Obesity: The New Global Epidemic Pharmacological Treatment, Opportunities and Limits for Personalized Therapy

Abstract

Background: The increase in global obesity rates over the past three decades has been remarkable, a true epidemic, both in developed and in developing countries. The projections, based on current trends, suggest an increase in the prevalence of obesity at 60% in adult men, 40% in adult women and 25% in children in 2050. Given the limitations of lifestyle and surgery interventions bariatric, drug therapy approaches for the treatment of obesity, therefore become important options. Aim: The purpose of this review is a review of the literature, based on a research on MEDLINE until 2019, on the possible pharmacological options in the treatment of obesity. Results: Currently the FDA has approved several molecules for the treatment of obesity, both in monotherapy and in combination. Pharmacological monotherapies focus mainly on a single protein target and include orlistat, lorcaserin and liraglutide while the combination molecules propose a multi-target approach and include phentermine / topiramate and naltrexone / bupropion. All the approved drugs showed, in the different studies, a weight reduction of at least 5%, compared to placebo, in 52 weeks of observation. Phentermine-topiramate and liraglutide have been associated with the highest probability of at least 5% weight loss. Liraglutide and naltrexone-bupropion had the lowest rates of therapy discontinuation due to adverse events. Conclusion: The drugs, associated with the standard diet and / or exercise protocols, represent a good therapeutic opportunity to allow not only weight loss but also to reduce the risk of developing diseases caused by obesity, particularly cardiovascular diseases, and to maintain the set objectives over time. However, future research on the pharmacological treatment of obesity should encourage greater personalization of therapy, given the differences in safety, efficacy and response to therapy, in the different subpopulations of patients with obesity.

Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota

“…The Report on Nutrition and Chronic Disease Status of Chinese Residents (2020) showed that the overweight and obesity rate of Chinese adult residents exceeded 50%. Based on current trends, the projections suggested an increase in the prevalence of obesity to 40% in adult women, 60% in adult men, and 25% in children by the year 2050 (Milano et al, 2020 ). Obesity is often accompanied by other metabolic diseases, such as hyperlipidemia, hypercholesterolemia, cardiovascular disease, liver steatosis, and type 2 diabetes mellitus (T2DM), all of which increase the risk of death (Mayoral et al, 2020 ).…”

LIFR-α-dependent adipocyte signaling in obesity limits adipose expansion contributing to fatty liver disease

“…An enrichment of immune factors and cells in adipose is associated with obesity, but their role in the development of obesity and the subsequent metabolic sequelae remains less understood (Bischoff et al, 2016;Cohen et al, 2011;Milano et al, 2020;Reilly and Saltiel, 2017;Van Pelt et al, 2017). Since the identification of secreted cytokine mediators of inflammation (e.g., TNFa, IL-1b, and IL-6), there has been an effort to connect signaling between these cytokines and the different cells within adipose tissue including adipocytes and stromal, vascular, and immune cells (Ferrante, 2013;Han et al, 2020;Kosteli et al, 2010;Lumeng et al, 2007aLumeng et al, , 2007bLumeng et al, , 2008.…”

Myeloid‐derived suppressor cells in obesity‐associated periodontal disease: A conceptual model

“…3 People who are considered as obese (ie, have a body mass index of over 30, based upon their weight and height) are at significantly higher risk for many noncommunicable diseases, including cardiovascular diseases, diabetes, musculoskeletal disorders (mainly osteoarthritis), and several cancers. [1][2][3][4] Obesity is a major risk factor for periodontal disease progression, and the precise mechanisms by which obesity-related factors directly influence periodontal disease pathophysiology have not yet been identified. This creates new challenges and therapeutic opportunities in this era of precision medicine, especially in special populations in which many groups present with obesity.…”

“…Changes in dietary and physical activity patterns are often a consequence of environmental and societal changes that can affect specific populations 3 . People who are considered as obese (ie, have a body mass index of over 30, based upon their weight and height) are at significantly higher risk for many noncommunicable diseases, including cardiovascular diseases, diabetes, musculoskeletal disorders (mainly osteoarthritis), and several cancers 1‐4 …”