Moving Beyond Inflammation as a Therapeutic Target for Crohn's Disease

Inclusion Criteria: 1. Subjects 18 to 80 years of age, inclusive, at the time of consent 2. Confirmed diagnosis of Crohn's disease based on documented findings on endoscopy and histopathology 3. Active ileal or ileocolonic inflammation on colonoscopy defined as 1\. Ileal SES-CD \> 4 with ulcer subscore \> 1 (ulcers \> 5mm) 4. Failure to respond to (primary or secondary non-response) at least 2 advanced class drugs, without evidence of immunogenicity (anti-TNFa only). Must have been at least 6 months optimized on most recent therapy without corticosteroids. 1. Anti-TNF: Infliximab, Adalimumab, Certolizumab, Golimumab 2. Anti-integrin agent: vedolizumab 3. Anti-IL12/23 agent: Ustekinumab 4. Anti-IL23: Risankizumab, Guselkumab, Mirikizumab 5. JAK inhibitor: Upadacitinib 5. In post surgical patients, must be at least 6 months post-op with endoscopic evidence of ileal disease 6. In females: compliance to recommended birth control requirements Exclusion Criteria: 1. Age \< 18 or \> 80 years 2. Pregnant or Breastfeeding female 3. Diagnosis of ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, diverticular disease-associated colitis, toxic megacolon, active infectious colitis or positive test for Clostridioides Difficile toxin at screening 4. BMI \< 25 5. Current or previous diagnosis of anorexia nervosa 6. Type 1 or Type 2 diabetes 7. Use of concomitant hypoglycemic agents 8. Personal or family history of medullary thyroid carcinoma 9. History of multiple endocrine neoplasia 10. Known serious hypersensitivity to tirzepatide or any of its excipients 11. Have functional or post-operative short-bowel syndrome 12. Had intestinal resection ≤ 24 weeks prior to inclusion or other intra-abdominal surgeries ≤ 12 weeks prior to study inclusion 13. Active treatment with steroids\* 14. Positive stool test for parasites, C. Diff or stool culture for pathologic bacteria within 30 days prior to enrollment 15. Current stricture not passable with an endoscope 16. Impending need for surgery per investigator 17. Have an ileostomy or a colostomy 18. In females: refusal to comply to recommended birth control requirements \*Corticosteroids have metabolic and hormonal effects which we are concerned may interfere with study outcomes and metabolic changes in the population. This exclusion criteria will allow the study population to be standardized across all patients