- Previous research has suggested that GLP-1 receptor agonists may offer benefits in inflammatory bowel disease.
- In a retrospective cohort study of patients with ulcerative colitis, use of liraglutide or semaglutide was associated with higher remission rates compared with no use at 12 weeks.
- Weight loss was not independently associated with remission.
The use of GLP-1 receptor agonists was linked to improved remission rates in patients with ulcerative colitis, a retrospective cohort study suggested.
Among 300 patients with ulcerative colitis, use of liraglutide (Victoza, Saxenda) or semaglutide (Ozempic, Wegovy) for metabolic indications was associated with higher remission rates compared with no use at 4 weeks (34.7% vs 15.3%, P=0.001), 8 weeks (54.7% vs 18%, P<0.001), and 12 weeks (66.7% vs 25.3%, P<0.001), reported Budoor Alqinai, MBChB, MSc, of West Virginia University in Morgantown, and colleagues.
After adjusting for age, sex, baseline partial Mayo score, obesity, diabetes status, and category of concomitant biologic therapy, the use of GLP-1 drugs was strongly and independently associated with symptomatic remission (adjusted OR 5.90, 95% CI 3.52-9.86, P<0.001), they noted in Inflammatory Bowel Diseases.
When broken down by the type of GLP-1 drug used, there was a modest advantage with semaglutide versus liraglutide, with symptomatic remission rates of 72.5% and 60% at 12 weeks, respectively (OR 1.77, 95% CI 1.02-3.25, P=0.04).
"Notably, clinical improvement preceded meaningful weight loss, supporting a potential weight-independent anti-inflammatory mechanism," Alqinai and team wrote.
"These real-world findings support a potential adjunctive role" for GLP-1 receptor agonists in ulcerative colitis, though confirmation in prospective studies, including randomized controlled trials, is needed, they added.
These findings build upon those from previous research suggesting that GLP-1 agonists may offer benefits in inflammatory bowel disease (IBD) that extend beyond their metabolic indication.
For example, a recent real-world study showed that the use of GLP-1 drugs was associated with significantly lower rates of corticosteroid dependence and fewer hospitalizations among adults with overweight/obesity and Crohn's disease. In addition, a large database study found that GLP-1 drug use was linked to improved outcomes across multiple clinical endpoints in patients with ulcerative colitis and Crohn's.
According to preclinical studies, "GLP-1 signaling reduces pro-inflammatory cytokine production, enhances epithelial barrier function, and attenuates colonic inflammation in experimental models of IBD," Alqinai and team explained. Moreover, "GLP-1 receptor activation has been shown to promote mucosal healing through modulation of immune pathways and improvement in intestinal permeability."
For this study, the researchers used electronic health record data from the West Virginia University health system from 2022 to 2024 and included 300 patients with ulcerative colitis -- 150 who received either liraglutide (46.7%) or semaglutide (53.3%) during the study period and a control cohort of 150 patients who did not receive a GLP-1 drug.
Mean age was similar between groups (46 vs 47 years, respectively), and most patients were women. Patients were mostly overweight or obese, with approximately 80% of patients in each group having a body mass index of 30 or higher. Type 2 diabetes was present in 35% of GLP-1 drug users and 34% of controls.
The primary outcome was symptomatic remission at 12 weeks (defined as a partial Mayo score ≤2, with a rectal bleeding subscore of 0, which indicated minimal to no symptoms and no visible blood in stool).
Mean partial Mayo scores improved from 5.8 at baseline to 2.1 at 12 weeks in the GLP-1 receptor agonist group versus an improvement of 5.7 to 4.6 in controls (P<0.001 for between-group comparison).
An exploratory analysis of a subset of patients who underwent follow-up endoscopy within a 10- to 14-week window showed that endoscopic remission (Mayo Endoscopic Subscore [MES] ≤1) was achieved in 58% of GLP-1 drug users compared with 38% of controls. Endoscopic improvement (≥1-point reduction in MES from baseline) was seen in 69% and 47%, respectively.
In the GLP-1 drug group, mean weight loss was 8.2% at 12 weeks, which Alqinai and team noted was consistent with the expected effect. However, a multivariable analysis adjusting for age, sex, baseline disease activity, obesity, and diabetes status showed that weight loss was not independently associated with remission (adjusted OR 1.03 per 1% weight loss, 95% CI 0.95-1.12, P=0.41).
GLP-1 drugs were generally well tolerated, with common, but mostly mild, gastrointestinal side effects. Approximately 30% of patients reported transient nausea in the first few weeks of therapy, and 10% reported occasional vomiting.
There were no drug discontinuations due to side effects during the 12-week observation period, and no IBD-specific adverse events were attributed to GLP-1 drug use.
The authors acknowledged that the study was limited by its retrospective design, and pointed out that despite 1:1 matching on key prognostic variables and multivariable adjustment, residual confounding could not be entirely eliminated.
Disclosures
The authors reported no conflicts of interest.
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