A narrative review of approved and emerging anti-obesity medications.

Background: Recently, many drugs have been approved for halting overweight and obesity-few types of research shifted to using Anti-obesity medications (AOM) solely for well-being and shape-keeping. Objective: This narrative review's objective was to explore the use of AOM in relation to their medical indications, efficacy, and cardiovascular safety. Methods and materials: We have conducted a narrative review of the literature on approved/non-approved AOM used for obesity and overweight. We have shed light on the emerging trials of therapies and evolving remedies. Results: Recently, there has been an enormous change in the use of AOM with high consumption that deserves extensive surveillance for the long-term consequences and impact on social, mental, and physical health. Nearly six AOMs and combined therapy are approved by the Food and Drug Administration. The recent guidelines for obesity management have shifted the focus from weight loss to goals that the patient considers essential and toward targeting the root cause of obesity. Conclusion: The use of AOM increased enormously despite its sometimes-dubious safety and ineffectiveness. The public and medical professionals should be vigilant to the real-world benefits of anti-obesity drugs and their achieved effectiveness with an improved safety profile.

GLP-1 and weight loss: unraveling the diverse neural circuitry.

Glucagon-like peptide-1 (GLP-1) is currently one of the most promising biological systems for the development of effective obesity pharmacotherapies. Long-acting GLP-1 analogs potently reduce food intake and body weight, and recent discoveries reveal that peripheral administration of these drugs reduces food intake largely through humoral pathways involving direct action on brain GLP-1 receptors (GLP-1R). Thus, it is of critical importance to understand the neural systems through which GLP-1 and long-acting GLP-1 analogs reduce food intake and body weight. In this review, we discuss several neural, physiological, cellular and molecular, as well as behavioral mechanisms through which peripheral and central GLP-1R signaling reduces feeding. Particular attention is devoted to discussion regarding the numerous neural substrates through which GLP-1 and GLP-1 analogs act to reduce food intake and body weight, including various hypothalamic nuclei (arcuate nucleus of the hypothalamus, periventricular hypothalamus, lateral hypothalamic area), hindbrain nuclei (parabrachial nucleus, medial nucleus tractus solitarius), hippocampus (ventral subregion; vHP), and nuclei embedded within the mesolimbic reward circuitry [ventral tegmental area (VTA) and nucleus accumbens (NAc)]. In some of these nuclei [VTA, NAc, and vHP], GLP-1R activation reduces food intake and body weight without concomitant nausea responses, suggesting that targeting these specific pathways may be of particular interest for future obesity pharmacotherapy. The widely distributed neural systems through which GLP-1 and GLP-1 analogs act to reduce body weight highlight the complexity of the neural systems regulating energy balance, as well as the challenges for developing effective obesity pharmacotherapies that reduce feeding without producing parallel negative side effects.

Effect of Liraglutide on Fat Mass Percentage Among Overweight and Obese Adults with Type 2 Diabetes: A Systematic Review.

Background: Obesity and type 2 diabetes mellitus (T2DM) are two global public health problems. Liraglutide, a glucagon-like peptide 1 analogue (GLP-1), is considered an effective option for weight loss. Hence, it is meaningful to understand the impact of GLP-1 therapy on body composition, particularly fat mass percentage (%), in determining health risks associated with obesity. The current meta-analysis and systematic review aimed to appraise and summarize available studies regarding the efficacy of liraglutide on fat mass (%), anthropometrics and glycemic control. Methods: Three databases were searched up to March 2022 for randomized clinical trials (RCTs) and studies that evaluated the efficacy of liraglutide on T2DM patients: Cochrane Central Register of Controlled Trials, Web of Science, and PUBMED: Cochrane Central Register of Controlled Trials, Web of Science, and PUBMED. If at least two studies had the same outcome and treatment, a random effect model meta-analysis was used to report pooled mean difference (MD) and 95% confidence interval (CI). The protocol of this review was registered in PROSPERO under registration number CRD42022313002. Results: From the 4031 articles identified and reviewed, only 5 studies (N = 263 patients) matched the inclusion criteria. Only two out of 3 RCTs have complete data to produce forest plots. No significant changes were observed from the pooled MD for body fat % [-0.56 (-2.63, 1.26)] and weight [-0.68 (-2.63, 1.26)]. A significant change in Hba1c with a pooled MD of -1.25 (-2.13, -0.36) (p = 0.006) was observed. I2 tests were above the threshold of 50% for weight and Hba1c, indicating heterogeneity among the included studies. Conclusion: This review suggests that liraglutide is effective in glycemic control with no significant effect on weight and fat mass % among overweight patients with T2DM. It is important to note, however, that the certainty of the available evidence is weak.

