What are the most effective weight loss supplements?

The media has been captivated by the meteoric rise in interest surrounding Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists), whose brand names include Wegovy and Ozempic. A study published in Frontiers in Cardiovascular Medicine in 2022 found that there is a concurrent increase in both online searches and prescriptions for GLP-1 receptor agonists.

In light of the increased availability of weight loss medications, patients may inquire about the most potent or efficacious prescription medication for weight loss. The response is multifaceted. Determining the appropriate medication for an individual can be a challenging task at times. Additionally, the market is undergoing rapid change; therefore, it is essential to remain current on the pros and cons of the available alternatives.

Prescription Criteria for Weight Loss Medication

By calculating a person’s BMI, suitability for weight loss medications can be determined. The prescription process for the majority of medications begins at a body mass index (BMI) of 30 or higher, or 27 or higher for individuals with weight-related medical conditions.

Zepbound was granted approval for adults with a BMI of 30 or higher in November 2023. The doctor and patient should discuss the patient’s current health concerns, other medications, and family medical history for each individual case. Cost and adverse effects of the medication will also factor into the decision.

Although the FDA has granted approval exclusively to adults for certain weight loss medications, orlistat, semaglutide, and liraglutide are all approved for minors 12 years of age and older. During pregnancy, each of the medications listed here is contraindicated.

Medications Currently Available for Weight Loss

Numerous weight loss medications enter the market on a regular basis, while others have been available for several decades. The following are frequently prescribed weight control medications:

Ozempic, Semaglutide (Wegovy)

Wegovy is the brand name for the GLP-1 receptor agonist semaglutide. It received FDA approval in 2021. Approved for injection administration in adults and children 12 years and older who are obese (body mass index [BMI] not less than 30 for adults, or 95th percentile for age and gender for children) or certain adults who are overweight (BMI] not less than 27) and have weight-related medical conditions. For the 2.4 mg dosage, the dosage must be increased progressively over the course of 16 to 20 weeks. This progression has the potential to mitigate adverse effects such as fatigue, headache, and vertigo, in addition to gastrointestinal symptoms.

Similar to Ozempic, but approved for the treatment of type 2 diabetes.

Mounjaro, Tirzepatide (Zepbound)

As Mounjaro, tirzepatide was previously approved for the treatment of type 2 diabetes. Zepbound is an approved treatment for obesity in adults with a body mass index (BMI) of 30 or higher.

It functions as a GLP-1 and GIP receptor agonist and, similar to semaglutide, suppresses appetite; it is intended to be utilized in conjunction with physical activity and diet for weight loss. Additionally, it is administered via injection.

Liraglutide, also known as Saxenda

Liraglutide is a once-daily injectable medication that inhibits appetite signals and increases the patient’s sense of fullness by modulating gut hormones that transmit signals to the brain. Daily dosing ranges from 0.6 mg to 3 mg. Certain patients may experience a 5–10% reduction in body weight, particularly when prescribed the higher dose of liraglutide.

Nausea, diarrhea, constipation, vomiting, renal insufficiency, headache, decreased appetite, dyspepsia, exhaustion, dizziness, abdominal pain, and increased lipase are among the adverse effects. Patients with a personal or familial history of medullary thyroid carcinoma or type 2 multiple endocrine neoplasm syndrome should not receive this treatment.

Phentermine (Suprenza, Adipex)

Phentermine is the most extensively used and oldest weight loss medication. It was initially prescribed as a transient remedy to stimulate weight loss; however, more recent medical protocols have incorporated it into long-term treatment regimens. Phentermine may induce a 5% reduction in body weight in some patients.

Phentermine is virtually exclusively offered in the HCl formulation in the United States, with strengths of 15 mg and 30 mg. Headache, overstimulation, hypertension, insomnia, tachycardia, and tremor are among the adverse effects.

Potential drug interactions may arise during or within fourteen days after the administration of certain anesthetic agents, sympathomimetics, alcohol, adrenergic neuron-blocking medications, or monoamine oxidase (MAO) inhibitors.

