Clinical Approaches to the Management of Obesity
July 1, 2021
July 31, 2023
Lalita Prasad-Reddy, PharmD, MS, BCPS, BCACP, CDCES
Assistant Dean for Student Affairs, Associate Professor of
Chicago State University–College of Pharmacy
Clinical Pharmacy Specialist, Associate Director of Pharmacology,
Assistant Professor of Internal Medicine
Rush University Medical Center
Marina Ghazer, PharmD Candidate 2021
Chicago State University–College of Pharmacy
FACULTY DISCLOSURE STATEMENTS
Dr. Prasad-Reddy and Ms. Ghazer have no actual or potential conflicts of interest in relation to this activity.
Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.
Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge
This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.
Exam processing and other inquiries to:
CE Customer Service: (800) 825-4696 or firstname.lastname@example.org
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
To understand the impact of the obesity epidemic in the United States and identify methods for prevention, diagnosis, and management in patients who are overweight or obese.
After completing this activity, the participant should be able to:
- Describe the diagnosis and classification of obesity according to U.S. guidelines.
- Explain the multimodal approach to managing overweight and obesity in adults, including lifestyle modifications, pharmacologic therapy, and bariatric surgery.
- Discuss the characteristics of pharmacologic agents used to manage overweight and obesity.
- Outline counseling points for patients who present with overweight or obesity.
ABSTRACT: In the United States and worldwide, obesity is a major public-health concern. Obesity is associated with a higher risk of morbidity and mortality, and it significantly increases patients’ risk of developing cancer, cardiovascular disease, and diabetes; however, it remains underassessed and frequently undiagnosed. Health-promoting behaviors, lifestyle modifications, pharmacotherapy, and bariatric surgery are all potential treatment modalities that can be considered, as appropriate, for patients who are overweight or obese. Clinicians should consult current guidelines and routinely assess patients for the presence of obesity and associated diseases, and pharmacists should initiate counseling interventions when obesity is identified.
Obesity is a significant public-health crisis both in the United States and abroad. According to the CDC, this condition affects more than 40% of the U.S. population.1 Worldwide, nearly 2 billion persons are overweight and more than 650 million meet the criteria for obesity.2 Obesity was previously considered a disease of adulthood; however, recent evidence suggests that its prevalence is increasing in U.S. children and adolescents, with almost 20% of those aged 2 to 19 years considered obese—a circumstance that underscores the importance of initiating healthy dietary behaviors and physical activity in early childhood.3
Obesity is associated with a higher risk of morbidity and mortality and a lower life expectancy, and it significantly increases the risk of cancer, cardiovascular (CV) disease, and diabetes; it also greatly raises economic, societal, and healthcare costs.4-6 One study estimated the global economic toll of obesity at almost $2 trillion.7 In 2016, the American Association of Clinical Endocrinologists (AACE) suggested that obesity be thought of as adiposity-based chronic disease. This terminology was proposed to encourage clinicians to keep in mind the health-related consequences of obesity rather than focusing solely on BMI as a means of measurement.8
Definition and Evaluation of Obesity
Although definitions of obesity vary among professional organizations and societies, the most widely accepted definition is based on BMI. Patients with a BMI >25 kg/m2 are considered overweight, whereas those with a BMI >30 kg/m2 are considered obese. Obesity may be further subcategorized as class 1, BMI 30-35 kg/m2; class 2, 35-40 kg/m2; and class 3, >40 kg/ m2 (also called morbid obesity).9 These subclasses serve to identify patients at the extreme end of the obesity spectrum, who have the highest risk of developing obesity-related diseases.10
Obesity remains underassessed and frequently undiagnosed in a variety of clinical situations. A multitude of factors likely contribute to the absence of a uniform approach to diagnosis, including insufficient resources to appropriately support the needs of obese patients; clinician time constraints, which limit attention on preventive-care measures; provider lack of confidence in obesity identification and patient counseling; patient and provider concerns surrounding weight stigma; and an antifat bias among clinicians.11 All of these factors should be addressed and identified in outpatient and hospital settings to ensure that patients are appropriately assessed, diagnosed, and treated for obesity.
