Man weighing himself and wondering what the most effective weight loss pill is

What Is the Most Effective Weight Loss Pill?

Written on October 13, 2023 by Sendra Yang, PharmD, MBA. To give you technically accurate, evidence-based information, content published on the Everlywell blog is reviewed by credentialed professionals with expertise in medical and bioscience fields.

Table of contents

Obesity is a chronic disease that impacts over 650 million adults globally.[1] In the United States, the obesity prevalence was measured at 42% from 2017 to March 2020.[2] In 2019, estimated medical costs due to obesity in the United States were approximately $173 billion annually.

Continue reading to learn more about obesity and the benefits of weight loss when you are overweight or obese. You will also be able to find out information on treatment options for obesity and what is the most effective weight loss pill.

More about Obesity

Health conditions related to obesity include heart disease, stroke, type 2 diabetes, and certain cancers that are among the leading causes of preventable and premature death.[2] Other serious health conditions that people with obesity are at an increased risk for include[2,3]:

  • High blood pressure or hypertension
  • High cholesterol, low HDL cholesterol, or increased triglycerides
  • Gallbladder disease
  • Osteoarthritis, which is a breakdown of cartilage and bones in joints
  • Sleep apnea
  • Depression and anxiety
  • Difficulty with physical functioning and body pain

Benefits of Weight Loss

Losing weight anywhere from 5% to 10% of total body weight can significantly improve health for those who are overweight or obese.[4] This modest amount of weight loss can help with managing type 2 diabetes and lead to more energy and better sleep. Weight loss benefits also include improvements in stress, gastroesophageal reflux disease (or GERD), polycystic ovary syndrome, and fatty liver disease.[5,6]

Research has found that weight loss of more than 10% has further major beneficial impacts on obesity-related complications, such as type 2 diabetes and hypertension.[5] Improved glucose metabolism and cardiovascular risk factors were reported in patients with significant weight loss.

Treatment Options for Obesity

Weight loss can be achieved through lifestyle modifications like diet and exercise.[7,8] However, diet and exercise are sometimes insufficient for weight loss. Losing weight may require medications or surgery.

Weight management and weight loss are central to treating overweight and obesity.[7,8] A comprehensive lifestyle intervention plan designed for losing weight is recommended for all overweight and obese patients looking to lose weight.[7] Lifestyle modifications may involve a healthy meal plan, increased physical activity, and behavioral interventions.

Several medications have been approved by the U.S. Food & Drug Administration (FDA) for chronic weight management.[7,9] Currently, five drugs are FDA-approved for long-term weight loss, including:

  • Orlistat (Xenical®)
  • Phentermine-topiramate (Qsymia®)
  • Naltrexone-bupropion (Contrave®)
  • Liraglutide (Saxenda®)
  • Semaglutide (Wegovy®)

A sixth drug, setmelanotide (Imcivree®), is approved only for people diagnosed with one of three rare genetic disorder.[7] Saxenda®, Wegovy®, and Imcivree® are all formulated as injections.

What Is the Most Effective Weight Loss Pill?

Answering the question of which FDA-approved weight loss pill is most effective isn't necessarily a straightforward exercise. Your healthcare provider can help determine the most effective weight loss pill for you based on your personal circumstances and preferences.

What is certain is that the surest way to get results is to take the weight loss pill as prescribed. Some side effects of a particular pill may deter individuals from wanting to use that drug for weight loss. Below, is an in-depth description of each of the pills that are FDA-approved for chronic weight loss.

Everlywell Weight Loss Support

Orlistat (Xenical®)

Orlistat belongs to the drug class called lipase inhibitors.[7,9,10] The drug is approved for weight management for obese or overweight adults who also have other risk factors. Orlistat is intended to be used in combination with a reduced caloric diet.[10] It can also be used to reduce the risk of weight regain after prior weight loss. It is taken by mouth as one 120 mg capsule three times a day with each main meal. Common side effects include oily discharge, flatus with discharge, fecal urgency, and fatty or oily stool.[10]

Orlistat works by deactivating intestinal enzymes and making them unable to break down dietary fats so they cannot be absorbed, resulting in a caloric deficit and positively impacting weight control.[10] In a one-year approval study, 55% of adult patients treated with the medication achieved at least a 5% weight loss from baseline compared to 27% of placebo-treated patients.[10] After two years, the same study showed that 45% of the orlistat-treated group (compared to 24% in the placebo group ) had achieved at least a 5% weight loss from baseline. The one-year results for achieving at least 10% weight loss from baseline was 25% in the orlistat group compared to 8% in the placebo group. The two-year results for this endpoint are comparable.

