Radar des Essais Cliniques

History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures.

Any subject who has received another investigational product as part of a clinical study within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening

Taking mirabegron or other glucose altering medications

Taking steroids within the past 1 year

Significant anemia (hemoglobin<11g/dL)

History of gastric outlet obstruction or chronic diarrhea

History of a chronic neurological illness other than SCI (i.e.; MS, etc)

Any subject who has received any of the following medications within the specified time-frame prior to the start of the study

• Herbal preparations or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion-naltrexone, phentermine-topiramate, phentermine, lorcaserin) within a year prior to the start of the study
• Pioglitazone, SGLT2 or DPPIV inhibitors, GLP-1RA within the last 60 days at the time of screening

Severe allergy/hypersensitivity to any of the proposed study treatments, excipients, acetaminophen

Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus (T1DM) or diabetic ketoacidosis, or if the subject has been treated with daily SC insulin within 90 days prior to screening.

Significant inflammatory bowel disease or other severe disease or surgery affecting the upper GI tract (including weight-reducing surgery and procedures) which could affect the interpretation of safety and tolerability data. Prior history of bariatric surgery is not considered exclusion given the ample evidence of safety of use of GLP-1R therapy in this population.

Acute or chronic pancreatitis

Significant hepatic disease (except for metabolic dysfunction-associated steatohepatitis [MASH] or metabolic dysfunction-associated steatotic liver disease [MASLD]) without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:

Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN) Alanine transaminase (ALT) ≥ 3 × ULN Total bilirubin ≥ 2 × ULN

Impaired renal function defined as estimated glomerular filtration rate (eGFR) < 45 mL/minute/1.73m2 at screening (GFR estimated according to Modification of Diet in Renal Disease (MDRD) using MDRD Study Equation IDMS-traceable [SI units])

Unstable angina pectoris, myocardial infarction, transient ischemic attack (TIA) or stroke within 3 months prior to screening, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening

Severe congestive heart failure (New York Heart Association Class III or IV)

Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia

History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer

History of HIV infection or other immune compromised disease; and history of organ transplantation

Substance dependence or history of alcohol abuse and/or excess alcohol intake

Patients on ketogenic diet