BMI is an inexpensive, easy-to-calculate screening method for identifying the presence of obesity, and it is also an indicator for health risks.12 Studies have demonstrated that BMI correlates with body-fat levels and that higher BMI is associated with a greater risk of obesity-related morbidity and mortality.13 Nonetheless, BMI is not without limitations. Clinicians should be cognizant that the extreme end of the BMI spectrum correlates with greater weight, not necessarily a higher percentage of body fat, and that it does not reflect distribution of body fat, degree of muscle mass, or bone contribution.14
In patients who present with an extremely high BMI, further investigation should include assessment of body fat. It is well known that the risk of obesity related diseases is primarily associated with a higher degree of adipose tissue; therefore, body-fat assessment should accompany BMI measurement, with clinical interventions focusing on reducing adipose tissue and improving body-fat distribution.15 However, this assessment is not routinely performed in practice owing to the cost, the impracticality of obtaining these measurements at bedside or in outpatient settings, and limited overall utility. One measurement that is easily obtained and should be assessed in all patients with an elevated BMI, according to the National Heart, Lung, and Blood Institute, is waist circumference. Studies suggest that increased waist circumference is highly indicative of future CV risk and directly increases metabolic risk factors such as hypertension, hyperlipidemia, and glucose.16 Interventions should be aimed at reducing waist circumference, as men and women whose waist circumference is >40 inches (102 cm) and 35 inches, respectively, are considered to be at increased risk for obesity-related diseases.17
All patients presenting with obesity should be screened for obesity-related diseases. Testing includes annual assessment of blood pressure (BP), lipid panels, and blood glucose, as well as screening and evaluation for CV disease, obstructive sleep apnea (OSA), and osteoarthritis.4 Because secondary causes of obesity can contribute to weight gain, other contributing factors and conditions that can precipitate obesity should be investigated. If possible, medications that can contribute to obesity should be avoided; agents such as corticosteroids, hormonal contraceptives, antidepressants, antipsychotics, and antihyperglycemics can all lead to to weight gain.5 Additionally, a number of diseases are associated with weight gain, so clinicians should be aware of and ensure appropriate management of commonly encountered conditions, such as hypothyroidism and depression, that can complicate obesity management.4-6
Obesity should be considered a disease, and appropriate intervention should be implemented in all patients to reduce body weight and prevent obesity-related diseases. Patients should be encouraged to adopt and maintain healthful lifestyle behaviors as a preventive strategy for reducing the risks of obesity and chronic diseases. Healthy-weight patients should have their weight, height, and BMI measured at each visit, and they should be counseled as necessary on approaches to mitigate weight gain and reduce CV risk factors.4-6 In patients who are overweight or obese at presentation, a more strenuous intervention is warranted.
The connection between excess body fat and obesity-related diseases is well established and provides a rationale for why aggressive therapy should be initiated in patients with elevated BMI or a higher body-fat percentage. A multimodal approach involving behavioral therapy, nutrition, physical activity, pharmaco therapy, and bariatric surgery may be considered. Although most guidelines suggest that weight loss of at least 10% is optimal for patients who are obese or overweight, clinicians must keep in mind that long term approaches to weight management are challenging and often unsustainable.18,19 Therefore, many clinicians consider a modest weight loss of 5% to 10% acceptable, as it has been associated with reductions in elevated CV biomarkers including BP, glucose, and cholesterol.4-6,17-19 Furthermore, patients who are extremely obese (BMI >40 kg/m2) may experience the most dramatic beneficial effects even with modest weight loss.20 Although improvements in CV risk factors occur with modest weight loss, increased weight loss is necessary for patients to achieve clinical improvements in conditions such as OSA or hepatitis or to significantly reduce the risk of obesity-related mortality.21
Several professional organizations have published clinical guidelines on the treatment of obesity. In 2013, the American Heart Association (AHA), the American College of Cardiology (ACC), and the Obesity Society (TOS) jointly published a clinical-practice guideline on obesity management.6 This was followed in 2016 by the Endocrine Society (ES) guideline focusing on pharmacologic management of obesity.5 Also in 2016, the AACE and the American College of Endocrinology published comprehensive guidelines with a treatment algorithm.4 Although the three guidelines have similarities, their approaches differ.
