about 5% of their body weight. Dosage is one 120 mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

An over-the-counter formulation is available at 60 mg capsule with each meal containing fat. The most common adverse reactions to orlistat are oily discharge from the rectum, flatus with discharge, increased defecation, and fecal incontinence.

Hydrogel (Plenity)

A medical device rather than a medication, Plenity was FDA-cleared in 2019 for people with a BMI of 24 to 40. The treatment has experienced increased media attention since the rise of GLP-1 receptor agonists.

It consists of a capsule that releases a biodegradable, super-absorbent hydrogel into the stomach. The gel helps to increase satiety, enabling the person to eat less. The average weight loss in real-world studies is 9%.

Upcoming Weight Loss Medications

With fervent consumer demand for weight loss medications, combined with rising obesity rates, more medications are bound for the market in the coming years.

Lilly is developing orforglipron, an oral GLP-1 inhibitor. Retatrutide, another injectible, targets GLP-1, GIP, and glucagon. Pfizer is also developing two GLP-1 inhibitors that can be administered as pills. Meanwhile, Amgen is trialing a drug candidate that is both a GLP-1 receptor agonist and a GIP receptor antagonist, as opposed to a dual agonist like semaglutide.

Researchers continue to seek hormones that play a role in appetite, such as peptide YY, for other ways to target obesity with medication.

Interviewed by Endocrine News in 2021, Robert Kushner, MD, a professor at the Northwestern University Feinberg School of Medicine, lauded “the new direction that we are going in obesity treatment, treating it more as an endocrine disease, treating it hormonally…”—giving patients and providers different options to choose the drug that will be the most useful.

Monoclonal antibodies are another “hot” category in drug development for a range of diseases, including obesity. For example, the monoclonal antibody bimagrumab is being studied as an infusion to increase muscle mass while decreasing fat.

With more options available, doctors will be increasingly able to personalize treatments as they match patients to the medications that will work best for them. For more information on these new options, enroll in OMA’s course on Future Advances in Anti-Obesity Medications.

Frequently Asked Questions About Weight Loss Medications

How effective are weight loss medications?

FDA-approved anti-obesity medications (AOMs) are safe, evidence-based therapies that target specific physiology to improve the disease and are most effective when they are used as part of a comprehensive treatment plan. The amount of weight a person loses depends on the medication they take, their overall health, and other individual factors.

Even as the range of weight loss medications has expanded, some drugs have been withdrawn based on their lack of efficacy as well as safety concerns.

What is the strongest weight loss prescription medication?

The amount of weight loss possible with semaglutide, according to clinical studies, is significant. A 2022 study of 175 individuals showed 5.9% weight loss at three months and 10.9% at six months. A larger study published in the New England Journal of Medicine showed even greater average loss—14.9%. However, drawbacks of semaglutide include high cost, side effects, and the long-term to indefinite length of treatment.

As with all obesity treatment, a person might experience better results with one medication over another. Each person, in partnership with their doctor, should try to find the right combination of treatments that work best for them.

In 2022, The American Gastroenterological Association released recommendations for weight loss medications among patients with obesity who do not respond adequately to lifestyle interventions alone. They listed four first-line options:

• Semaglutide

• Liraglutide

• Phentermine-topiramate extended-release (ER)

• Naltrexone-bupropion extended-release (ER)

They also recommended phentermine and diethylpropion. Note that these recommendations were made before the approval of Zepbound.

How do weight loss medications work?

They work primarily by regulating hormones in the brain, digestive system, and adipose tissue to suppress appetite and cravings and promote satiety.

Some medications are administered orally and others as subcutaneous injections. When patients ask about weight-loss pills vs. injections, they tend to refer to the two options for GLP-1 RAs. Data released in May 2023, separately by Novo Nordisk and Pfizer, stated that pills and injections are about equally effective.

Are there medications that can cause weight gain?

There are many medications that can be obesogenic or can cause weight gain. Following medications can potentially cause variable weight gain in some individuals.

• Some beta-blockers and calcium channel blockers
• Anti-diabetes medications such as insulins, sulfonylureas, thiazolidinediones, and meglitinides
• Hormone therapies such as glucocorticoids and injectable progestins
• Anti-seizure medications, including carbamazepine, gabapentin, valproate, and pregabalin
• A wide variety of different antidepressants
• Some mood stabilizers
• Migraine medications such as amitriptyline and paroxetine
• Some antipsychotics
• Chemotherapeutic and anti-inflammatory agents

How should weight loss medications be used in conjunction with other forms of treatment?

A treatment plan for obesity can comprise multiple forms of treatment, including medications, diet, exercise, and/or surgery. All weight loss medications work best in the context of a healthy eating plan and exercise. Even when a patient is engaging in exercise and other lifestyle adjustments, medications can help with hunger, cravings, and metabolic preservation.

How long do weight-loss medications need to be taken?

Some weight management medications are designed for short-term use and others for long-term use. For example, some are approved by the FDA 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 (Zepbound, Mounjaro).

The dosing for some of these includes a long ramp-up period—up to five months—to reach full dosage.

How have options in weight loss medications changed in recent years?

