Introduction
The global prevalence of inflammatory bowel disease (IBD) and type 2 diabetes mellitus (DM2) is on the rise. Previous studies suggest an increased risk of DM2 in IBD patients[1], while some have demonstrated an association between specific anti-diabetic drugs and IBD incidence and outcomes[2,3]. This study aims to evaluate the longitudinal association of a wide range of anti-diabetic treatments and IBD outcomes in a big national registry.
Aims & Methods
We analyzed data from the epi-IIRN, a nationwide cohort of all IBD patients in Israel. Our study population consisted of patients with both IBD and DM2. DM2 patients were identified if they had at least two instances of either any DM2 international classification of diseases 9 diagnoses, or a purchase of a non-insulin anti-diabetic medication. Patients were followed from their initial diagnosis of both IBD and DM2 until death or the end of the cohort (September 2021). The primary outcome was IBD treatment escalation defined as new treatment with systemic steroids, initiation/substitution of biologic therapy, or an IBD-related hospitalization or surgical procedure. Primary exposure variables were anti-diabetic treatment (grouped by mechanism of action), and covariates included age, IBD subtype, previous surgeries, perianal disease, body mass index (BMI), use of immunomodulators, hemoglobin and HbA1C values. Missing numeric values were completed from a previously recorded value for the same patient under a carry forward assumption. Due to the high proportion of older patients with multiple comorbidities, analysis was performed using survival analysis with a subdistribution function for competing risks of death.
Results
3,675 patients with both IBD (50.6% ulcerative colitis) and diabetes were included. The median age at the beginning of follow-up was 59 years (interquartile range [IQR] of 18), with a median follow-up of 6.2 years (IQR of 7.4). The most common anti-inflammatory drug at the beginning of follow-up was 5-ASA [2,046 patients (55.7%)], followed by systemic steroids and thiopurines (12.9% and 5.9%, respectively). The most common anti-diabetic drug at the beginning of follow-up was metformin [1,929 patients (52.5%)], followed by insulin and dipeptidyl-peptidase 4 inhibitors (DPP4-I) (11.6% and 10.2%, respectively). The median glycated hemoglobin value was 6.7% (IQR 1.5).
There were 161 treatment escalation events per 1,000 patient-years, and 497 patients (13.5%) died during follow-up. A multivariable competing risks analysis revealed that newer anti-diabetic treatments, including DPP4-I, glucagon-like peptide-1 agonists, sodium-glucose co-transporter-2 inhibitors, were associated with a reduced adjusted risk of treatment escalation (adjusted hazard ratios [aHR] and 95% confidence intervals [CI] of 0.73 [0.68, 0.79], 0.74 [0.66, 0.83], and, 0.77 [0.70, 0.85], respectively). However, this association was not observed for metformin or sulfonylureas. Insulin was associated with a slightly increased risk of treatment escalation (aHR and 95% CI of 1.10 [1.04, 1.18]).
Conclusion
The use of newer anti-diabetic drugs, but not older anti-diabetics, was associated with favorable outcomes in patients with both IBD and DM2. Further research is warranted to study the individual effects of various anti-diabetics on treatment outcomes of various anti-inflammatory therapies in IBD.
References
Patients: A Nationwide Population-Based Study in Korea. J Clin Med 2019, Vol 8, Page 343 2019;8:343. doi:10.3390/JCM8030343
2 Abrahami D, Douros A, Yin H, et al. Dipeptidyl peptidase-4 inhibitors and incidence of inflammatory bowel disease among patients with type 2 diabetes: population based cohort study. BMJ 2018;360:872. doi:10.1136/BMJ.K872
3 Villumsen M, Schelde AB, Jimenez-Solem E, et al. GLP-1 based therapies and disease course of inflammatory bowel disease. eClinicalMedicine 2021;37. doi:10.1016/j.eclinm.2021.100979
4 Friedman MY, Leventer-Roberts M, Rosenblum J, et al. Development and validation of novel algorithms to identify patients with inflammatory bowel diseases in Israel: an epi-IIRN group study. Clin Epidemiol 2018;10:671–81. doi:10.2147/CLEP.S151339
