Introduction

Overweight and obesity present global health challenges, often managed through lifestyle changes and medications like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which can cause gastrointestinal (GI) adverse events. However, research on their effects in non-diabetic populations is lacking.

Aims & Methods

This review addresses this gap by examining the impact of GLP-1 RAs on GI adverse events in non-diabetic overweight or obese individuals. We systematically reviewed the literature by conducting a search using PubMed and EMBASE, adhering to predefined inclusion and exclusion criteria, to assess GI adverse events linked with GLP-1 RAs in non-diabetic overweight or obese populations. We conducted a dose response meta-analysis to evaluate each adverse event associated with different GLP-1 RAs. The quality of the included studies was appraised utilizing the Cochrane Collaboration's assessment tool.

Results

Our systematic review and meta-analysis encompassed thirty-eight articles, incorporating data from a total cohort of 32,882 individuals. Predominant GI adverse effects observed included nausea, vomiting, diarrhea, constipation, and abdominal pain. Across all evaluated GLP-1 RAs, a notable elevation in nausea risk was noted, with orforglipron exhibiting the highest risk, succeeded by exenatide, tirzepatide, semaglutide, and liraglutide. Moreover, liraglutide, orforglipron, semaglutide, and tirzepatide were associated with heightened vomiting risk, while cagrilinitide and exenatide displayed no significant increase. Exenatide, cagrilinitide, and orforglipron demonstrated no significant association with diarrhea risk. Conversely, semaglutide and liraglutide correlated with an elevated risk of constipation, while cagrilinitide and exenatide did not exhibit a significant increase. Notably, certain GLP-1 RAs were linked to a heightened risk of abdominal pain, with liraglutide, semaglutide, and tirzepatide displaying significant increases, whereas orforglipron showed no significant elevation in abdominal pain risk.

Conclusion

In conclusion, GLP-1 RAs are associated with an increased risk of GI adverse effects, including nausea, vomiting, diarrhea, constipation, and abdominal pain. Importantly, distinct GLP-1 RAs exhibited varying degrees of risk for these adverse effects, underscoring the importance of tailored risk assessment and management strategies in clinical practice.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Clinical Case Summary

Introduction: Mastocytosis is an uncommon hematopoietic neoplasm characterized by clonal proliferation of atypical mast cells. The clinical manifestations of mastocytosis are heterogeneous,ranging from limited cutanous involvement to aggressive disease with various levels of extra cutanous multi-organ involvement. Most cases of mastocytosis are indolent, usually cutanous or indolent systemic mastocytosis (SM). Aggressive SM is a rare and often fatal disease. Gastrointestinal involvement in aggressive SM presents with non specific symptoms and the final diagnosis depends on the pathology. Herein, we present a special case of colonic mastocytosis
Clinical case: We report a case of 66 years old female patient who presented with chronic abdominal pain not responding to treatment. On physical examination showed abnormal abdominal pigmentation and reported that skin biopsy previously revealed urticaria pigmentosa. Laboratory investigations were unremarkable. Colonscopy was planned and showed diffuse reddish mottling of cecum and ascending colon. Multiple biopsies were taken and histopathological examination revealed focal crypt architectural distortion. The lamina showed moderate inflammatory cellular infiltrate. These are formed of lymphocytes and plasma cells with excess eosinophils > 100/HPF. Esinophilic cryptitis is seen. Subtle population of scattered ovoid cells with rounded ovoid nuclei are seen. Slide stained for CD117 revealed positive reaction highlighting frequent mast cells. Moderate diffuse colitis with frequent mast cells and excess eosinophils > 100/HPF. Picture is suggestive of mastocytosis involving colon. The patient started imatinib and prednisone and long term follow up showed complete relieve of abdominal pain.

Introduction

Hemorrhoidal disease affects 2-7% of patients with inflammatory bowel disease (IBD) (1,2), but treatment recommendations are limited due to apparent higher morbidity in this subset of patients (3,4). Currently, there is limited data about hemorrhoidal disease treatment in IBD, there is even less information regarding non-surgical treatment.

Aims & Methods

The authors aim to evaluate the safety and efficacy of office-based procedures in hemorrhoidal disease in patients with IBD. This is a retrospective and Portuguese multicenter study (7 centers) that included patients with IBD who underwent office-based procedures for hemorrhoidal disease between July 2013 and July 2021. Data relating to IBD and hemorrhoidal disease were analyzed namely success, relapse, and complications. Success was defined as a significant improvement in symptoms after office-based procedures, without the need for additional treatment. Relapse was defined as a worsening of symptoms, requiring new office-based procedures/surgery.

