Retatrutide

Retatrutide (LY-3437943) is an experimental drug for obesity developed by American pharmaceutical company Eli Lilly and Company. It is a triple glucagon hormone receptor agonist (GLP-1, GIP, and GCGR receptors).^[1] It has been shown to achieve a more than 17.5% mean weight reduction in adults without diabetes but with obesity or preobesity (overweight) during a phase 2 trial.^[2][3][4] In the trial, the participants who received the highest dose (12 mg) showed a mean weight reduction of 24.2% after 48 weeks.^[4]

Retatrutide

Clinical data
Other names	LY-3437943
Identifiers
IUPAC name L-tyrosyl-2-methylalanyl-L-glutaminylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-alpha -aspartyl-L-tyrosyl-L-seryl-L-isoleucyl-2-methyl-L-leucyl-Lleucyl-L-alpha -aspartyl-L-lysyl-N6-(N-(19-carboxy-1-oxononadecyl)-L-gamma-glutamyl-2-(2-(2-aminoethoxy)ethoxy)acetyl)-L-lysyl-L-alanyl-L-glutaminyl-2-methylalanyl-L-alanyl-Lphenylalanyl-L-isoleucyl-L-alpha -glutamyl-L-tyrosyl-L-leucyl-L-leucyl-L-alpha -glutamylglycylglycyl-L-prolyl-L-seryl-L-serylglycyl-L-alanyl-L-prolyl-L-prolyl-L-prolyl-L-serinamide
CAS Number	2381089-83-2
UNII	NOP2Y096GV
ChEMBL	ChEMBL5095485

Chemistry

The drug is a peptide with amino acid sequence^[5]

YA¹QGTFTSDYSIL²LDKK⁴AQA¹AFIEYLLEGGPSSGAPPPS³

where superscript numbers refer to unique chemical modifications:

1. "A¹" refers to 2-aminoisobutyric acid (AiB) instead of alanine.
2. "L²" refers to alpha-methyl added to leucine (MeL, 2-methylleucine).
3. "S³" refers to addition of an amino group to the C-terminal serine.
4. "K⁴" refers to a modification group attached to the lysine's tail amine, specifically (AEEA)-gamma-Glu-C20 diacid.