Topiramate-phentermine (Qsymia)

Phentermine and topiramate may be combined for the purpose of suppressing appetite and cravings. The combination of two medications enhances their efficacy.

Adults who are obese and suffer from migraines are suitable candidates for this weight loss medication. On average, certain patients may experience a 5–10% reduction in body weight.

The weight loss supplement should be progressively discontinued after 12 weeks if no further than 5% weight loss is observed despite taking the maximum dose.

The four concentrations of daily doses range from 3.75 mg/23 mg to 15 mg/92 mg. Abnormal sensations, vertigo, altered taste, insomnia, constipation, and parched mouth are among the adverse effects. Uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants are all contraindications.

Contrave (naltrexone-bupropion)

Naltrexone-bupropion is an antidepressant and opioid receptor antagonist combined to inhibit appetite and cravings by targeting the pleasure-reward regions of the brain. A few patients might experience a 5–10% reduction in body weight.

Commence treatment with one 8/90 mg tablet per day and increase progressively to four tablets. Nausea, constipation, headache, vomiting, vertigo, insomnia, dry mouth, and diarrhea are the most frequent adverse effects. Patients who are on narcotics for chronic pain or who have a seizure disorder should not be prescribed this medication.

 Imcivree (Setmelanotide)

 A melanocortin-4 receptor agonist, is prescribed for the purpose of managing weight chronically in pediatric and adult patients aged 6 years and older who are obese as a result of one of a number of distinct uncommon genetic disorders.

In order to establish the presence of the condition, genetic testing must identify variants in the LEPR, PCSK1, or POMC genes that are interpreted as pathogenic, likely pathogenic, or variant of uncertain significance (VUS).

Orlistat (Xenical and Alli)

Orlistat is a capsule-based lipase inhibitor that functions by impeding the enzymatic process responsible for the breakdown of dietary lipids. It impedes the absorption of dietary lipids in this manner.

After that, undigested fat is eliminated from the body. It is recommended for utilization in conjunction with a low-calorie diet and is also intended to decrease the likelihood of weight regain.

A few patients might experience a 5% reduction in body mass. One 120 mg capsule should be taken three times daily with each primary meal that contains fat, either during or for up to one hour after the meal.

A formulation available over-the-counter consists of 60 mg capsules to be taken with each meal that contains fat. Fecal incontinence, increased defecation, oily discharge from the rectum, and flatus with discharge are the most frequent adverse effects of orlistat.

Hydrogel (Plenity)

A 2019 saw the FDA approval of Plenity, a medical device rather than a medication, for individuals with a BMI between 24 and 40. Media coverage of the treatment has escalated in tandem with the emergence of GLP-1 receptor agonists.

It is composed of a capsule through which a superabsorbent, biodegradable hydrogel is secreted into the stomach. Satiety is increased by the substance, allowing the individual to consume less food. Real-world investigations have found that the mean weight loss is 9%.

For a more comprehensive analysis of the aforementioned weight loss medications, consult the most recent iteration of the Obesity Algorithm® published by the Obesity Medicine Association.

Weight Loss Medications to Come

Increasing obesity rates and fervent consumer demand for weight loss medications will inevitably lead to the introduction of additional medications in the coming years.

Lilly is developing the oral GLP-1 inhibitor orforglipron. Another injectable, retatrutide, specifically targets glucagon, GLP-1, and GIP. Additionally, Pfizer is developing two GLP-1 inhibitors for oral administration. Amgen, meanwhile, is conducting clinical trials of a drug candidate that functions as both a GLP-1 receptor agonist and a GIP receptor antagonist, in contrast to semaglutide, which is a dual agonist.

Scholars persist in their pursuit of hormones that influence appetite, including peptide YY, as potential pharmaceutical targets for obesity.

In a 2021 interview with Endocrine News, Robert Kushner, MD, a professor at the Feinberg School of Medicine of Northwestern University, praised “the new direction that we are taking in obesity treatment, treating it more as an endocrine disease, treating it hormonally…,” which provides patients and providers with a variety of options from which to select the most effective medication.