Weight Loss of Over 100 lbs in a Patient of Prader-Willi Syndrome Treated With Glucagon-Like Peptide-1 (GLP-1) Agonists.

Prader-Willi syndrome (PWS) is the most common genetic obesity syndrome. The clinical features of this condition include childhood obesity, hyperphagia, infantile hypotonia, hypogonadism, short stature, and characteristic facial features. The leading cause of morbidity and mortality in PWS is hyperphagia and resultant obesity. Here, we highlight the effectiveness of glucagon-like peptide-1 (GLP-1) agonists by reporting an interesting case of successful rapid weight loss in an adult with PWS using GLP-1 agonists - exenatide and liraglutide. To the best of our knowledge, this report presents the first clinical evidence supporting the use of GLP-1 receptor agonists in the treatment of genetic obesity syndromes; our patient lost a total of 125 lbs on GLP-1 analog and continues to lose weight.

Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety.

Liraglutide and other agonists of the glucagon-like peptide 1 receptor (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. GLP-1RAs inhibit hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc) but only indirectly, implicating synaptic afferents to AgRP neurons. To investigate, we developed a method combining rabies-based connectomics with single-nuclei transcriptomics. Applying this method to AgRP neurons in mice predicts 21 afferent subtypes in the mediobasal and paraventricular hypothalamus. Among these are Trh+ Arc neurons (TrhArc), which express the Glp1r gene and are activated by the GLP-1RA liraglutide. Activating TrhArc neurons inhibits AgRP neurons and decreases feeding in an AgRP neuron-dependent manner. Silencing TrhArc neurons increases feeding and body weight and reduces liraglutide's satiating effects. Our results thus demonstrate a widely applicable method for molecular connectomics, reveal the molecular organization of AgRP neuron afferents, and shed light on a neurocircuit through which GLP-1RAs suppress appetite.

First Reported Case of Dulaglutide-Induced Acute Pancreatitis With Normal Serum Lipase Level.

Dulaglutide is being extensively used for non-insulin-dependent diabetes mellitus and congestive heart failure and is also being used as an off-label weight loss aid. Due to its wide use, we had to shed some light on this rare finding of normal lipase level in a patient with signs and symptoms suggestive of acute pancreatitis. A high index of clinical suspicion for acute pancreatitis despite normal lipase should warrant a low threshold for radiological imaging to rule it out.

Liraglutide Overdose-Induced Acute Pancreatitis.

Liraglutide, a long-acting cardioprotective glucagon-like peptide (GLP)-1 analog, is effective for medical weight loss and glycemic control in type 2 diabetes. It is generally well tolerated with mild side effects. There are few reports on complications from Liraglutide overdose. The aim of this paper is to report the case of a 25-year-old healthy female who presented with acute pancreatitis secondary to Liraglutide overdose and to review the current literature on Liraglutide used for obesity management. The current literature examining the association between acute pancreatitis and Liraglutide use, and Liraglutide overdose are inconclusive. Further research is recommended.

FDA-Approved Pharmacotherapy for Weight Loss Over the Last Decade.