The AHA/ACC/TOS guideline recommends a systematic approach to the management of patients who are overweight or obese, whereas the AACE guidelines recommend a paradigm approach for disease prevention and management that includes routine assessment in all patients.4,6 As previously noted and as advocated by multiple guidelines, clinicians should assess patients for obesity and screen for obesity-related diseases at each visit. For patients with a normal BMI, evaluation of contributing lifestyle factors, medical history, and comprehensive lifestyle history is warranted. Patient education on healthful eating patterns, physical activity, and avoidance of weight gain is paramount. Secondary prevention strategies are employed in patients who are overweight or obese and have no preexisting obesity-related conditions. Interventions for this group are targeted to preventing weight gain, potentially achieving weight loss, and reducing risk of weight-related comorbidities. Patients with a BMI >25 and obesity-related disease—including prediabetes, diabetes, hypertension, hyperlipidemia, infertility, OSA, and myriad other diseases—are classified as needing tertiary prevention. Weight loss is recommended based on comorbid conditions, in a general range of 5% to 15% of current weight.4
Comprehensive lifestyle interventions are the foundational approach for weight loss, according to the AHA/ ACC/TOS guideline.6 Comprehensive lifestyle interventions encompass a number of strategies, including dietary modification, physical activity, and intensive behavioral management.6 The AACE guidelines, in contrast, advocate a tiered approach; as mentioned previously, primary and secondary prevention strategies center on weight-gain avoidance strategies or weight loss, whereas tertiary treatment prioritizes weight loss, for most patients ranging from 5% to 15% depending on the presence of comorbid conditions.4 The AACE guidelines note that the primary goal of any obesity care is the relief of obesity-related complications, rather than simple weight loss alone.4
While an exhaustive discussion of nonpharmacologic approaches to obesity is beyond the scope of this article, dietary modifications, physical activity, and risk factor avoidance are important and will be discussed here. According to the AACE guidelines, the primary focus of any weight-loss intervention should be targeted, caloric restriction. High-protein, high-fat, lowglycemic-load, low-carbohydrate, and Mediterranean diets all have data showing benefits for weight loss. Research demonstrates, however, that adherence to dietary behaviors is far more important than the individual macronutrient compositions of these diets.4
All individuals should embrace a lifestyle that limits sedentary behavior and promotes physical activity.
According to the Physical Activity Guidelines for Americans, adults should aim for 150 to 300 minutes of moderate physical activity per week (this can be decreased if intensity is vigorous).22 The AACE guidelines for weight loss mirror this recommendation.4 All weight-loss interventions should have a prescription for exercise, with a goal of achieving 150 minutes per week. Additional resistance training should be incorporated into activity regimens at least two to three times weekly.4
Weight-loss approaches are more successful when behavioral intervention is a focused component. Goal setting, self monitoring, education, problem solving, counseling, and stimulus control are all important aspects of a comprehensive weight-loss program.23 Multidisciplinary teams are essential for the success of weight-loss interventions, especially in the long term. Evidence supports frequent provider-patient contact as one of the best strategies for preventing weight gain in the long term.23
If lifestyle modifications are not successful in meeting weight-loss goals, pharmacologic treatment is an option. Once the decision has been made to initiate pharmacotherapy, the patient should be counseled regarding the importance of continued adherence to central health-promoting behaviors such as physical activity and behavioral therapy.4-6 Several agents are FDA approved for short-term (<12 weeks) and long-term weight-loss treatment. Short-term agents, such phentermine and diethylpropion, among others, will not be discussed here.19
