Acute ischaemic colitis after initiation of tirzepatide in an elderly patient with type 2 diabetes

Use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists is increasing among reproductive-aged women for obesity, diabetes, polycystic ovary syndrome (PCOS), and cardiometabolic disease. However, the safety of these agents in pregnancy and lactation remains sparse, while inadvertent first-trimester exposure is becoming more common. The aim of this review is to systematically evaluate maternal, fetal, neonatal, and lactation outcomes following preconception, in-pregnancy, or postpartum exposure to GLP-1 and dual GLP-1/GIP receptor agonists. We conducted a systematic review of PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library from inception to 23 September 2025. Human studies reporting exposure to GLP-1 or dual GLP-1/GIP receptor agonists during preconception, pregnancy, or lactation were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using validated tools. Given clinical heterogeneity, findings were synthesised narratively in accordance with PRISMA 2020 guidelines. Thirty-six studies met the inclusion criteria. Across large observational cohorts, periconceptional or early-pregnancy exposure to GLP-1-based therapies was not consistently associated with increased risk of major congenital malformations in adjusted analyses, fetal growth restriction, stillbirth, or neonatal mortality compared with insulin-treated or disease-matched controls. Maternal outcomes, including gestational diabetes, hypertensive disorders of pregnancy, preterm birth, and gestational weight gain, were heterogeneous without a reproducible safety signal. Indeed, in women with PCOS, GLP-1RAs seem promising in various aspects. Lactation data were sparse; one pharmacokinetic study reported no detectable semaglutide transfer into human milk. Current evidence suggests that preconceptional or early-pregnancy exposure to GLP-1-based therapies is not consistently associated with increased maternal, fetal, or neonatal risk, although data on continued use throughout gestation remain limited.

The purpose of this review is to highlight the role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (GLP-1/GIP RAs) in managing cardiovascular-kidney-metabolic (CKM) syndrome, focusing on their cardiovascular (CV) and kidney-protective effects beyond glycemic control. In multiple randomized controlled trials, GLP-1 RAs were demonstrated to confer significant benefits in reducing CV events and preserving kidney function in patients with preexisting atherosclerotic cardiovascular disease (ASCVD) and those at high CV risk. Current guidelines, including those from the Kidney Disease: Improving Global Outcomes (KDIGO) initiative and the American Diabetes Association (ADA), underscore the therapeutic potential of these agents for managing chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and metabolic syndrome. Additionally, emerging data suggests their utility beyond T2DM. This review summarizes the evidence supporting these guidelines, along with newer findings not yet fully integrated into clinical practice. It also examines the role of pharmacists and multidisciplinary teams, safety considerations, and practical strategies for managing common adverse effects. The integration of GLP-1 RAs and dual GLP-1/GIP RAs into clinical practice offers substantial benefits for patients, both with and without diabetes. Pharmacists play a pivotal role in recommending evidence-based treatments for those at high CV and kidney risk, educating patients, addressing social determinants of health, and bridging gaps across multidisciplinary care teams.

Ischemic colitis: Who will survive?

A Review of Incretin Therapies Approved and in Late-Stage Development for Overweight and Obesity Management

208-OR: Comparable Improvement in NAFLD, Weight Loss, and Lipid Metabolism in Rats Treated with Dual GLP-1–GIP Receptor Agonist (Tirzepatide) and Gastric Sleeve

In the management of hypertension, only limited advances have been made over the past decades. Recent studies highlight the potential of next-generation incretin-based therapeutics, such as GLP-1 RAs (glucagon-like peptide-1 receptor agonists) like semaglutide and dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonists like tirzepatide. These drugs not only promote weight loss but also substantially lower blood pressure (BP) and reduce cardiovascular end points. The extent to which incretin-based therapies improve disease outcomes via weight loss versus so-called direct tissue effects is the subject of great interest, not only for BP but also for other clinical outcomes. Although, incretin-based therapeutics were initially not designed to treat hypertension, clinical studies demonstrate an impressive reduction in BP in patients treated with these agents, with an even more pronounced effect in patients with obesity and hypertension. The current hypertension guidelines must address the robust evidence supporting the use of incretin-based therapeutics in patients with hypertension. A caveat is that no trial to date has used BP reduction as the primary end point when investigating the interaction between GLP-1 or GLP-1/GIP receptor agonists and antihypertensive medications. However, in patients with type 2 diabetes or a body mass index >27 kg/m2, these drugs are widely used and lower BP. Taken together, incretin-based therapeutics represent a promising therapeutic tool to improve both BP and cardiovascular outcomes and help evolve the landscape of hypertension treatment.