Another “hot” area in drug development for a variety of diseases, including obesity, are monoclonal antibodies. An infusion formulation of the monoclonal antibody bimagrumab, which targets to augment muscle mass and reduce adiposity, is presently under investigation.

As more options become accessible, physicians will have an enhanced capacity to tailor treatments by matching patients with the most effective medications. Obtain further insights into these novel alternatives by enrolling in OMA’s course titled “Future Developments in Anti-Obesity Medications.”

Frequent Questions Regarding Medication for Weight Loss

What is the efficacy of weight loss medications?

FDA-approved anti-obesity medications (AOMs) are evidence-based, safe therapies that ameliorate the disease by targeting specific physiologies. They are most efficacious when utilized in conjunction with a comprehensive treatment regimen. A person’s weight loss is influenced by a variety of factors, including the medications they take, their general health, and other personal considerations.

Despite the proliferation of weight loss medications, certain drugs have been withdrawn due to safety concerns and inadequate efficacy.

What is the most potent prescription medication for weight loss?

The magnitude of weight loss that can be achieved with semaglutide is substantial, according to clinical studies. A 2022 study involving 175 participants revealed a weight loss of 5.9% after three months and 10.9% after six months. A more extensive investigation, which was published in the New England Journal of Medicine, revealed an average loss of 14.9%. Semaglutide’s disadvantages, however, consist of an exorbitant price tag, adverse effects, and a prolonged to indefinite course of treatment.

Similar to other obesity treatments, an individual may observe superior outcomes with a particular medication. Each individual, in consultation with their physician, should seek the optimal combination of treatments that produces the most favorable results.

The American Gastroenterological Association issued weight loss medication recommendations in 2022 for obese patients who fail to demonstrate sufficient response to lifestyle modifications alone. Four options for the first line were enumerated:

•  Semaglutide
• Liraglutide
• Extended-release
• phentermine-topiramate (ER) supplements
• Narcotic-bupropion extended release (ER) formulation

In addition, phentermine and diethylpropion were suggested. It should be noted that these recommendations were put forth prior to Zepbound’s approval.

How do medications for weight loss function?

They function predominantly through the regulation of hormones in the adipose tissue, digestive tract, and brain in order to inhibit appetite and cravings and promote satiety.

While certain drugs are applied topically, others are administered subcutaneously via injection. Patients who inquire about the comparison between weight loss tablets and injections typically bring up the two alternatives pertaining to GLP-1 RAs. According to data independently published by Novo Nordisk and Pfizer in May 2023, the efficacy of tablets and injections is comparable.

Do any medications have the potential to induce weight gain?

A wide array of medications have the potential to induce weight gain or act as obesogens. Some individuals may experience variable weight gain as a result of medication adherence.

A number of calcium channel blockers and beta-blockers
Medications used to treat diabetes, including insulin, sulfonylureas, thiazolidinediones, and meglitinides
Injectable progestins and glucocorticoids are examples of hormone therapies.
Medications used to treat seizures, such as pregabalin, carbamazepine, gabapentin, and valproate
An extensive assortment of distinct antidepressants
Certain mood-stabilizers
Migraine medications, including paroxetine and amitriptyline,
Certain antipsychotics
Agents of chemotherapy and anti-inflammatory activity

How ought weight loss medications to be administered in tandem with alternative treatment modalities?

An obesity treatment strategy may encompass a variety of interventions, such as surgical intervention, dietary modifications, physical activity, and medication. Every weight loss medication is most effective when combined with a healthy diet and regular exercise. Medication can assist with hunger, cravings, and metabolic preservation even when the patient is participating in physical activity and making other alterations to their lifestyle.

For what duration must weight loss medications be administered?

Certain medications for weight management are intended for short-term use, while others are intended for long-term use. Some, for instance, have received FDA approval for a maximum of 12 weeks.

Orlistat (Xenical, Alli), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy, Ozempic), and tirzepatide are among those approved by the FDA for long-term use.