Whereas the AACE guidelines recommend pharmacologic therapy only as an adjunct to diet and exercise, the ACC/AHA/TOS guideline advocates it for patients who have a BMI >27 kg/m2 and an obesity-associated comorbid condition (diabetes, hypertension, hyperlipidemia, or OSA) or for any patient with a BMI >30 kg/ m2.4,6 Although clinical trials have demonstrated the effectiveness of antiobesity agents versus placebo, adherence rates are often low, presumably because of adverse effects (AEs), nonadherence to health-promoting behaviors, or costs.19 It should be noted that if a patient does not experience clinically meaningful weight loss in the first 3 months of therapy, further continuation of the agent is not likely to be effective. The ES guideline recommends that if sufficient weight loss has not occurred after a period of 12 weeks, the agent should be discontinued and a different agent considered.5
Orlistat: Orlistat (as Xenical), which was introduced to the U.S. in 1999, was among the first weight-loss medications to be FDA approved as an adjunct to diet and exercise.19,24 It exerts its action by reversible inhibition of gastric and pancreatic lipases in the lumen of the gastrointestinal (GI) tract that ultimately decrease systemic absorption of dietary fat, and this subsequently results in a caloric deficit and a positive effect on weight control.19,24,25 This prescription agent is a 120-mg tablet dosed three times daily within 1 hour of a fatty meal.24 At the recommended dosage, Xenical inhibits dietary-fat absorption by approximately 30%.19 In 2007, an OTC lower-dose formulation (Alli) was approved by the FDA. Administered at a dosage of 60 mg three times daily, Alli blocks only 25% of dietary-fat absorption.19,26
The most commonly reported AE of orlistat is GI effects, including oily spotting, flatus with discharge, fatty and oily stool, increased defecation, and fecal incontinence.19,24-26 Ultimately, these AEs are extensions of the agent’s therapeutic ability to reduce fat absorption in the small intestine. Patients should be aware of the need to limit fat intake, as GI effects occur with a greater amount of fat.19 Because the AEs of orlistat are dose related, the OTC formulation appears to be better tolerated.27 Deficiencies of the lipid-soluble vitamins A, D, E, and K have been reported with the use of orlistat, as it inhibits fat absorption, thereby depleting the patient’s vitamin reserve.19 To avoid this effect, patients taking orlistat should be counseled to take a multivitamin daily, at least 2 hours before or after the orlistat dose.19,24,26
Orlistat’s efficacy was evaluated in a randomized, placebo-controlled trial that enrolled 391 overweight subjects.3 The use of orlistat 60 mg in mildly to moderately overweight subjects resulted in significant weight loss when used in addition to a hypocaloric diet. Compared with participants given placebo, those given orlistat achieved significantly greater weight loss from baseline to week 16, with a reduction of approximately 4.8 kg ± 0.35% versus 3.1 kg ± 0.38% for placebo (P <.001). Orlistat-treated subjects also realized improvements in CV biomarkers, including BP and lipids. It was concluded that orlistat, especially when used as an adjunct to lifestyle modifications, has efficacy and can contribute significantly to weight and risk-factor improvement in overweight patients.28
Phentermine/Topiramate Extended-Release: This combination product (Qsymia) is indicated for use as an adjunct to a hypocaloric diet and increased physical activity for weight management.5,19,29 Although phentermine has been employed for decades as a weight-loss agent, the use of topiramate for this purpose is a more recent development. The combination was approved in the U.S. in 2012 for long-term treatment of overweight and obesity in patients meeting BMI criteria.29,30
Phentermine is an anorectic and a sympathomimetic amine whose pharmacologic properties are similar to those of amphetamines. The effect of phentermine is mediated by the release of catecholamines in the hypothalamus, an action that results in reduced appetite and decreased food consumption. Topiramate’s effect may be due to its activity in both appetite suppression and satiety enhancement based on a combination of potential mechanisms.5,19,30 The recommended starting dosage of Qsymia is 3.75 mg/23 mg once daily for 14 days, after which the dosage is increased to 7.5 mg/46 mg once daily for 12 weeks.5,19 The dose should be escalated if the patient has not lost at least 3% of baseline body weight.19,30 If the patient has not lost at least 5% of baseline body weight after escalation therapy, use should be discontinued because it is unlikely that meaningful weight loss will be achieved with further use.19,30 Therapy should be titrated down, as abrupt discontinuation has led to seizure development in some patients.19,30
