Abstract
The worldwide upward trend in obesity in adults and the increased incidence of overweight children suggests that the future risk of obesity-related illnesses will be increased. The existing anti-obesity drugs act either in the central nervous system (CNS) or in the peripheral tissues, controlling the appetite and metabolism. However, weight regain is a common homeostatic response; current anti-obesity medications show limited effectiveness in achieving long-term weight loss maintenance; in addition to being linked to various side effects. Combined anti-obesity medications (per os or injectable) target more than one of the molecular pathways involved in weight regulation, as well as structures in the CNS. In this systematic review, we conducted a search of PubMed and The ClinicalTrials.gov up to February 2021. We summarized the Food and Drug Administration (FDA)-approved medications, and we focused on the combined pharmacological treatments, related to the incretin hormones, currently in a clinical trial phase. We also assessed the mechanism of action and therapeutic utility of these novel hybrid peptides and potential interactions with other regulatory hormones that may have beneficial effects on obesity. As we improve our understanding of the pathophysiology of obesity, we hope to identify more novel treatment strategies.
Highlights
IntroductionObesity is a chronic metabolic disease, which can be defined as an excessive accumulation of body fat that leads to increased morbidity and mortality
Out of 492, we evaluated only 56 clinical trials that provided available published results and were related to anti-obesity medications and incretin hormones
2020, Lorcaserin was withdrawn from the US market, as clinical trials showed an increased occurrence of malignancies [11]
Summary
Obesity is a chronic metabolic disease, which can be defined as an excessive accumulation of body fat that leads to increased morbidity and mortality. Obesity has been shown to increase the risk of various medical conditions, such as diabetes mellitus type 2, cardiovascular disease, gallbladder disease, nonalcoholic fatty liver disease, several types of malignancies (i.e., in colon, endometrium, breast, esophagus, kidney), osteoarthritis, obstructive sleep apnea, and mental health problems, leading to increased morbidity and mortality [1]. The worldwide prevalence of obesity has nearly tripled between 1975 and 2016 and continues to rise at an alarming rate, rendering it a global pandemic [2].
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