Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice?

Abstract

This is a PDF file of an article accepted, but it is not yet the definitive version of record.A new generation of anti-obesity drugs is in development or just arriving on the scene. The first, setmelanotide, has been approved for three ultrarare genetic conditions that cause obesity: proopiomelanocortin deficiency, proprotein convertase subtilisin/kexin type 1 (PCSK1, which encodes an important enzyme in the melanocortin pathway) mutation, and leptin receptor deficiency. Setmelanotide marks the initiation of a personalized medical approach to obesity. The second, 2.4 mg semaglutide once weekly, has been submitted to regulators in the United States and the European Union for approval in overweight patients (body mass index [BMI] >27 kg/m 2 ), and those with both obesity (BMI >30 kg/m 2 ) and at least one weight-related comorbidity. This drug has been studied in five phase 3 clinical trials, four of which are discussed herein: semaglutide produces roughly double the weight loss that typically occurs in patients prescribed older anti-obesity medications. Semaglutide is already approved for treatment of diabetes, and this glucagon-like peptide 1 (GLP-1) receptor analog is part of a class of drugs used widely in diabetes. The third, tirzepatide, is a glucose-insulin peptide and GLP-1 dual agonist in phase 3 trials for obesity management, and the fourth, bimagrumab is a new agent with a unique mechanism of action currently being assessed in phase 2 trials; both are generating much interest. The purpose of this narrative review is to lay the groundwork for a discussion of the clinical impact of these new medications on the clinical management of obesity. Further, we discuss the likely impact of these new anti-obesity medications on the future of obesity pharmacotherapy.

Critical review of bariatric surgical outcomes in patients with Prader‐Willi syndrome and other hyperphagic disorders

“…Rather than the limited duration of weight reduction observed in patients with PWS after bariatric surgery, we continue to advocate an alternative approach, combining supervised reduced‐energy diets with vitamin/mineral supplementation, restricted access to food, and a daily exercise regimen that demonstrates sustained benefits (85). The differences in response to weight‐loss interventions seen among individuals with hyperphagic disorders and recent approval by the United States Food and Drug Administration (FDA) for targeted therapies such as setmelanotide, an MC4R agonist (86), necessitate consideration for genetic screening among people with severe obesity.…”

“…The differences in response to weight-loss interventions seen among individuals with hyperphagic disorders and recent approval by the United States Food and Drug Administration (FDA) for targeted therapies such as setmelanotide, an MC4R agonist(86), necessitate consideration for genetic screening among people with severe obesity.CON CLUS IONA variety of bariatric techniques have been used to address weightrelated comorbidities in patients with PWS and other hyperphagic disorders, with promising short-term results followed by weight recidivism in long-term outcome studies. Given the impact of hyperphagia on the health, quality of life, and life expectancy of the patients, the compilation and publication of comprehensive longterm (>5 years post procedure) outcome data, including weight and medical and nutritional status, are of utmost importance.…”

Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review

“…Tirzepatide is a newer dual agonist of GLP-1 and GIP (gastric inhibitory peptide) which has shown promising anti-obesity effect. ( 30 )…”

Overlooked and under‐evidenced: Community health and long‐term care service needs, utilization, and costs incurred by people with severe obesity

“…45 The increase in remote weight management services resulting from the COVID-19 pandemic may offer future development potential for this under-served population, 46 as do the new wave of effective anti-obesity medications. 47 Importantly for this population, shifting away from a weight-centric approach to one focused on wider person-centred outcomes, 48 including maintaining or achieving functional independence, potentially holds benefit for both individuals and service providers. Training for community staff, who often have sustained input with individuals, but feel ill-equipped to discuss weight, 49 could lead to health gains.…”