Oral semaglutide provides limited benefit in individuals with early AD

The use of oral semaglutide does not reduce the speed of clinical progression in individuals with early Alzheimer's disease (AD), according to the results to two phase III trials.

Conducted across 566 sites in 40 countries, the evoke and evoke+ trials evaluated the efficacy and safety of oral semaglutide up to 14 mg once daily in individuals with amyloid-confirmed AD who were between 55 and 85 years of age and had mild cognitive impairment or mild dementia due to AD. In evoke+, those with significant small vessel pathology were included.

A total of 3,808 individuals (mean age 72.2 years) participated in the study, including 1,855 in evoke and 1,953 in evoke+ (2.8 percent had small vessel pathology). These participants were randomly assigned to receive once-daily semaglutide 14 mg (flexible dose) (928 in evoke, 976 in evoke+) or placebo (927 in evoke, 977 in evoke+) for up to 156 weeks.

The primary endpoint was change from baseline in Clinical Dementia Rating—Sum of Boxes (CDR-SB) score at week 104.

The mean baseline CDR-SB score overall was 3.7. At week 104, CDR-SB score increased by 2.3 with semaglutide vs 2.3 with placebo in evoke (estimated difference, −0.08, 95 percent confidence interval [CI], −0.35 to 0.20; p=0.57) and by 2.2 vs 2.1, respectively, in evoke+ (estimated difference, 0.10, 95 percent CI, −0.17 to 0.38; p=0.46).

Treatment-emergent adverse events occurred in 91.2 percent of semaglutide-treated participants and 84.4 percent of placebo-treated participants. There were five deaths considered to be related to treatment by the investigators, including one in the semaglutide group and four in the placebo group.