58-OR: The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Transiently Delays Gastric Emptying Similarly to a Selective Long-Acting GLP-1 Receptor Agonist

Introduction/Objective Inflammatory bowel disease (IBD) and acute ischemic colitis can both be involved by active colitis. IBD is characterized by crypt architectural distortion, basal lymphoplasmacytosis, and occasional granulomatous changes. However, diagnosis of IBDs is still largely by exclusion of other types of active colitis with similar changes. We previously demonstrated that glucose regulated protein 94 (grp94) is mainly expressed by activated plasma cells. We postulate that increased numbers of grp94-positive plasma cells may support diagnosis of IBDs. Here, we compared IBD and active ischemic colitis for grp94 expression in mucosal plasma cells of colectomy specimens Methods/Case Report Tissue sections from colectomy specimens with active IBD (n = 8) and ischemic colitis (n = 7) were examined for grp94 expression by immunohistochemistry (monoclonal antibody clone 9G10 at dilution of 1:200, Enzo Life Science, Inc Farmindale, NY). The staining intensity and highest number of grp94 in plasma cells per high power field was counted and recorded for each case, and combined scores were calculated as # of plasma cells multiplied by staining intensity (ranging from 0 to 3+). Unpaired student T tests were used to compare these indices between the two groups for statistical significance (p value < 0.05 was considered significantly different) Results (if a Case Study enter NA) Plasma cells in lamina propria identified by grp94 staining showed higher intensity in IBD than ischemic groups. The number of plasma cells and combined scores were also significantly higher in the IBC group than that of ischemic group Conclusion Our data indicates that active plasma cells are much more numerous in IBD than ischemic colitis, supporting the notion that active plasma cells are involved in the development of this disease process. Morphologically, active colitis with increased number of plasma cells appears to be another index favoring the diagnosis of IBD.

Ischemic Colitis (IC) is a common cause of intestinal tract ischemic injury and is caused by transient hypoperfusion to the gut. Ischemic colitis is associated with female and elderly patients but can occur in younger patients with a precipitating cause. Contributors include vascular abnormalities, coagulation disorders and medications, including oral contraceptives and antibiotics. Typical presentation includes sudden onset cramping lower abdominal pain and bright red blood per rectum with blood clots. Endoscopic evaluation and histology is the gold standard to diagnose colon ischemia, but this may be time consuming and invasive. Our patient is a 24-year old woman with abdominal pain and bloody diarrhea. She was in her normal state of health until experiencing two days of sudden onset left sided abdominal pain, cramping, tenesmus and multiple episodes of bloody diarrhea. She denied fevers or chills, weight loss, foreign travel, abnormal food intake or family history of IBD. She later endorsed intermittent hematochezia for the past two years. Medications included chronic combined estrogen-progesterone oral contraceptive and new medication of doxycycline po bid this year. She had no previous endoscopies. Labs were notable for leukocytosis, negative pregnancy test, positive fecal leukocytes and CT scan w/o contrast indicating a nonspecific colitis in the sigmoid and descending colon. The patient was given empiric antibiotics and supportive care with initial resolution of leukocytosis and symptom improvement. Stool studies were negative and antibiotics were discontinued, but recurrence of bloody diarrhea and blood clots in her stool prompted further workup. Sigmoidoscopy was performed showing ishemic colitis, confirmed on pathology. Patients may undergo unnecessary treatment and testing for other pathologies such as infection, IBD or malignancy. Our patient improved with conservative management but surgery may be required in cases of gangrene colitis or stricture. Associations between ocp, antibiotics and acute ischemic colitis have been described previously. Our patient endorsed intermittent hematochezia prior to starting doxycycline, suggesting chronic colonic ischemia due to ocp prior to developing acute ischemic colitis from doxycycline sensitivity. Our case illustrates the need for a high index of suspicion for IC in young patients and further research is needed to determine potential synergistic mechanisms of medications that may cause ischemic colitis.1595_A Figure 1. Images from the sigmoid colon showing loss of vascularity and as well as erythema and edema consistent with ischemic colitis.1595_B Figure 2. Images from the sigmoid colon showing loss of vascularity and as well as erythema and edema consistent with ischemic colitis.1595_C Figure 3. Demonstration of colonic mucosa with mucosal hemorrhage and detachment of surface epithelial cells from the basement membrane. Necrosis of the superficial crypts with hyalinization of the lamina propria is noted. Findings are consistent with acute ischemic colitis.

