Tirzepatide Once Weekly for the Treatment of Obesity

Jastreboff, Ania M.; Aronne, Louis J.; Ahmad, Nadia; Wharton, Sean; Connery, Lisa; Alves, Breno Edson Sendão; Kiyosue, Arihiro; Zhang, Shuyu; Liu, Bing; Bunck, Mathijs C.; Stefański, Adam

doi:10.1056/nejmoa2206038

Cited by 1,193 publications

(1,030 citation statements)

References 28 publications

Supporting

Mentioning

741

Contrasting

Unclassified

Order By: Relevance

“…The compound induces clinically relevant weight loss in patients with T2DM. Remarkably, in individuals with overweight or obesity without T2DM, tirzepatide treatment resulted in a weight loss of 22.5% 157 .…”

Section: Innovative Treatment Approachesmentioning

confidence: 98%

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Körner

Fischer‐Posovszky

2022

Nat Rev Endocrinol

View full text Add to dashboard Cite

Obesity is a multifactorial and complex disease that often manifests in early childhood with a lifelong burden. Polygenic and monogenic obesity are driven by the interaction between genetic predisposition and environmental factors. Polygenic variants are frequent and confer small effect sizes. Rare monogenic obesity syndromes are caused by defined pathogenic variants in single genes with large effect sizes. Most of these genes are involved in the central nervous regulation of body weight; for example, genes of the leptin–melanocortin pathway. Clinically, patients with monogenic obesity present with impaired satiety, hyperphagia and pronounced food-seeking behaviour in early childhood, which leads to severe early-onset obesity. With the advent of novel pharmacological treatment options emerging for monogenic obesity syndromes that target the central melanocortin pathway, genetic testing is recommended for patients with rapid weight gain in infancy and additional clinical suggestive features. Likewise, patients with obesity associated with hypothalamic damage or other forms of syndromic obesity involving energy regulatory circuits could benefit from these novel pharmacological treatment options. Early identification of patients affected by syndromic obesity will lead to appropriate treatment, thereby preventing the development of obesity sequelae, avoiding failure of conservative treatment approaches and alleviating stigmatization of patients and their families.

show abstract

Section: Innovative Treatment Approachesmentioning

confidence: 98%

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Körner

Fischer‐Posovszky

2022

Nat Rev Endocrinol

View full text Add to dashboard Cite

show abstract

“…SURPASS-1 to SURPASS-5 human clinical trials have given favorable results by comparison with similar moieties such as, semaglutide and dulaglutide. The USFDA has approved tirzepatide under the brand name Mounjaro, which has become a revolutionary agent for the management and treatment of T2D and achieving weight loss [29,61,62]. Patient compliance and dose adherence are also favored, since it has the advantage of a once-a-week dose administration.…”

Section: Discussionmentioning

confidence: 99%

“…Due to this unique dual activity property, it is also referred to as 'twincretin'. Subcutaneous administration once a week is adequate, as it possesses a half-life of about 5 days [29].…”

Section: Tirzepatidementioning

confidence: 99%

Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review

Chavda¹,

Ajabiya

Teli

et al. 2022

Molecules

View full text Add to dashboard Cite

The prevalence of obesity and diabetes is an increasing global problem, especially in developed countries, and is referred to as the twin epidemics. As such, advanced treatment approaches are needed. Tirzepatide, known as a ‘twincretin’, is a ‘first-in-class’ and the only dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonist, that can significantly reduce glycemic levels and improve insulin sensitivity, as well as reducing body weight by more than 20% and improving lipid metabolism. This novel anti-diabetic drug is a synthetic peptide analog of the human GIP hormone with a C20 fatty-diacid portion attached which, via acylation technology, can bind to albumin in order to provide a dose of the drug, by means of subcutaneous injection, once a week, which is appropriate to its a half-life of about five days. Tirzepatide, developed by Eli Lilly, was approved, under the brand name Mounjaro, by the United States Food and Drug Administration in May 2022. This started the ‘twincretin’ era of enormously important and appealing dual therapeutic options for diabetes and obesity, as well as advanced management of closely related cardiometabolic settings, which constitute the leading cause of morbidity, disability, and mortality worldwide. Herein, we present the key characteristics of tirzepatide in terms of synthesis, structure, and activity, bearing in mind its advantages and shortcomings. Furthermore, we briefly trace the evolution of this kind of medical agent and discuss the development of clinical studies.

show abstract

“…However, new opportunities are on the horizon. Both sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce progressive renal failure in patients with/without diabetes [22] , thus directly reducing the risk outlined in the recent metaanalysis [11] . However, both GLP-1RAs and dual GLP-1/GIP RAs also have an impressive activity on weight loss.…”

mentioning

confidence: 99%