72-LB: DD01, a Novel Once-Weekly Dual GLP-1/Glucagon Receptor Agonist, Improves Metabolic Health and Achieves Rapid, Clinically Significant Reductions in Hepatic Steatosis following Only Four Weeks of Treatment and without the Need for Significant Weight Loss in Overweight/Diabetic Subjects with NAFLD

Abstract

DD01 is a dual GLP-1/glucagon receptor agonist acting through two independent pathways to provide rapid resolution of hepatic steatosis, improve glucose control, an reduce body weight in subjects with type 2 diabetes who are obese/overweight and have NAFLD. In a recently completed Phase 1 single and repeat dose safety and pharmacology study, DD01 was well tolerated and improved fasting and fed glucose while providing significant reductions in liver fat as measured by MRI-PDFF. Following only 4 weeks of once-weekly treatment, up to 100% of patients achieved ≥30% reduction in MRI-PDFF. In the high dose group, all subjects achieved at least a 40% reduction in liver fat with a mean reduction of 52% whereas the change from baseline liver fat in the placebo group was only 2.8%. Meaningful and rapid improvements in steatosis were observed at well-tolerated doses that did not cause significant weight loss, thus uncoupling the need for weight loss to precede or coincide with significant improvements in liver health. Disclosure D. To: Employee; Neuraly Inc. J. Shin: Employee; D&D Pharmatech. S. Karanth: None. Y. Lin: None. S. Sosnovtseva: None. A. C. Bell: None.

Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists

“…In a 4‐week phase 1 study, 80 mg s.c. QW for 4 weeks lowered liver fat by 52% while placebo reduced liver fat by only 2.8%, and 100% of individuals treated with the 80 mg dose achieved a ≥30% reduction in liver fat (Table 3C). Adverse effects were consistent with the GLP‐1RA class 97 …”