Purpose: Acute ischemic colitis (IC) is a life-threatening abdominal disease that requires early diagnosis and therapy to prevent bowel necrosis and ultimately patient's death. It is unknown whether the patient's status and background with regard to prior hospitalization may have an impact on the therapeutic management and clinical course. Aim of this study was to examine whether the patient's background may influence the surgical treatment and outcome of patients with IC. Methods: All patients with IC who received surgical treatment at our institution from January 2002 to January 2008 were prospectively included in a database. For further analysis, we subdivided all patients into the two groups “in-hospital patients” (G1) and “out-hospital patients” (G2). Results: Of the 177 patients (113 men, 64 women) with IC, 121 were assigned to G1 and 56 to G2. Low cardiac output was the predominant cause for development of IC in G1 (64.5% in G1 vs. 23.2% in G2) while occlusion of the mesenteric artery (32.1% in G1 vs. 15.7% in G2) was more prevalent in G2. Surgical therapy consisted of subtotal colectomy (predominantly performed in G1) and right or left hemicolectomy (mainly performed in G2). Overall morbidity and mortality (52.1% vs. 39.3%; p = 0.1) was increased in the in-hospital patient group, though this difference was not statistically significant. Conclusion: The present study for the first time indicated that the hospital status of patients diagnosed with IC substantially influences surgical treatment and clinical outcome. These observations might help to facilitate adequate clinical management and surgical therapy of patients with IC.

Background: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) usually coexist and are related to increased morbidity and mortality. Cardiovascular benefits have been demonstrated by drugs such as sodium-glucose cotransporter-2 inhibitors (SGLT2i) and GLP-1 receptor agonists including the dual GIP/GLP-1 receptor agonist tirzepatide (collectively, incretin-based therapies); however, their relative effectiveness in patients with concomitant AF and HFpEF remains undefined. Methods: We conducted a retrospective, propensity score-matched cohort study utilizing the TriNetX Global Collaborative Network. Adults with AF or atrial flutter with a diagnosis of HFpEF who initiated incretin-based therapies (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) or SGLT2i were included; index medication was required to be initiated within 30 days of a qualifying AF/HFpEF diagnosis. 1:1 matching was performed based on baseline medications, demographics, and comorbidities. Co-primary outcomes were all-cause mortality, inpatient visits, and emergency department (ED) visits at 1 year. Secondary outcomes included myocardial infarction, ischemic stroke, acute kidney injury, transient ischemic attack, major adverse cardiovascular events (MACE; all-cause mortality/MI/stroke composite), and AF-related procedures. Agent-specific subgroup analyses were performed for semaglutide and tirzepatide separately. Sensitivity analyses were conducted at 6 months and 2 years. Results: 7624 patients were included in each cohort after matching (mean age: 70.8 years; 52% women). At 1 year, incretin-based therapy was associated with lower all-cause mortality (5.3% vs. 7.3%, HR 0.721, 95% CI 0.634–0.820; p < 0.001), fewer inpatient visits (30.0% vs. 37.4%, HR 0.743, 95% CI 0.702–0.787; p < 0.001), and no statistically significant difference in ED visits (27.0% vs. 28.0%; HR 0.946, 95% CI 0.888–1.007; p = 0.081) compared with SGLT2i. Incretin-based therapy was also associated with lower risk of MACE (HR 0.709), acute kidney injury (HR 0.751), myocardial infarction (HR 0.583), catheter ablation (HR 0.685), and electrical cardioversion (HR 0.472). No significant differences were observed in ischemic stroke or transient ischemic attack. These findings were broadly consistent at 6-month and 2-year follow-up, and directionally consistent in agent-specific subgroup analyses of semaglutide and tirzepatide. Conclusions: In this large propensity-matched cohort of patients with AF and HFpEF, initiation of incretin-based therapy (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) was associated with lower all-cause mortality, fewer inpatient visits, and reduced cardiovascular events compared with SGLT2i. These findings, while subject to observational limitations, suggest potential benefits of incretin-based therapy in this high-risk population and support the need for prospective comparative trials.