Although this combination product appears to be slightly more effective for weight loss compared with orlistat, AEs may limit its use.19,29,30 The most commonly reported AEs include constipation, paresthesias, and dry mouth, which patients often find intolerable. Serious AEs include metabolic acidosis, electrolyte changes, glaucoma, and cognitive impairments. Therefore, patients should be appropriately counseled on signs and symptoms of treatment in order to identify a potentially serious complication.19,29,30 Finally, Qsymia has a Risk Evaluation and Mitigation Strategies program based on its contraindication during pregnancy due to the increased risk of teratogenicity. Topiramate has been shown to potentially cause fetal growth restriction and oral cleft formation.30
The CONQUER trial evaluated the combination of phentermine and topiramate in 2,487 patients with a BMI of 27 kg/m2 to 45 kg/m2 who had two or more weight-related conditions.31 This 56-week randomized, double-blind trial compared two different phentermine/topiramate doses with placebo. Nonplacebo patients received either a goal dose of phentermine/ topiramate controlled-release (CR) 7.5 mg/46 mg or phentermine/topiramate CR 15 mg/92 mg after a titration period. All patients were counseled on the importance of lifestyle changes and caloric restriction. After the treatment period, both groups of patients given phentermine/topiramate exhibited significantly greater reductions in body weight versus placebo patients (–1.4 kg [least-squares mean (LSM), –1.2%; 95% CI, –1.8 to –0.7], LSM, –8.1 kg [–7.8%; –8.5 to –7.1; P <.0001], and LSM, –10.2 kg [–9.8%; –10.4 to –9.3; P <.0001] for placebo, lower-dose combination, and higher-dose combination, respectively). Additionally, a significantly greater percentage of patients in both combination-drug groups experienced weight loss of at least 5%.31
Lorcaserin: Lorcaserin (Belviq), which is no longer on the market, was FDA approved in 2012 for weight loss in obese patients and overweight patients with additional weight-related risk factors. The exact mechanism of action for lorcaserin is unknown, but the drug is thought to promote satiety and decrease food consumption by selective activation of 5-HT2C receptors on anorexigenic neurons in the hypothalamus.19
On January 14, 2019, the FDA announced that, based on a preliminary analysis of clinical-trial data, there was a possible increased risk of cancer with the use of lorcaserin. On February 13, 2020, the FDA requested that the manufacturer (Eisai Inc.) voluntarily withdraw Belviq and Belviq XR from the U.S. market based on this safety concern, and the manufacturer complied with this request. Providers were advised to immediately inform patients about the cancer risk, ask them to stop taking the medication, and discuss alternative weight-loss medications or strategies. The FDA does not advise special screening for patients who have previously taken lorcaserin; standard screening recommendations for cancer should be followed.32
Liraglutide: This agent entered the U.S. market (under the brand name Victoza) in 2010 as an adjunct to diet and exercise for improving glycemic control in adults with type 2 diabetes.5,33 At a dosage of 1.8 mg daily, liraglutide has demonstrated significant reductions in A1C, enhanced CV biomarker profiles, and a reduction in atherosclerotic CV disease events.33 In 2014, a higher-dose formulation of liraglutide was approved by the FDA under the brand name Saxenda.5,34 At a dosage of 3 mg daily—which is higher than the dosage used for type 2 diabetes—Saxenda is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults.5,34
Glucagon-like peptide-1 (GLP-1) is a native hormone that acts as a physiological regulator of appetite by slowing gastric emptying and increasing satiety after eating, thus promoting weight loss.35 Liraglutide is an acylated GLP-1 receptor agonist with 97% homology to endogenous GLP-1.33 Similarly to endogenous GLP1, liraglutide binds and activates the GLP-1 receptor, overcoming endogenous dipeptidyl peptidase IV degradation.33-35 Owing to the delay in absorption and its stability against metabolic degradation, liraglutide is suitable for once-daily administration. The starting dosage of Saxenda is 0.6 mg once daily for 1 week, after which the dosage is increased by 0.6 mg weekly to a maximum of 3 mg once daily.5,34,35
The most common AEs experienced while taking liraglutide are GI symptoms such as nausea, diarrhea or constipation, and vomiting.5,33-35 Pancreatitis also is a concern with all incretin mimetic therapies, including liraglutide.5 Unfortunately, up to 10% of patients discontinue treatment because of GI intolerability.35 To decrease the frequency of symptoms, slow titration is recommended.5,33-35