Certain of these medications have a lengthy ramp-up period of up to five months before the maximum dose is reached. It is important to bear in mind that obesity is classified as a disease, and no medication can “cure” it permanently.

In what ways have weight loss medication options evolved over the past few years?

Despite the attention that GLP-1 RAs have received, they are merely the most recent in a lengthy line of weight loss medications that have evolved. A Life Science article from 2022 explains:

“…as additional physiological mechanisms underlying weight gain have been elucidated, pharmaceuticals that target recently identified enzymes and receptors have been developed, featuring enhanced safety profiles and reduced occurrences of psychological adverse events.”

 Furthermore, pharmaceuticals that modulate appetite or satiety signals have been the subject of intensive research and have gained greater acceptance among physicians. Drugs that target metabolic tissues, including muscle and adipose tissue, have also been the subject of research to facilitate weight loss. However, as of now, none of these substances have been implemented in clinical practice.

Some new candidates will undoubtedly continue to be developed and introduced to the market.

In terms of cost, how do the various categories of weight loss medications compare?

Like any medication, certain weight loss supplements have been available for an extended period of time, offer generic equivalents, and are generally more cost-effective. Anti-GLP-1 RAs are notoriously expensive. According to the Kaiser Family Foundation, the projected yearly net cost of Wegovy is $13,600. GoodRx indicates that phentermine is available for as little as $10.

The variability of insurance coverage will influence the decisions of many patients regarding the use of weight loss medications. Medicare does not fund medications for weight loss.

What is their impact on weight regain?

By inhibiting the effects of metabolic adaptation, AOMs might be able to avert weight regain. The body undergoes metabolic adaptations following weight loss, which frequently result in elevated levels of appetite hormones and decreased levels of satiety hormones and resting metabolic rate. These changes have the potential to contribute to weight regain. In the event that an anti-obesity medication leads to a weight reduction that is clinically significant and both the clinician and patient perceive the medication as effective in preventing weight regain, a weight reduction plateau should not be interpreted as an indication that the medication should be discontinued; instead, weight reduction maintenance treatment should be initiated.

What are the distinctions between over-the-counter and prescription medications for weight loss?

At this time, the sole over-the-counter weight loss medication that has received FDA approval is Alli (orlistat). Additional over-the-counter substances are classified as supplements. They are not subject to FDA regulation and lack adequate scientific evidence to support their safety and efficacy.

By monitoring progress and adverse effects, a healthcare professional can assess all lifestyle and BMI-influencing factors in conjunction with prescription medications. This association may facilitate modifications in dosage or the selection of alternative medications should the patient perceive them to be more suitable.

What is the relationship between weight loss and antidepressant medication?

At least one antidepressant induces weight reduction; others are weight-neutral; and the majority of antidepressants induce weight gain.

Certain types of antidepressants are classified as monoamine oxidase inhibitors (MAO inhibitors), selective serotonin reuptake inhibitors (SSRIs), or serotonin and norepinephrine reuptake inhibitors (SNRIs). Each of the medications in this classification is capable of inducing weight gain.

Among the SSRIs, Paroxetine is most strongly associated with weight gain. The weight-related effects of additional SSRIs, such as Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), and Sertraline (Zoloft), are inconsistent, with certain individuals failing to exhibit weight gain until six months into their treatment.

Amitriptyline, Doxepin, and Imipramine are tricyclic antidepressants that have been associated with weight gain. The effects of despramine, nortriptyline, and protriptyline on weight are variable.

Bupropion (Wellbutrin), an aminoketone, is prescribed for the dual purpose of promoting weight loss and treating depression, despite its weight-negative nature. However, antidepressant responses vary among individuals.

Which appetite-suppressing medications are associated with weight loss?

Tirzepatide (Zepbound), Liraglutide (Saxenda), Naltrexone-Bupropion (Contrave), Phentermine-Topiramate (Qysmia), and benzphetamine (Didrex™), diethylpropion (Tenuate™), phentermine (Adipex-P), ProFast), and phendimetrazine are stimulants that inhibit appetite. Each medication has a unique effect on appetite.