1253-OR: ADA Presidents' Select Abstract: Efficacy and Safety of Orforglipron vs. Placebo Added to Titrated Insulin Glargine in Adults with Long-Standing Type 2 Diabetes: ACHIEVE-5

Introduction and Objective: The efficacy and safety of the daily oral, non-peptide GLP-1RA orforglipron (OFG) were assessed as add-on to insulin glargine with/without metformin and/or SGLT-2 inhibitors in adults with type 2 diabetes (T2D) (ACHIEVE-5; NCT06109311). Methods: In this 40-week double-blind, randomized, placebo-controlled, phase 3 study, participants with T2D and inadequate glycemic control were randomized (1:1:1:1) to receive daily OFG (3, 12, or 36 mg) or placebo (PBO). The primary endpoint was change from baseline in HbA1c at week 40 (superiority for 12 and/or 36 mg). Results are presented for the efficacy estimand. Results: 546 participants (age 60.2 years; T2D duration 15.0 years; HbA1c 8.5% [69.4 mmol/mol]; BMI 30.8 kg/m2) were randomized. At week 40, all OFG doses were superior to PBO in the primary and all key secondary endpoints (all p