In the 2015 SCALE trial, investigators sought to determine whether use of liraglutide 3.0 mg daily was associated with clinically significant weight loss. This randomized, double-blind trial included 3,731 patients who did not have type 2 diabetes but met BMI criteria.3 Participants were assigned in a 2:1 ratio to receive either once-daily injections of liraglutide 3.0 mg (n = 2,487) or placebo (n = 1,244). At week 56, liraglutide patients had significantly greater weight loss (P <.001) compared with those who received placebo (the liraglutide group lost a mean of 8.4 ± 7.3 kg, and the placebo group lost a mean of 2.8 ± 6.5 kg [–5.6; 95% CI, –6.0 to –.51]). Additionally, a greater percentage of patients treated with liraglutide met weight-loss goals of 5% and 10% of body weight compared with placebo patients. As expected, the most common AEs were mild or moderate nausea and diarrhea. After 1 year of therapy, liraglutide 3.0 mg resulted in weight loss of 15% or more in about 14% of patients compared with 3.5% for placebo patients. It was concluded that liraglutide 3.0 mg as an adjunct to diet and exercise was associated with significant, sustained weight loss.36
Naltrexone/Bupropion: In 2014, the FDA approved this combination product (Contrave) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management.37 Naltrexone is an opioid antagonist, and bupropion is an antidepressant. The precise neurochemical effects leading to weight loss are not fully understood, but it is hypothesized that naltrexone and bupropion act on two separate areas of the brain that are involved in food intake (the hypothalamus and the mesolimbic dopamine circuit).38 The optimal dosage of Contrave is naltrexone/bupropion 32 mg/360 mg, which is reached after an initial titration period of 4 weeks.5,38 Although the most commonly reported AE is headache, the combination is also associated with GI intolerances (nausea, constipation, diarrhea, vomiting) and central nervous system AEs including insomnia and dizziness.5,38 Contrave is associated with a resting increase in heart rate and BP; therefore, it is contraindicated in patients with uncontrolled hypertension. Because the combination product contains bupropion, it carries the same black box warnings as bupropion for neuropsychiatric reactions and suicidality, and it is contraindicated in patients with a history of seizure disorder, anorexia nervosa, or bulimia.5,37,38
The efficacy and safety of the naltrexone/bupropion combination was investigated in a series of four clinical trials (the COR trials) in obese patients who had an uncontrolled obesity-related disease, with the fourth COR trial evaluating its use in patients with diabetes. In all of these trials, which enrolled more than 4,500 patients, this drug combination was associated with greater weight loss compared with placebo when used as an adjunct to diet and exercise. Patients in the diabetes trial who received this drug combination in the diabetes trial also exhibited improvements in A1C, BP, and lipids.38,39
Optimal management of obesity involves a multimodal approach including health-promoting behaviors, behavioral interventions, and (if indicated) pharmacologic therapy or bariatric surgery. Obesity remains a major public-health concern, and pharmacists are in a unique position to counsel patients on lifestyle modifications, provide behavioral intervention and followup, and monitor for efficacy and toxicity of pharmacologic agents. As the most accessible healthcare professionals, pharmacists are in a pivotal role to address the obesity epidemic and contribute to a healthier, more sustainable society.
1. CDC. Adult obesity facts. www.cdc.gov/obesity/data/adult.html. Accessed December 15, 2020.
2. Ruban A, Stoenchev K, Ashrafian H, Teare J. Current treatments for obesity. Clin Med (Lond). 2019;19(3):205-212.
3. CDC. Childhood obesity facts. www.cdc.gov/obesity/data/childhood. html. Accessed December 20, 2020.
4. Garvey WT, Mechanick JI, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22(7):842-884.
5. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362.
6. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129(25 suppl 2):S102-S138.
7. Dobbs R, Sawers C, Thompson F, et al. Overcoming Obesity: An Initial Economic Analysis. Jakarta, Indonesia: McKinsey Global Institute; 2014.
8. Frühbeck G, Busetto L, Dicker D, et al. The ABCD of obesity: an EASO position statement on a diagnostic term with clinical and scientific implications. Obes Facts. 2019;12(2):131-136.
9. CDC. Defining adult overweight & obesity. www.cdc.gov/obesity/ adult/defining.html. Accessed January 15, 2021.
10. Freedman DS, Khan LK, Serdula MK, et al. Trends and correlates of class 3 obesity in the United States from 1990 through 2000. JAMA. 2002;288(14):1758-1761.
