The novel <scp>GIP</scp>, <scp>GLP</scp>‐1 and glucagon receptor agonist retatrutide delays gastric emptying

Urva, Shweta; O’Farrell, Libbey; Du, Yu; Loh, Mei Teng; Hemmingway, Andrea; Qu, Hongchang; Alsina‐Fernandez, Jorge; Haupt, Axel; Miličević, Zvonko; Coşkun, Tamer

doi:10.1111/dom.15167

Cited by 7 publications

(3 citation statements)

References 15 publications

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“…In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight, reaching 24% in the 12-mg dose group (Jastreboff et al, 2023). Retatrutide also slowed gastric emptying of liquids based on the acetaminophen test (Urva et al, 2023).…”

Section: Triple Incretin Agonistmentioning

confidence: 99%

Newer pharmacological interventions directed at gut hormones for obesity

Camilleri,

Acosta

2023

British J Pharmacology

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The objective is to review the newer pharmacological interventions for obesity, specifically single, dual, and triple incretin receptor agonists that are either available or in the pipeline for treatment of obesity. The three incretin receptor targets are glucagon like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic peptide (GIP), and glucagon. There are several approved single or dual incretin agonists which are administered subcutaneously daily (e.g., liraglutide) or weekly (e.g., semaglutide, dulaglutide, and exenatide QW), and experimental dual or triple incretin agonists. Other analogs of amylin, peptide YY, and oxyntomodulin, as well as a combination GLP1R agonist and GIPR antagonist are also being developed. Oral semaglutide (administered daily) is approved for type 2 diabetes and is on track for regulatory review for obesity. The review includes specifically perspectives on the effects of these mechanisms and pharmacological agents on gastric emptying which contribute to satiation and weight loss, in addition to the established evidence on effects on central mechanisms controlling appetite. In the future, it is anticipated that small molecule GLP‐1 receptor agonists (e.g., oral danuglipron) will be developed. These pharmacological agents are having significant impact on glycemic control and obesity and their co‐morbidities.

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Section: Triple Incretin Agonistmentioning

confidence: 99%

Newer pharmacological interventions directed at gut hormones for obesity

Camilleri,

Acosta

2023

British J Pharmacology

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“…6. for GIBAC (Figure 4), can you generate a K d -ranked list of therapeutic candidates which targets X, Y and Z? such as vorolanib [252] or retatrutide [253]? 7. for GIBAC (Figure 4), can you please generate a K d -ranked list of therapeutic small molecule candidates [254,255] which targets X and possesses a K d within a specified K d range, and which does not target Y or Z?…”

Section: Two Future Directions Of Gibac: Ai + Biophysicsmentioning

confidence: 99%

Towards a Truly General Intermolecular Binding Affinity Calculator for Drug Discovery & Design

Li,

Vottevor

2023

Preprint

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Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.

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“…Delayed GE reduces food consumption and therefore leads to weight reduction. 16 The weight-reducing effects of retatrutide have been supported by different clinical trials, presenting compelling evidence. In a randomized, double-blind, and placebo-controlled phase 2 study conducted in the United States, 12 in the 4-mg group (commenced with 4 mg), −16.7% in the 8-mg group (started with 2 mg), −17.9% in the 8-mg group (initiated with 4 mg), and−17.5% in the 12-mg group (commenced with 2 mg), in contrast to a mere −1.6% in the placebo group at the same time point.…”

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confidence: 99%

Unleashing the power of retatrutide: A possible triumph over obesity and overweight: A correspondence

Naeem,

Imran,

Banatwala

2024

Health Science Reports

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Background and AimsOverweight and obesity have become global health challenges with increasing prevalence. Several drugs have received Food and Drug Administration approval for nonsyndromic obesity treatment, but most have limitations, including gastrointestinal side effects and limited weight loss efficacy.BodyRetatrutide, a novel incretin mimetic agent, has shown promise in clinical trials for significant weight reduction. It has demonstrated dosage‐dependent pharmacokinetics with favorable safety profiles. The primary focus of this paper is to explore retatrutide and critically assess its clinical trials to justify its use and feasibility while highlighting its shortcomings. This paper also delves into the subject of obesity and its health manifestations.ConclusionIt is expected that the use of retatrutide, a triple agonist, will result in significant weight loss among individuals who are obese or overweight.

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The novel GIP, GLP‐1 and glucagon receptor agonist retatrutide delays gastric emptying

Cited by 7 publications

References 15 publications

Newer pharmacological interventions directed at gut hormones for obesity

Newer pharmacological interventions directed at gut hormones for obesity

Towards a Truly General Intermolecular Binding Affinity Calculator for Drug Discovery & Design

Unleashing the power of retatrutide: A possible triumph over obesity and overweight: A correspondence

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