Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit

Abstract

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

Racial Disparities in Obesity Treatment

“…Research has shown that pharmacotherapy results can range from very substantial weight loss to modest or no weight loss [72]. The FDA and medical community have been slow to adopt the use of current weight loss medications secondary to a history of harmful medications and their use in the past, such as Fen-Phen, a previously approved combination of fenfluramine and phentermine, which was widely prescribed and caused pulmonary hypertension and heart valvulopathy [73]. Nevertheless, the obesity epidemic necessitates the ongoing consideration of the medical community to consider the proper use of pharmacotherapy in the treatment of obesity.…”

Pharmacologic activation of estrogen receptor α increases mitochondrial function, energy expenditure, and brown adipose tissue

“…Most, if not all, of the pharmacologic agents that reduce body weight are designed to induce satiety (7). Some of the common adverse effects associated with the available antiobesity drugs are hypertension and valve disease (8). Although antiobesity drugs elicit approximately 5% weight reduction, people will not be able to maintain the weight reduction for prolonged periods, highlighting the need for efficacious and safe alternatives (9).…”

The role of gut microbiota in metabolic regulation

“…Ле-чение ожирения и его осложнений занимает одну из гла-венствующих позиций в современной науке, при этом эффективных методов все еще недостаточно [4,5,50]. Изучение микрофлоры кишечника с позиции влияния на ожирение и развития метаболического синдрома только начинается.…”

“…Изменение образа жизни, в том числе ограничение калорийности питания, не всегда приносит желаемый, а главное, стойкий результат [4]. Попытки фармакологической коррекции избыточного веса также не принесли значимого положительного эф-фекта и, кроме того, имели достаточно много побочных эффектов [5]. Неудачи на поприще консервативных ме-тодов лечения ожирения привели к развитию относи-тельно нового направления -бариатрической хирургии, которая дает надежду на радикальное решение проблемы ожирения.…”