11. Ma J, Xiao L, Stafford RS. Underdiagnosis of obesity in adults in US outpatient settings. Arch Intern Med. 2009;169(3):313-314.
12. Ryan DH, Kahan S. Guideline recommendations for obesity management. Med Clin North Am. 2018;102(1):49-63.
13. Pi-Sunyer X. The medical risks of obesity. Postgrad Med. 2009;121(6):21-33.
14. CDC. Body mass index: considerations for practitioners. www. cdc.gov/obesity/downloads/bmiforpactitioners.pdf. Accessed February 1, 2021.
15. Cornier MA, Després JP, Davis N, et al. Assessing adiposity: a scientific statement from the American Heart Association. Circulation. 2011;124(18):1996-2019.
16. Darsini D, Hamidah H, Notobroto HB, Cahyono EA. Health risks associated with high waist circumference: a systematic review. J Public Health Res. 2020;9(2):1811.
17. Klein S, Allison DB, Heymsfield SB, et al. Waist circumference and cardiometabolic risk: a consensus statement from Shaping America’s Health: Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30(6):1647-1652.
18. The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, MD: National Heart, Lung, and Blood Institute; 2000. NIH Publication No. 00-4084.
19. McKinney L, Skolnik N, Chrusch A. Diagnosis and Management of Obesity. Leawood, KS: American Academy of Family Physicians; 2013.
20. Pasanisi F, Contaldo F, de Simone G, Mancini M. Benefits of sustained moderate weight loss in obesity. Nutr Metab Cardiovasc Dis. 2001;11(6):401-406.
21. Ryan DH, Yockey SR. Weight loss and improvement in comorbidity: differences at 5%, 10%, 15%, and over. Curr Obes Rep. 2017;6(2):187194.
22. Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA. 2018;320(19):2020-2028.
23. Butryn ML, Webb V, Wadden TA. Behavioral treatment of obesity. Psychiatr Clin North Am. 2011;34(4):841-859.
24. Xenical (orlistat) package insert. South San Francisco, CA: Genentech, Inc; October 2013.
25. Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000;20(3):270-279.
26. Alli (orlistat) package insert. Moon Township, PA: GlaxoSmithKline; 2007.
27. Filippatos TD, Derdemezis CS, Gazi IF, et al. Orlistat-associated adverse effects and drug interactions: a critical review. Drug Saf. 2008;31(1):53-65.
28. Anderson JW, Schwartz SM, Hauptman J, et al. Low-dose orlistat effects on body weight of mildly to moderately overweight individuals: a 16 week, double-blind, placebo-controlled trial. Ann Pharmacother. 2006;40(10):1717-1723.
29. Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc; July 2012.
30. Lonneman DJ Jr, Rey JA, McKee BD. Phentermine/topiramate extended-release capsules (Qsymia) for weight loss. P T. 2013;38(8):446452.
31. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341-1352.
32. FDA. FDA requests the withdrawal of the weight-loss drug Belviq, Belviq XR (lorcaserin) from the market. www.fda.gov/drugs/ drug-safety-and-availability/fda-requests-withdrawal-weight-lossdrug-belviq-belviq-xr-lorcaserin-market?utm_campaign=FDA%20 requests%20the%20withdrawal%20of%20the%20weight-loss%20 drug%20Belviq%2C%20Belviq%20XR%20%28lorcaserin%29&utm_ medium=email&utm_source=Eloqua. Accessed November 5, 2020.
33. Victoza (liraglutide) package insert. Plainsboro, NJ: Novo Nordisk Inc; November 2020.
34. Saxenda (liraglutide) package insert. Plainsboro, NJ: Novo Nordisk Inc; December 2014.
35. Whitten JS. Liraglutide (Saxenda) for weight loss. Am Fam Physician. 2016;94(2):161-166.
36. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373(1):11-22.
37. Contrave (naltrexone HCl and bupropion HCl) package insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc; September 2014.
38. Sherman MM, Ungureanu S, Rey JA. Naltrexone/bupropion ER (Contrave): newly approved treatment option for chronic weight management in obese adults. P T. 2016;41(3):164-172.
39. Hollander P, Gupta AK, Plodkowski R, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36(12):40224029.