This review investigates the side effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide, semaglutide, and tirzepatide, medications known for their efficacy in promoting weight loss among individuals with obesity. The rationale is rooted in understanding the balance between their therapeutic benefits and associated risks. This was a comprehensive clinical review, including systematic reviews, meta-analyses, randomized controlled trials (RCTs), and cohort studies. Data were extracted from databases such as PubMed, Scopus, Embase, MEDLINE, and Google Scholar, focusing on the tolerability, severity, and risks of these medications. GLP-1RAs demonstrated significant weight loss outcomes. In clinical trials, liraglutide showed a placebo-corrected weight loss of around 5 %, semaglutide 12 %, and tirzepatide 18 %. Common side effects were predominantly gastrointestinal, including nausea, diarrhea, constipation, and vomiting. Rare serious adverse events included gallbladder disorders and acute pancreatitis. In, addition, multiple studies identify new risks associated with GLP-1RAs including increased aspiration risk during anesthesia due to delayed gastric emptying and challenges with bowel preparation for colonoscopies. While GLP-1RAs are effective in managing obesity, their use is associated with gastrointestinal side effects and rare but serious adverse events. The findings underscore the importance of individualized dosing and thorough patient assessment. Continuous research and vigilant monitoring are essential to optimize their safe use. Further studies are needed to refine guidelines, particularly regarding new concerns such as delayed gastric emptying and its implications for anesthesia.

Peptide YY_3-36 is a satiation hormone released postprandially into the bloodstream from L-endocrine cells in the gut epithelia. In the current report, we demonstrate PYY_3-36 is also present in murine as well as in human saliva. In mice, salivary PYY_3-36 derives from plasma and is also synthesized in the taste cells in taste buds of the tongue. Moreover, the cognate receptor Y2R is abundantly expressed in the basal layer of the progenitor cells of the tongue epithelia and von Ebner's gland. The acute augmentation of salivary PYY_3-36 induced stronger satiation as demonstrated in feeding behavioral studies. The effect is mediated through the activation of the specific Y2 receptor expressed in the lingual epithelial cells. In a long-term study involving diet-induced obese (DIO) mice, a sustained increase in PYY_3-36 was achieved using viral vector-mediated gene delivery targeting salivary glands. The chronic increase in salivary PYY_3-36 resulted in a significant long-term reduction in food intake (FI) and body weight (BW). Thus this study provides evidence for new functions of the previously characterized gut peptide PYY_3-36 suggesting a potential simple and efficient alternative therapeutic approach for the treatment of obesity.

Obesity is a multifactorial disease with a variable and underwhelming weight loss response to current treatment approaches. Precision medicine proposes a new paradigm to improve disease classification based on the premise of human heterogeneity, with the ultimate goal of maximizing treatment effectiveness, tolerability, and safety. Recent advances in high-throughput biochemical assays have contributed to the partial characterization of obesity's pathophysiology, as well as to the understanding of the role that intrinsic and environmental factors, and their interaction, play in its development and progression. These data have led to the development of biological markers that either are being or will be incorporated into strategies to develop personalized lines of treatment for obesity. There are currently many ongoing initiatives aimed at this; however, much needs to be resolved before precision obesity medicine becomes common practice. This review aims to provide a perspective on the currently available data of high-throughput technologies to treat obesity.

Chronic non-communicable diseases (CNCD) represent a major cause of morbidity and mortality. Type 2 diabetes mellitus (T2DM) is one of the most prevalent CNCD that is associated with a significant medical and economic burden. One of the main modifiable risk factors of T2DM is obesity. Many medications used for T2DM can lead to weight gain, worsening one of the root causes of this disease. In this clinical review, we study the effect of medications for T2DM on body weight. We used MEDLINE, Google scholar, PubMed, Scopus, and Embase databases to search for relevant studies between 1 January 1950 to 20 September 2022 in English language. Here, we review the most prescribed medications for T2DM and summarize their effect on patients’ body weight. We will also present an expert opinion on a recommended weight-centric approach to treat T2DM. Multiple T2DM medications have been associated with weight gain. Insulin, sulfonylureas, thiazolidinediones and meglitinides may increase body weight. However, biguanides (e.g., metformin), glucagon-like peptide-1 agonists (e.g., semaglutide, liraglutide, tirzepatide), sodium-glucose cotransporter 2 inhibitors, and amylin analogs (e.g., pramlintide) are associated with significant weight loss. Dipeptidyl peptidase-4 inhibitors are considered weight neutral medications. Experts in the fields of endocrinology and obesity recommend utilizing a weight-centric approach when treating T2DM. Considering the high prevalence and debilitating complication of T2DM, it is of utmost importance to shift from a weight gain approach (i.e., insulin, sulfonylureas) into a weight loss/neutral one (i.e., GLP-1 agonists, SGLT-2 inhibitors, metformin).