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Abstract Background Azeliragon, an oral antagonist of the receptor for advanced glycation endproducts (RAGE), was evaluated in an 18‐month Phase 3 study as a treatment for patients with mild Alzheimer’s disease (AD) (the STEADFAST Study). Post‐hoc analyses in a T2D subgroup (HbA1c ≥ 6.5%) found that azeliragon‐treated patients exhibited less cognitive decline (ADAS‐cog11), less whole brain atrophy, less hippocampal atrophy, less ventricular enlargement, and reduced plasma inflammatory cytokine concentrations compared to patients treated with placebo. The current retrospective exploratory analysis was performed to evaluate ADAS‐cog and CDR symptom domains and individual test items to ascertain which were sensitive to treatment effects. Method STEADFAST was a randomized, double‐blind, placebo‐controlled trial in 875 patients with probable mild AD (MMSE 21‐26, CDR global 0.5‐1) receiving stable acetylcholinesterase inhibitors and/or memantine, evaluating the efficacy and safety of 18 months of treatment with azeliragon 5 mg/day relative to placebo. STEADFAST included two separate studies (A‐Study completed as planned, B‐Study prematurely terminated following negative results from the A‐Study) under a single protocol. Patients in the A‐Study with T2D (HbA1c ≥ 6.5%) were analyzed with mean changes from baseline calculated for ADAS‐cog11 and CDR individual item and symptom domain scores. Standard effects sizes were determined using Cohen d. Treatment differences in Month 18 change from baseline were evaluated using both t‐test (presented herein) and Wilcoxon test. Result Forty‐seven patients (26 azeliragon, 21 placebo of whom 19 and 17 had Month 18 data) were analyzed. ADAS‐cog Language and Praxis domains were nominally significantly different favoring azeliragon (p=0.01 and p=0.049, respectively) with Cohen d values of 0.86 and 0.66. A trend for less decline in the Memory domain (p=0.07, effect size 0.62) was noted. No significant differences were noted on CDR cognitive or functional domains. Nominal significant differences favoring azeliragon were noted for ADAS‐cog comprehension (p=0.005, effect size 0.99), ideational praxis (p=0.012, effect size 0.84) and spoken language (p=0.067, effect size 0.62) items and the CDR Memory item (p=0.032, effect size 0.73). Conclusion Results suggest that azeliragon may have benefits over placebo with less decline in memory, language, and praxis over 18 months in patients with mild AD and T2D.