Food and Drug Administration's Obesity Drug Guidance Document

Colman, Eric

doi:10.1161/circulationaha.111.028381

Cited by 82 publications

(51 citation statements)

References 37 publications

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“…15 The 2004 update to this document maintained similar principles but increased the size of the required clinical trial to 3000 patients receiving active drug and 1500 receiving placebo. 15 These trials, which included generally young patients, had low rates of cardiovascular events and therefore could not assess cardiovascular benefit or harm with any confidence.…”

Section: Standard Of Safety: Regulatory and Clinicalmentioning

confidence: 97%

“…14 The European Medicines Agency approved the drug, but FDA regulators did not. 15 Rimonabant for Prevention of Cardiovascular Events (CRESCENDO), a long-term cardiovascular outcomes trial, was terminated after revealing an increased rate of serious psychiatric side effects including suicide at mean follow-up of 14 months. 16 Sibutramine, a selective serotonin and norepinephrine reuptake inhibitor, combined 2 previously effective but potentially dangerous mechanisms.…”

Section: The Checkered History Of Obesity Pharmacotherapymentioning

confidence: 99%

“…18 Others felt that patients with subclinical cardiovascular disease would be difficult to identify. 15 Ultimately, sibutramine was voluntarily removed from the market in 2010. 15 …”

Section: The Checkered History Of Obesity Pharmacotherapymentioning

confidence: 99%

“…The first FDA guidance document for obesity drugs, published in 1996, required a 1-year placebocontrolled trial of 1500 subjects, with a subset continuing for a second year of open-label drug exposure. 15 One member of the FDA's advisory panel proposed requiring trials powered for mortality or cardiovascular risk-factor outcomes, but such trials were considered impractical at that time. 15 The 2004 update to this document maintained similar principles but increased the size of the required clinical trial to 3000 patients receiving active drug and 1500 receiving placebo.…”

Section: Standard Of Safety: Regulatory and Clinicalmentioning

confidence: 99%

“…15 One member of the FDA's advisory panel proposed requiring trials powered for mortality or cardiovascular risk-factor outcomes, but such trials were considered impractical at that time. 15 The 2004 update to this document maintained similar principles but increased the size of the required clinical trial to 3000 patients receiving active drug and 1500 receiving placebo. 15 These trials, which included generally young patients, had low rates of cardiovascular events and therefore could not assess cardiovascular benefit or harm with any confidence.…”

Section: Standard Of Safety: Regulatory and Clinicalmentioning

confidence: 99%

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Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit

Cunningham

Wiviott

2014

Clinical Cardiology

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Obesity is a major correlate of cardiovascular disease. Weight loss improves cardiovascular risk factors and has the potential to improve outcomes. Two drugs, phentermine plus topiramate and lorcaserin, have recently been approved by the US Food and Drug Administration for the indication of obesity; a third, bupropion plus naltrexone, is under consideration for approval. In clinical trials, these drugs cause weight loss and improve glucose tolerance, lipid profile, and, with the exception of bupropion plus naltrexone, blood pressure. However, their effect on cardiovascular outcomes is unknown. In defining appropriate roles for these drugs in preventive cardiology, it is important to remember the checkered history of drugs for obesity. New weight-loss drugs share the serotonergic and sympathomimetic mechanisms that proved harmful in the cases of Fen-Phen and sibutramine, respectively, albeit with significant differences. Given these risks, randomized cardiovascular outcomes trials are needed to establish the safety, and potential benefit, of these drugs. This review will discuss the history of pharmacotherapy for obesity, existing efficacy and safety data for the novel weight-loss drugs, and issues in the design of postapproval clinical trials. IntroductionAdvances in prevention-smoking-cessation campaigns, statin therapy, and tight blood pressure (BP) control, among others-have contributed to decreases in the burden of coronary artery disease over the past several decades. However, the increasing prevalence of obesity and obesityassociated diseases like type 2 diabetes mellitus (T2DM) have tempered these gains. 1 Despite recent data suggesting a plateau, rates of obesity remain substantially higher than a few decades ago. 2 Intensive lifestyle interventions have produced clinically relevant weight loss, 3 but modest interventions that are feasible in the primary-care setting are less successful. 4 Many efforts to develop an effective and safe weight-loss pill have failed. In fact, the history of obesity pharmacotherapy has been notable for cardiovascular side effects, not benefits. In 2012, the US Food and Drug Administration (FDA) approved 2 medications for weight loss, the selective 5-HT 2C agonist lorcaserin and the combination pill phentermine plus topiramate; a third, bupropion plus naltrexone, is under consideration for approval at the time of this writing. 5 The mechanisms of

