GLP-1 based therapies and disease course of inflammatory bowel disease

Marie Villumsen; Astrid Blicher Schelde; Espen Jimenez-Solem; Tine Jess; Kristine Højgaard Allin

doi:10.1016/j.eclinm.2021.100979

GLP-1 based therapies and disease course of inflammatory bowel disease

EClinicalMedicine. 2021 Jun 23:37:100979. doi: 10.1016/j.eclinm.2021.100979. eCollection 2021 Jul.

Authors

Marie Villumsen¹, Astrid Blicher Schelde², Espen Jimenez-Solem^{2

3}, Tine Jess⁴, Kristine Højgaard Allin⁴

Affiliations

¹ Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
² Department of Clinical Pharmacology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.
³ Copenhagen Phase IV unit (Phase4CPH), Department of Clinical Pharmacology and Center of Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
⁴ Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.

Abstract

Background: The disease course of inflammatory bowel disease (IBD) following treatment with glucagon-like peptide (GLP)-1 based therapies is unclear. The aim of this study was to examine the disease course of IBD in patients treated with GLP-1 based therapies compared with treatment with other antidiabetics.

Methods: Using nationwide Danish registries, we identified patients with IBD and type 2 diabetes who received antidiabetic treatment between 1 January 2007 and 31 March 2019. The primary outcome was a composite of the need for oral corticosteroids, tumour necrosis factor-α inhibitors, IBD-related hospitalisation, or IBD-related surgery. In the setting of a new-user active comparator design, we used Poisson regression to estimate incidence rate ratios (IRR) comparing treatment with GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors with other antidiabetic therapies. The analyses were adjusted for age, sex, calendar year, IBD severity, and metformin use.

Findings: We identified 3751 patients with a diagnosis of IBD and type 2 diabetes and with a prescription of an antidiabetic drug (GLP-1 receptor agonists/DPP-4 inhibitors: 982 patients; other antidiabetic treatment: 2769 patients). The adjusted IRR of the composite outcome was 0·52 (95% CI: 0·42-0·65) for patients exposed to GLP-1 receptor agonists/DPP-4 inhibitors compared with patients exposed to other antidiabetics.

Interpretation: In patients with IBD and type 2 diabetes, we observed a lower risk of adverse clinical events amongst patients treated with GLP-1 based therapies compared with treatment with other antidiabetics. These findings suggest that treatment with GLP-1 based therapies may improve the disease course of IBD.

Keywords: ATC, Anatomical Therapeutic Chemical; CD, Crohn's disease; Colitis ulcerative; Crohn's disease; DPP, dipeptidyl peptidase; Dipeptidyl peptidase-4 inhibitors; GLP, glucagon-like-peptide; Glucagon-like-peptide 1 receptor agonists; IBD, inflammatory bowel disease; ICD, International Classification of Diseases; IMID, immune-mediated inflammatory disease; IR, incidence rate; IRR, incidence rate ratios; PY, person-years; Pharmacoepidemiology; Prognosis; SGLT2, Sodium-glucose Cotransporter-2; TNF, tumour necrosis factor; UC, ulcerative colitis.