Glycemic and Weight Loss Effects of GLP-1R Agonist Therapy in Subjects With Spinal Cord Injury and Type 2 Diabetes

Inclusion Criteria:

1. Male and female subjects aged 18-70 years (inclusive) at screening

2. More than one year after spinal cord injury

3. Levels if injury C2-L2 with Asia Impairment Scale A, B, C or D.

4. Provision of signed and dated written informed consent prior to any study specificprocedures

5. Diagnosed with T2DM with glucose control managed with diet and metformin monotherapywhere no significant dose changes (increase or decrease ≥ 50%) have occurred in thethree months prior to screening

6. HbA1c 6.0-9.0% at screening

7. BMI > 22 kg/m2 at screening

8. Female subjects of childbearing potential must have a negative pregnancy test atscreening and randomization, and must not be lactating

9. Females of childbearing potential who are sexually active with a non-sterilized malepartner must use at least one highly effective method of contraception fromscreening and must agree to continue using such precautions through to the end ofthe study. It is strongly recommended for the male partner of a female subject toalso use male condom plus spermicide throughout this period. Cessation ofcontraception after this point should be discussed with a responsible physician.Periodic abstinence, the rhythm method, and the withdrawal method are not acceptablemethods of contraception.

Exclusion Criteria:

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

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

3. Taking mirabegron or other glucose altering medications

4. Taking steroids within the past 1 year

5. Significant anemia (hemoglobin<11g/dL)

6. History of gastric outlet obstruction or chronic diarrhea

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

8. Any subject who has received any of the following medications within the specifiedtime-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 thetime of screening

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

10. 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 toscreening.

11. Significant inflammatory bowel disease or other severe disease or surgery affectingthe upper GI tract (including weight-reducing surgery and procedures) which couldaffect the interpretation of safety and tolerability data

12. Acute or chronic pancreatitis

13. Significant hepatic disease (except for metabolic dysfunction-associatedsteatohepatitis [MASH] or metabolic dysfunction-associated steatotic liver disease [MASLD]) without portal hypertension or cirrhosis) and/or subjects with any of thefollowing results at screening: Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN) Alanine transaminase (ALT) ≥ 3 × ULN Total bilirubin ≥ 2 × ULN

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

15. Unstable angina pectoris, myocardial infarction, transient ischemic attack (TIA) orstroke within 3 months prior to screening, or subjects who have undergonepercutaneous 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

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

17. Basal calcitonin level > 50 ng/L at screening or history/family history of medullarythyroid carcinoma or multiple endocrine neoplasia

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

19. History of HIV infection or other immune compromised disease; and history of organtransplantation

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

21. Patients on ketogenic diet