Obesity is a recently defined illness whose diagnosis and treatment continue to be stigmatized. Currently, due to lifestyle changes brought on by technological advancements and the wide availability and affordability of high-calorie foods, millions of people around the world suffer from obesity and/or its sequelae. Finding adequate prevention and treatment options would therefore lead to massive improvements in the duration and quality of life of affected individuals. In this review, we searched the PubMed database for studies exploring the safety and efficacy of the five medications currently approved by the FDA for the treatment of obesity. We included only studies pertaining to adult patients that have been published between 2012 and 2022. We found evidence that all the drugs analyzed such as orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, and semaglutide appear to be effective in inducing weight loss, with the suggestion that semaglutide may have superior efficacy. However, a massive obstacle in developing treatment guidelines remains the lack of prolonged studies monitoring the long-term safety and efficacy of obesity medications. Nevertheless, in patients at risk of complications from obesity, the benefits of losing fat mass may outweigh the potential side effects associated with these medications and clinicians should prescribe whichever of the FDA-approved pharmacotherapy they deem most appropriate for the patient's specific set of circumstances.

Effectiveness and cost of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in obesity services (STRIVE study): study protocol of an open-label, real-world, randomised, controlled trial.

INTRODUCTION: In the UK and Ireland, severe and complex obesity is managed in specialist weight management services (SWMS), which provide multicomponent lifestyle interventions to support weight loss, and use of medication if available. Liraglutide 3 mg (LIRA 3 mg) is an effective weight-loss medication, but weight loss in individual patients is variable, and its efficacy has not been assessed in SWMS. This study aims to investigate whether a targeted prescribing pathway for LIRA 3 mg with multiple prespecified stopping rules could help people with severe obesity and established complications achieve ≥15% weight loss in order to determine whether this could be considered a clinically effective and cost-effective strategy for managing severe and complex obesity in SWMS. METHODS AND ANALYSIS: In this 2-year, multicentre, open-label, real-world randomised controlled trial, 384 adults with severe and complex obesity (defined as body mass index ≥35 kg/m2 plus either prediabetes, type 2 diabetes, hypertension or sleep apnoea) will be randomised via a 2:1 ratio to receive either standard SWMS care (n=128) or standard SWMS care plus a targeted prescribing pathway for LIRA 3 mg with prespecified stopping rules at 16, 32 and 52 weeks (n=256).The primary outcome is to compare the proportion of participants achieving a weight loss of ≥15% at 52 weeks with a targeted prescribing pathway versus standard care. Secondary outcomes include a comparison of (1) the weight loss maintenance at 104 weeks and (2) the budget impact and cost effectiveness between the two groups in a real-world setting. ETHICS AND DISSEMINATION: The Health Research Authority and the Medicines and Healthcare products Regulatory Authority in UK, the Health Products Regulatory Authority in Ireland, the North West Deanery Research Ethics Committee (UK) and the St Vincent's University Hospital European Research Ethics Committee (Ireland) have approved the study. The findings of the study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov-Identifier: NCT03036800.European Clinical Trials Database-Identifier: EudraCT Number 2017-002998-20.

Can we win the war on obesity with pharmacotherapy?

INTRODUCTION: Obesity is a major health concern for several countries. The United States (U.S.) has arguably led the world in the percentage of overweight and/or obese per capita for several decades. As a result, numerous FDA-approved pharmacotherapeutic options are available for the long-term treatment of obesity. Although most of these medications have been on the U.S. market for a few years and have demonstrated efficacy for long-term weight loss in clinical trials, the impact of these medications on obesity in the U.S. has yet to be realized. Areas covered: We will review and evaluate why pharmacotherapy for obesity has not produced a meaningful reduction in the number of overweight and obese adults in the U.S. Expert commentary: Several obstacles, such as adverse drug effects, poor insurance coverage, not treating obesity as a chronic disease, and availability of other weight loss alternatives, has resulted in poor performance of pharmacotherapy for obesity in the U.S. market.