Results

129 patients were included, 70% with ulcerative colitis; in Crohn's disease, 5.4% had a history of perianal disease. Only 62% of patients had endoscopic remission and 18% were on biologics. Regarding Goligher's classification, the majority had grade II (48%). 77 patients underwent rubber band ligation (RBL), 44 patients underwent polidocanol injection and 8 patients underwent both techniques, in a total of 304 procedures (median of 2(2) sessions/patient). The treatment was effective in 88% of patients, of which 14% relapsed, with an average follow-up time of 55.3±34.5 months. Of 304 procedures, 17 (5.6%) procedures were complicated, in a total of 16 patients (12.4%), 2 (0.65%) required invasive treatment, without cases of pelvic sepsis. Success, relapse, and complications were not associated with IBD (type, medication, or remission at the time of treatment) (p>0.05). Success was greater in patients with Goligher grades I and II (p=0.037). Complications were higher in patients undergoing RBL (p=0.030) and in patients with Goligher grade III (p=0.031).

Conclusion

This is the first study about office-based procedures for hemorrhoidal disease in IBD, showing similar efficacy to the general population, with a low rate of complications, and should therefore be recommended in these patients.

References

1. Eglinton TW, Barclay ML, Gearry RB, Frizelle FA. The spectrum of perianal Crohn's disease in a population-based cohort. Dis Colon Rectum. 2012 Jul;55(7):773-7.
2. Choi YS, Kim DS, Lee DH, Lee JB, Lee EJ, Lee SD, et al. Clinical Characteristics and Incidence of Perianal Diseases in Patients With Ulcerative Colitis. Ann Coloproctol. 2018 Jun;34(3):138-143.
3. Jeffery PJ, Parks AG, Ritchie JK. Treatment of haemorrhoids in patients with inflammatory bowel disease. Lancet. 1977 May 21;1(8021):1084-5.
4. D'Ugo S, Franceschilli L, Cadeddu F, Leccesi L, Blanco Gdel V, Calabrese E, et al. Medical and surgical treatment of haemorrhoids and anal fissure in Crohn's disease: a critical appraisal. BMC Gastroenterol. 2013 Mar 11;13:47

Introduction

Loop ileostomy has been reported to reduce the risk of leakage and reoperation in patients undergoing sphincter-preserving surgery. The structural and functional changes in the loop ileostomy may contribute to the development of ileus, such as decreased motility of smooth muscle and villous atrophy.

Aims & Methods

This study is to investigate the morphological, functional, and molecular changes of the distal limb after ileostomy and subsequent takedown.
Human ileum samples were obtained from patients who underwent diversion ileostomy after rectal cancer surgery and subsequently had ileostomy takedown. Samples were collected from the tips of the proximal and distal limbs. The whole layer of ileum was prepared for HE staining and the muscle layer which the mucosal layer was removed was prepared for motility measurement. The muscle strips (5x2 mm) were mounted to an isometric force transducer (Biopac Systems, Inc., Goleta, CA, USA) and suspended in 10 ml organ bath containing aerated (97% O₂ and 3% CO₂) and pre-warmed (36.5 ± 0.5°C) KRB solution. Amplitude (mN) and area under the curve (AUC) of contractions were measured and analyzed. To compare myogenic contraction and relaxation between the proximal and distal limbs of ileostomy, we administrated acetylcholine (ACh), potassium chloride (KCl) and sodium nitroprusside (SNP) in human ileal strips. Quantitative real-time polymerase chain reaction (qPCR) was performed for quantitative analysis of the expression of VAChT and NOS, cholinergic and nitrergic neuronal markers, and UCHL1 and MYH11, neuronal and smooth muscle cell marker, respectively.

Results

The height of the villi and the thickness of the mucosa, submucosa and muscle layer of the distal limb decreased significantly compared to those of the proximal limb. In the contractile responses to ACh and KCl, the amplitude and AUC of contractions in the distal limb were smaller than in the proximal limb in a dose-dependent manner. The relaxation response to the SNP in the distal limb was reduced compared to the proximal limb. Expressions of VAChT which is related with cholinergic neurotransmission, UCHL1 and MYH11 were not different in both proximal and distal limbs. However, expression of NOS1 which is related with nitrergic neurotransmission was increased significantly in the distal limb compared to the proximal limb. In addition, number of interstitial cells (ICC and PDGFRa⁺ cell) in muscle layer was not different in both proximal and distal limbs.

Conclusion

These results demonstrate that the distal limb which was not in use for a certain period of time after fecal diversion was morphologically atrophied and its motility was also impaired. Both myogenic contractile and relaxation responses were reduced in the distal limb of ileostomy although nitrergic neurons increased in the distal limb to compensate for the reduced relaxation response. These findings suggest that stimulating the distal limb can induce relaxation and may be a way to prevent ileus, which can occur after ileostomy takedown.