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LY3437943, LY-3437943
A synthetic peptide acting as a triple agonist for GLP-1, GIP, and glucagon receptors, designed for treating obesity and type 2 diabetes by promoting weight loss and glycemic control.
Thomas. Betsy S BS; Perry. Danielle D; Moe. Samantha S SS; Turgeon. Ricky D RD; Potter. Jen J; Brasc...
The 2023 PEER review lists retatrutide as one of two "up‑and‑coming" drugs, noting it may help with weight loss, but the abstract provides no study results, dosing details, or safety information.
Goetz. Iris A IA; Kanu. Chisom C; Hoover. Anastasia A; Jimenez-Moreno. Cecilia C; Karn. Hayley H; Ki...
Retatrutide, an agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors, is in development for the treatment of obesity. We interviewed participants exiting a phase 2 trial to understand the impact of retatrutide on eating behaviors, physical aspects, emotions, and lifestyle. This was a qualitative exit interview study conducted in the US. Participants were adults with obesity or overweight and weight-related complications exiting the phase 2, double-blind, placebo-controlled trial of retatrutide (1, 4, 8, and 12 mg) (NCT04881760). Telephone interviews were conducted using a semi-structured interview guide. Interviews were recorded, transcribed, and analyzed using ATLAS.ti. Participants (N = 40; mean age 51 years; 52.5 % male) received retatrutide 4/8/12 mg (n = 23), retatrutide 1 mg (n = 13), or placebo (n = 4). Thirty-one of 36 retatrutide-treated participants reported changes in eating behaviors within the trial's first 8 weeks. Participants described eating less often or smaller portions, feeling hungry less often, feeling full after eating, having different food preferences, and feeling more in control of their eating. They also described feeling good about themselves or self-confident (n = 32) and feeling happy (n = 25). Participants reported improvements in mobility or ability to perform physical activities (n = 27), energy levels (n = 24), social activities involving food (n = 18), exercise (n = 19), and leisure activities (n = 17), as well as reduction in clothing size (n = 24). Some retatrutide-treated participants reported reduced participation in social activities due to adverse events (n = 2) or new eating habits (n = 2) and frustration due to disappointing weight loss (n = 3). Thirty of 36 retatrutide-treated participants had weight reduction as a goal, and 76.7 % reported achieving their goal. In this exit interview analysis of adult study participants, those treated with retatrutide reported early changes in eating behavior, improved physical and emotional well-being, and weight reduction goal achievement. Some participants experienced social limitations or frustration due to adverse events or unmet expectations.
Concepción-Zavaleta. Marcio J MJ; Fuentes-Mendoza. Jenyfer M JM; Gonzáles-Yovera. Jhean G...
Obesity is a major driver of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH). As the global prevalence of obesity continues to rise, the burden of MASLD/MASH is increasing, posing significant challenges to healthcare systems. The use of anti-obesity medications (AOMs) in this population is complex due to altered hepatic metabolism, safety concerns, and potential hepatotoxicity. Recent advances in pharmacologic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), dual GLP-1/glucose-gastric inhibitory polypeptide (GIP) agonists, and triple GLP-1/GIP/glucagon agonists, have shown promising metabolic effects in the general population. Among these, GLP-1 RAs (<i>e.g.</i>, liraglutide and semaglutide) consistently demonstrate hepatic benefits, including reductions in hepatic steatosis, improvements in liver enzyme profiles, and attenuation of fibrosis progression. Tirzepatide, a dual GLP-1/GIP agonist, has shown superior weight loss effects compared to GLP-1 receptor agonist monotherapy, with emerging but still limited data on hepatic outcomes in MASLD/MASH. Retatrutide, a triple agonist, has produced the most pronounced metabolic effects to date, although its impact on liver histology remains underexplored. Other AOMs, such as bupropion-naltrexone and phentermine-topiramate, require cautious use due to potential hepatotoxicity. Importantly, advanced MASLD may alter drug pharmacokinetics, underscoring the need for individualized therapy and close monitoring. This review provides an updated synthesis of the efficacy and safety of current and emerging AOMs in patients with MASLD/MASH and highlights the urgent need for further research to define optimal pharmacological strategies in this high-risk population.