88-OR: Long-Acting Amylin Analog AZD6234 in Combination with the GLP-1R Agonist Semaglutide Enhances Body Weight and Fat Mass Loss in Diet-Induced Obese (DIO) Rats

by sugaradmin



Introduction and Objective: AZD6234, a long-acting amylin analog in clinical development for weight management, reduces body weight (BW) in diet-induced obese (DIO) rats without a loss of lean mass. Semaglutide, a GLP-1R agonist, reduces BW with both fat mass and lean mass loss. Here, we aim to understand the impact of combined treatment of AZD6234 and semaglutide on body composition in DIO rats.Methods: Male Sprague Dawley DIO rats were injected QD SC with either vehicle, AZD6234 7.5 nmol/kg, semaglutide 5 nmol/kg or both for 28 days. Monotherapy doses were selected to achieve matching BW loss. BW and food intake were measured daily, and body composition was measured at baseline and end of study.Results: Treatment with AZD6234 or semaglutide led to an inhibition of food intake of ~-20 %, p<0.0001 compared to vehicle, while the combined treatment had an additive effect of -41%, p<0.0001. Treatment with AZD6234 or semaglutide showed similar BW loss (-9.3% and -9.9%, respectively) compared to vehicle (p<0.0001). Combined treatment resulted in an additive BW loss of -19.1%, p<0.0001. Vehicle-treated rats gained +22.8 g of fat mass and +9.9 g of lean mass from baseline. AZD6234 treated rats lost more fat mass than with semaglutide (-17.7 g, p<0.0001 and -11.4 g, p=0.0001, respectively), while combined treatment led to a loss of fat mass more than the sum of both monotherapies (-34.7 g, p<0.0001). AZD6234 treatment led to a preservation of lean mass (17.9 g, ns compared to vehicle), while both semaglutide (-0.3 g) and combined treatment (-4.7 g, p=0.0215) did not.Conclusion: Treatment with AZD6234 and semaglutide showed similar BW loss, but AZD6234 treatment led to more fat mass loss with the preservation of lean mass. Combined treatment led to additive effects on suppression of food intake, BW and fat mass loss.

Disclosure

G. Geoghegan: None. J.D. Brown: None. K.M. Mather: None. S. Will: Employee; AstraZeneca. S. Omar: Employee; AstraZeneca. D. Baker: Employee; AstraZeneca. D.C. Hornigold: Employee; AstraZeneca. Stock/Shareholder; AstraZeneca.



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