While GLP-1 RAs have grabbed a lot of headlines, they are only the latest in a long history of evolving weight loss medications. A 2022 article in Life Science explains:

“…as more physiological mechanisms for weight gain have been unearthed, drugs targeting newly discovered receptors and/or enzymes have been introduced with improved safety profiles and fewer psychological adverse events. Additionally, drugs targeting hunger or satiety signaling have been actively studied and have shown increased adoption by physicians. Studies have also evaluated drugs that target metabolic tissues—such as adipose tissue or muscle—to promote weight loss, however to-date nothing has carried on into clinical practice.”

Undoubtedly, new candidates will continue to be developed, and some will come to market.

How do they affect weight regain?

AOMs may counter the effects of metabolic adaptation and prevent weight regain. After weight reduction, the body metabolically adapts, often causing an increase in hunger hormones and a decrease in satiety hormones and resting metabolic rate, all of which can contribute to weight regain. If the patient achieves clinically meaningful weight reduction with anti-obesity medications and if the clinician and patient feel that the medication is helping to avoid weight regain, then a weight reduction plateau should not be considered a point where medication should be discontinued, but rather the medication should be continued for weight reduction maintenance.

What are the differences between OTC and prescription weight loss medications?

The only over-the-counter medicine for weight loss 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 to confirm their safety and effectiveness.

With prescription medications, a healthcare professional can weigh all factors affecting the patient’s lifestyle and BMI, and also monitor progress and side effects. This relationship can allow for dosage adjustments or alternative medications if one seems like a better fit for the patient.

What is the connection between antidepressant medication and weight loss?

Many antidepressants are weight-positive (cause weight gain), some are weight-neutral, and at least one is weight-negative (causes weight loss).

Antidepressants are broken down into categories: selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAO inhibitors), and others. Medications within each of these categories can cause weight gain.

In the SSRI group, Paroxetine shows the highest associated weight gain. Other SSRIs, including Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), and Sertraline (Zoloft), have variable effects on weight, and some do not show weight gain until after six months of use.

Les médicaments antidépresseurs tricycliques favorisant la prise de poids comprennent l’amitriptyline, la doxépine et l’imipramine. La désipramine, la nortriptyline et la protriptyline ont des effets variables sur le poids.

Le bupropion (Wellbutrin), une aminocétone, est considéré comme un anti-poids négatif et est prescrit à la fois pour favoriser la perte de poids et pour traiter la dépression. Cependant, chaque personne réagit différemment aux antidépresseurs.

Quels médicaments pour perdre du poids sont connus pour supprimer l’appétit ?

Les médicaments suivants, approuvés par la FDA, suppriment l’appétit : tirzépatide (Zepbound), liraglutide (Saxenda), naltrexone-bupropion (Contrave), phentermine-topiramate (Qysmia), ainsi que les stimulants suivants : benzphétamine (Didrex™), diéthylpropion (Tenuate™), phentermine (Adipex-P, ProFast) et phendimétrazine. Chaque médicament a un effet différent sur l’appétit.

Vous cherchez un traitement contre l’obésité ? Cliquez pour trouver un spécialiste de l’hôpital Erdem près de chez vous qui pourra vous aider à trouver les médicaments amaigrissants les mieux adaptés à vos besoins.

Citations

1. Dzay, Omar, et al. Recherches en ligne d’inhibiteurs du SGLT-2 et d’agonistes du récepteur du GLP-1 corrélées aux taux de prescription aux États-Unis : étude infodémiologique. Frontiers in Cardiovascular Medicine. 2022 ; 9 : 936651
2. NIH, Bibliothèque nationale de médecine, Medline Plus, Orlistat.
3. Food and Drug Administration (FDA) des États-Unis. La FDA approuve un nouveau traitement médicamenteux pour la gestion chronique du poids, une première depuis 2014. 4 juin 2021.
4. Park, Alice. De nouveaux médicaments pour perdre du poids arrivent, et ils pourraient être encore plus efficaces. Time, 26 juin 2023.
5. Cairns, Elizabeth. Amgen tente une nouvelle approche contre l’obésité . Évaluer Vantage, 5 décembre 2022.
6. Seaborg, Eric. L’approche hormonale pourrait-elle être la clé du traitement de l’obésité ? Endocrine News, octobre 2021.
7. Dagam Jeong, Ronny Priefer. Médicaments anti-obésité pour la perte de poids : utilisation à court et à long terme. Life Sciences, volume 306, 2022, 120825.
8. Ghusn, Wissam, MD, et al. Résultats de la perte de poids associée au traitement par sémaglutide chez les patients en surpoids ou obèses. JAMA Network Open. 2022 sept. ; 5(9) : e2231982.
9. Wilding, John PH, MD, et al. Sémaglutide une fois par semaine chez les adultes en surpoids ou obèses. The New England Journal of Medicine, 18 mars 2021.
10. Haelle, Tara. L’AGA publie des recommandations sur les médicaments anti-obésité pour la gestion du poids. Medscape, 21 octobre 2022.
11. Rasmussen, Louise et Michael Erman. Les pilules amaigrissantes Novo Nordisk et Pfizer sont aussi efficaces que les injections. Reuters, 22 mai 2023.
12. NIH, Institut national du diabète et des maladies digestives et rénales.
13. Neuman, Tricia et Juliette Cubanski, « Que pourraient signifier les nouveaux médicaments contre l’obésité pour Medicare ? » Kaiser Family Foundation, 18 mai 2023.