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Section: Standard Of Safety: Regulatory and Clinicalmentioning

confidence: 97%

Section: The Checkered History Of Obesity Pharmacotherapymentioning

confidence: 99%

“…18 Others felt that patients with subclinical cardiovascular disease would be difficult to identify. 15 Ultimately, sibutramine was voluntarily removed from the market in 2010. 15 …”

Section: The Checkered History Of Obesity Pharmacotherapymentioning

confidence: 99%

Section: Standard Of Safety: Regulatory and Clinicalmentioning

confidence: 99%

Section: Standard Of Safety: Regulatory and Clinicalmentioning

confidence: 99%

See 3 more Smart Citations

Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit

Cunningham

Wiviott

2014

Clinical Cardiology

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Should Pharmaceuticals Be Used as Weight Loss Interventions for Adolescents Classified as Obese by BMI?

2023

AMA Journal of Ethics

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Ethically evaluating prescription of weight loss pharmaceuticals for adolescents classified by body mass index (BMI) as obese requires reconsideration of how medicine's overreliance on BMI as a diagnostic criterion supports a weight normative approach to health. This commentary on a case suggests that weight loss is not a safe, effective, or permanent method of health promotion. The unknown extent of pharmacotherapeutics' risks to adolescents in addition to the controvertible benefits of weight loss ethically preclude their prescription, despite scientific consensus to fight obesity by prescribing weight reduction.Case M is a student at Sunnyvale High School. At 16 years old, they are currently enrolled in an intensive health behavior and lifestyle treatment (IHBLT) at the local county hospital. During the pandemic, their body mass index (BMI) increased from 28 to 30, making them a candidate for liraglutide, a glucagon-like peptide 1 (GLP-1) analogue approved by the US Food and Drug Administration (FDA) in 2020 as a weight loss medication in adolescents. As M's primary care physician, Dr B recommends liraglutide as an additional means for preventing M's becoming an obese adult with comorbidities. CommentaryResponding to the title question requires not only evaluating the risks and benefits of pharmacotherapy (particularly in adolescents), but also closely examining weight loss as a health goal. Present clinical practice is "weight normative" 1 in emphasizing weight and weight loss to define health and well-being. There is no more obvious manifestation of this practice than the continued use of BMI to define health status. BMI is based on the ratio of weight in kilograms to height in meters squared and is currently used as the identifying obesity indicator, 2,3 although its value does not reflect significant considerations of the obesity disease state, including peripheral and visceral adiposity, body composition, and metabolic indices. 2,4 Calling attention to how questionable BMI is as a litmus test for obesity are patients classified as overweight or obese (BMI ≥ 25) whose weight, when evaluated by physical

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Use and Misuse of BMI Categories

2023

AMA Journal of Ethics

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Body mass index (BMI) was introduced in the 19th century as a measure of weight relative to height. Before the late 20th century, overweight and obesity were not considered a population-wide health risk, but the advent of new weight loss drugs in the 1990s accelerated the medicalization of BMI. A BMI category labeled obesity was adopted in 1997 by a World Health Organization consultation and subsequently by the US government. Language in the National Coverage Determinations Manual stating that "obesity itself cannot be considered an illness" was removed in 2004, allowing reimbursement for weight loss treatments. In 2013, the American Medical Association declared obesity to be a disease. Yet the focus on BMI categories and on weight loss has yielded few health benefits and contributes to weight-related discrimination and other potential harms.An Important Clinical Problem? Dramatic statements about the health risks of obesity are common today. The opening lines of a recent article read: "Obesity is the most prevalent chronic disease worldwide, affecting approximately 650 million adults. Excess adiposity and its numerous complications, including cardiovascular disease and type 2 diabetes, impose a considerable economic burden and constitute major contributors to global morbidity and mortality." 1 Such assertions are a recent development. According to the Institute of Medicine, "Prior to the late 20th century, overweight and obesity were not considered a population wide health risk." 2 Body weight was often considered as more of a cosmetic and social issue than an important medical concern. 3 A 1969 study found that patients and physicians did not view body weight and weight loss as salient medical problems and considered deviations from weight standards to be almost meaningless. 4 Prior to 2004, the National Coverage Determinations Manual stated bluntly that "obesity itself cannot be considered an illness," 5 and treatment for obesity was not covered by Medicare. 5 The costs of weight loss as a treatment for obesity were not allowed as a medical deduction for tax purposes until 2002. 6 Until the 2010s, in most doctor visits, BMI was not calculated. 7

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Food and Drug Administration's Obesity Drug Guidance Document

Cited by 82 publications

References 37 publications

Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit

Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit

Should Pharmaceuticals Be Used as Weight Loss Interventions for Adolescents Classified as Obese by BMI?

Use and Misuse of BMI Categories

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