338-OR: Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People with T2D

Tirzepatide (TZP) , a dual GIP and GLP-1 receptor agonist (RA) has shown superior improvement in glycemic control and body weight than selective GLP-1 RA. Rodent models indicate that GIP RA augments GLP-1 RA induced food intake suppression and causes body weight loss, mainly by reducing fat mass. This randomized, double-blind, parallel study compared the effects of TZP 15 mg (N=45) , semaglutide (SEMA) 1 mg (N=44) and placebo (PBO) (N=28) on energy intake (assessed by an ad libitum lunch) , appetite (visual analog scale [VAS] ratings of hunger, satiety, prospective food consumption [PFC], and fullness) and body composition (air displacement plethysmography) at baseline and at 28 weeks of treatment. At 28 weeks, reductions in body weight from baseline were observed with TZP 15 mg (-11.2 kg) and SEMA 1 mg (-6.9 kg) , and significantly differed between treatment groups (-4.3 kg [95% confidence interval [CI]: -6.8, -1.9]; p<0.001) . Reductions in fat mass from baseline were also observed with TZP 15 mg (-9.7 kg) and SEMA 1 mg (-5.9 kg) , and significantly differed between treatment groups (-3.8 kg [95% CI: -6.2, -1.4]; p=0.002) . Energy intake reductions from baseline observed with TZP 15 mg (-348.4 kcal) and SEMA 1 mg (-284.1 kcal) did not differ between treatment groups (-64.3 kcal [95% CI: -160.3, 31.7]; p=0.187) . TZP reduced overall appetite by increasing satiety with decreased PFC (all p<0.05) . Appetite ratings did not differ between TZP and SEMA. In conclusion, TZP achieved greater weight loss than selective GLP-1 RA, mostly driven by fat mass loss. Significant and clinically meaningful reductions in appetite and energy intake were observed with both TZP and selective GLP-1 RA. However, these effects could not totally explain the additional weight loss with TZP. As appetite and energy intake reduction were not significantly different between treatments; additional mechanisms might contribute to the weight loss with TZP. Ongoing studies will further elucidate the mechanism of weight loss with TZP. Disclosure T.Heise: Advisory Panel; Novo Nordisk A/S, Research Support; ADOCIA, AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Genova, Nestlé, Neuraly Inc., Novo Nordisk A/S, Sanofi, Zealand Pharma A/S, Speaker's Bureau; Eli Lilly and Company, Gan & Lee Pharmaceuticals, Novo Nordisk A/S. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. Z.Milicevic: Employee; Eli Lilly and Company. J.De vries: Advisory Panel; ADOCIA, Novo Nordisk A/S, Zealand Pharma A/S, Speaker's Bureau; Novo Nordisk A/S. T.Coskun: Employee; Eli Lilly and Company. S.Urva: Employee; Eli Lilly and Company. J.Li: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.J.Pratt: Employee; Eli Lilly and Company. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. K.J.Mather: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.P.Dunn: Employee; Eli Lilly and Company, Eli Lilly and Company. Funding Eli Lilly and Company