Table 1 evoke/evoke+: key eligibility criteria

Male or female aged 55–85 years (both inclusive).

Evidence of neurologic disorders other than AD (e.g. Parkinson’s disease, Lewy body disease, frontotemporal dementia of any type, Huntington’s disease).

Amyloid abnormalities (confirmed by amyloid PET scans [visual read] or CSF Aβ1–42 or CSF Aβ1–42/Aβ1–40; historical data up to 2 years on amyloid abnormalities can be used).

Evidence of a clinically relevant or unstable psychiatric disorder based on Diagnostic and Statistical Manual of Mental Disorders criteria.

MCI or mild dementia of the Alzheimer’s type defined as: CDR global score of 0.5 with a CDR domain score of ≥ 0.5 in at least one of the three instrumental activities of daily living categories, or CDR global score of 1.0, respectively.

MRI or CT scan suggestive of clinically significant structural CNS disease other than the changes allowed for evoke+ (e.g. cerebral large-vessel disease [large vessel (cortical) infarcts > 10 mm in diameter], prior macro-hemorrhage [> 1 cm³], cerebral vascular malformations, cortical hemosiderosis, intracranial aneurism(s), intracranial tumors, changes suggestive of normal pressure hydrocephalus).

For the evoke trial, ARWMC = 3 was also an exclusion criterion.

RBANS delayed memory index score ≤ 85.

Current or previous GLP-1RA treatment in the 90 days prior to screening; regular use (> 2 doses weekly) of anticholinergic medications of moderate or greater potency within 4 weeks of screening; anti-parkinsonian medications within 3 months of screening; anticonvulsants within 3 months of screening; neuroleptics within 3 months of screening; antidepressants without anticholinergic properties of moderate potency or greater where the dose has not been stable for 4 weeks prior to screening (antidepressants are allowed provided stable dose for 4 weeks prior to screening; regular use (> 2 doses weekly) of benzodiazepines and sedatives within 4 weeks of screening; morphine and narcotic analgesics within 3 months of screening. A short use (< 5 days) in relation to surgery or acute injury > 4 weeks before screening is not exclusionary; stimulant medications (e.g. amphetamine, methylphenidate, atomoxetine, modafinil) within 4 weeks of screening; medical marijuana, cannabis and cannabidiol (CBD); any approved or non-approved investigational medicinal product within 90 days before screening or 5 half-lives, whichever is longer.

MMSE score of ≥ 22.

Continuation of approved AD treatments is allowed (must be a stable dose for ≥ 3 months before screening).

In evoke+, participants with significant small vessel disease (defined as ARWMC > 2 and/or > 1 lacunar infarct) are eligible to enroll.

Diagnosis of type 1 diabetes mellitus; personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma; uncontrolled and potentially unstable diabetic retinopathy or maculopathy in patients with T2D; presence or history of malignant neoplasms (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) within 5 years prior to the day of screening; end stage renal disease or chronic or intermittent hemodialysis or peritoneal dialysis; myocardial infarction, stroke, hospitalization for unstable angina pectoris, or transient ischemic attack within 90 days prior to the day of screening; chronic heart failure classified as being in New York Heart Association (NYHA) Class IV at screening; known or suspected hypersensitivity to trial product or related products; female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method; history of major surgical procedures involving the stomach or small intestine potentially affecting absorption of drugs and/or nutrients, as judged by the investigator; clinically significant abnormalities in thyroid function, or clinically significant vitamin B12 or folate deficiency at screening as determined by the investigator (patients with adequately treated thyroid disease [excluding medullary thyroid carcinoma] are eligible); any disorder which in the investigator’s opinion might jeopardize the subject’s safety or compliance with the protocol.