Pharmacologic therapy of obesity: mechanisms of action and cardiometabolic effects

Abstract

Obesity is a chronic, relapsing, multifactorial disease, which has become a serious threat to public health globally, as the worldwide prevalence of obesity increases exponentially over time. It has been well established that obesity is associated with multiple adverse cardiometabolic effects. Although lifestyle changes are the first line of therapy for obesity, these are often insufficient in attaining weight loss goals.Orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion, and liraglutide are agents that have been approved for the treatment of obesity but their effects on cardiometabolic risk factors and outcomes have not been clearly elucidated. Given the detrimental repercussions of obesity on cardiometabolic health, there is a pressing clinical need to fully understand the effects of these agents beyond weight loss alone. Certain previous weight loss drugs have been withdrawn due to safety concerns and this underlines the need for more careful assessment of the effects of the various pharmacologic agents currently used for the treatment of obesity. This review aims to provide an overview of the mechanisms, efficacy, safety and cardiometabolic effects of the currently available pharmacologic agents for weight loss.

Suppression of Lipid Accumulation in 3T3-L1 Adipocytes by α-Tocopheryl Succinate

“…Several compounds such as phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide, have been approved by the United States Food and Drug Administration to treat obesity. 2) The norepinephrine transporter inhibitor phentermine suppresses appetite by activating hypothalamic proopiomelanocortin arcuate nucleus neurons. Topiramate is an antiepileptic drug that also suppresses appetite by modulating activity of voltage-gated ion channels.…”

Microbiota-Mitochondria Inter-Talk: A Potential Therapeutic Strategy in Obesity and Type 2 Diabetes

“…Growing evidence suggests that fecal microbiota transplantation (FMT) is a valuable and promising therapeutic option for diabetes and obesity disorders [ 131 ]. FMT showed beneficial effects by attenuating the pancreatic islet β-cell destruction and improving the insulin resistance in T2D patients [ 131 , 132 ], as well as reducing the low-grade chronic inflammation caused by a microbiota imbalance [ 131 ]. Moreover, a recent study by Who et al showed that altered gut microbiota mediates some of the antidiabetic effects of metformin, a drug widely used in T2D that inhibits complex I and enhances the ADP:ATP ratio, thereby activating liver AMPK to slow liver gluconeogenesis [ 133 ].…”

Tea polyphenols attenuate liver inflammation by modulating obesity-related genes and down-regulating COX-2 and iNOS expression in high fat-fed dogs

“…The most effective treatment for obesity prevention is dietary control and physical exercise-based therapies combined with pharmacological therapies, as well as bariatric surgery, but different lifestyles do not allow most people access to proper obesity therapy [7,8]. In contrast, many pharmacological therapies are available for obesity treatment, but their outcome is very limited and can involve many side effects [9]. Therefore, controlling obesity, a major cause of inflammation and cancer, with natural products and herbs has become increasingly popular [10].…”