Phentermine-Topiramate (Qsymia®)

Phentermine-topiramate is a drug used in combination with diet and exercise for chronic weight management in obese and overweight adults.[7,9,11] The medication is taken daily in the morning, with or without food.[11] The starting dose is 3.75 mg of phentermine/23 mg of topiramate, and this dose is increased after 14 days. Further increase of dosage is based on an evaluation of how much weight the patient has lost. Qsymia® comes in an extended-release capsule with the two drugs. Common side effects are dry mouth, constipation, headache, insomnia, and dizziness.

The exact way phentermine-topiramate works is not entirely understood. Still, it is proposed to reduce appetite, decrease food consumption, and increase satiety by impacting the release of various transmitters in the brain.[11] In an initial study with obese patients, higher dosages of the medication showed greater weight loss. 19% of individuals who received a 3.75 mg/23 mg dose lost 10% or greater total body weight from baseline, compared to 47% of individuals who received a 15 mg/92 mg dose. Only 7% of participants in the placebo group lost a similar amount of weight. A second study with patients who were obese or overweight and had comorbidities reported similar rates of weight loss.

Naltrexone-Bupropion (Contrave®)

Naltrexone-bupropion is another combination drug approved for chronic weight management for obese and overweight adults in combination with diet and exercise.[7,9,12] The medication is taken by mouth in the morning and the evening.[12] The dosage is increased on a weekly basis until the fourth week of use; the total daily dose from the fourth week onward is two 8 mg/90 mg tablets taken twice daily. Naltrexone-bupropion's common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, and dry mouth.

The exact way naltrexone-bupropion works for weight loss is not fully understood.[12] It is theorized that the drug impacts two different food intake regulation areas in the brain that control appetite and the reward system. In one of the studies used for FDA approval (COR-1), 42% of adult patients treated with the medication achieved at least a 5% weight loss from baseline compared to 17% of placebo-treated patients.[12] The results of achieving at least 10% weight loss from baseline was 21% in the naltrexone-bupropion group compared to 7% in the placebo group.

Next Steps with Everlywell

If you are obese or overweight and interested in losing weight, it is essential to speak with a healthcare provider. At Everlywell, you can access our comprehensive Weight Care+ program. This telehealth program provides regular virtual meetings with a licensed clinician, access to prescriptions if you qualify, and lifestyle content and support for your health-related conditions.

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  1. Obesity and overweight. World Health Organization. Accessed October 9, 2023.
  2. Adult obesity facts. Centers for Disease Control and Prevention. May 17, 2022. Accessed October 9, 2023.
  3. Health effects of overweight and obesity. Centers for Disease Control and Prevention. September 24, 2022. Accessed October 9, 2023.
  4. Healthy weight. Centers for Disease Control and Prevention. December 30, 2022. Accessed October 9, 2023.
  5. Tahrani AA, Morton J. Benefits of weight loss of 10% or more in patients with overweight or obesity: A review. Obesity (Silver Spring). 2022;30(4):802-840. doi:10.1002/oby.23371.
  6. Fruh SM. Obesity: Risk factors, complications, and strategies for sustainable long-term weight management. J Am Assoc Nurse Pract. 2017;29(S1):S3-S14. doi:10.1002/2327-6924.12510.
  7. Cornier MA. A review of current guidelines for the treatment of obesity. Am J Manag Care. 2022;28(15 Suppl):S288-S296. doi:10.37765/ajmc.2022.89292.
  8. Wharton S, Lau DCW, Vallis M, et al. Obesity in adults: a clinical practice guideline. CMAJ. 2020;192(31):E875-E891. doi:10.1503/cmaj.191707.
  9. Prescription medications to treat overweight & obesity - NIDDK. National Institute of Diabetes and Digestive and Kidney Diseases. Accessed October 9, 2023.
  10. DailyMed - Xenical- Orlistat capsule. U.S. National Library of Medicine. Accessed October 9, 2023.
  11. DailyMed - QSYMIA- phentermine and topiramate capsule, extended release. U.S. National Library of Medicine. Accessed October 9, 2023.
  12. DailyMed - contrave extended-release- naltrexone hydrochloride and bupropion hydrochloride tablet, extended release. U.S. National Library of Medicine. Accessed October 9, 2023.
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