Colonic ischemia is the most common form of intestinal ischemia and is defined by the reduction of blood flow to a level insufficient to maintain cellular metabolic function. Rheumatoid vasculitis (RV) can occur in up to 5% of rheumatoid arthritis (RA) patients with intestinal involvement in 10-38% of patients. We report a rare case of RA as the cause of isolated right sided colonic ischemia. A 61-year-old African American woman with a history of RA, pulmonary sarcoidosis, and hypertension presented with abdominal pain and non-bloody diarrhea for two weeks. She reported four to five loose watery bowel movements a day. The abdominal pain was intermittent, cramping, and not associated with food. She also endorsed joint stiffness in her hands. Her medication list included daily aspirin 81mg, hydroxychloroquine 400mg, prednisone 5mg, hydrochlorothiazide 25mg, and twice daily leflunomide 20mg. She was previously on etanercept and stopped 6 months prior.Significant physical exam findings revealed a normotensive patient with mild diffuse abdominal tenderness, metacarpophalangeal joint swelling, and swan neck deformity of her fingers. Other than high titers of rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody, and elevated c-reactive protein (1.7mg/dL), laboratory workup was unremarkable with a negative infectious workup. Colonoscopy revealed multiple superficial linear ulcerations with erythematous borders from the cecum to the hepatic flexure. Pathology from the biopsies showed no granulomas but noted areas of hemorrhage, ischemia, and nuclear dust suggestive of neutrophilic vasculitis surrounding thrombosed small vessels consistent with RV. A CT angiography showed diffuse mucosal enhancement of the ascending colon with associated fat stranding and patent abdominal arterial vasculature. Her symptoms resolved after supportive treatment, titration of prednisone, and restarting etanercept. Clinicians should be aware of RA as a rare cause of colonic ischemia. Although there are no formal diagnostic criteria, the diagnosis should be suspected in patients with colonic ischemia who have RA, high titers of RF with characteristic histopathology showing neutrophilic vasculitis on colonoscopy biopsies after more common causes are ruled out. The pathogenesis is thought to arise from immune complex formation from RF in small vessels. Treatment involves supportive care and immunosuppression of the RA.1556_A Figure 1. Colonoscopy showing superficial ulcerations in the right colon.1556_B Figure 2. Abdominal CT showing mucosal enhancement of the ascending colon.1556_C Figure 3. Histopathology showing nuclear dust suggestive of neutorphilic vasculitis surrounding a thrombotic small vessel.

Ischemic colitis (IC) is a rare adverse effect of antipsychotic medications and is most commonly associated with the phenothiazine class of neuroleptics. Different cases reported in patients without other obvious risk factors led to the link between taking neuroleptics and acute ischemic colitis. The severe form is acute necrotizing colitis. This entity is characterized by sudden onset of abdominal pain and bloody diarrhea, progressing rapidly to produce severe illness with general peritonitis and shock.We report a case of a 26 years old Moroccan man, treated for four years for chronic psychosis, admitted to the emergency for abdominal pain and diarrhea. Clinical examination showed a conscious patient, tachycardia at 120 beats/min, febrile to 38.5 ° C, with generalized abdominal defense. Laboratory tests revealed: GB 33400, CRP 290 mg/l, abdominal tomography revealed colonic distension. The patient was prepared and admitted to the operating room. During the intervention, a colonoscopy was performed and shown ulcerated lesions with a purplish background without interval healthy mucosa. A subtotal colectomy with ileostomy and sigmoidostomy were performed. The histological examination of the surgical specimen showed superficial and extended ulcerations without interval healthy mucosa. Thus, no factors for IC were detected by appropriate workup other than the long-time use of neuroleptics. The restoration of continuity by ileorectal anastomosis was achieved two months later with a good clinical outcome, and the patient was recommended for psychiatry to reevaluate his antipsychotic regimen given the association with IC.Our case supports that neuroleptics can promote IC in patients under antipsychotic medications. It should alert physicians who prescribe neuroleptics and colorectal surgeons to the possibility of intestinal ischemia. Although the clinical presentation is non-specific, abdominal pain and distension should be headed, and endoscopy carried out. A better knowledge of this condition should promote earlier diagnosis and improve management.

A Clostridioides difficile infection (CDI) is one of the major nosocomial diarrheal diseases. Pseudomembranous colitis (PMC) is a characteristic endoscopic finding of CDI, manifested by white or yellowish plaque covering the colonic mucosa. Ischemic colitis is inflammation of the colon manifested by mucosal denudation and friability. Ischemic colitis is rarely associated with CDI. The treatment response might be delayed when CDI is complicated with other diseases that cause diarrhea. Thus far, reports of CDI concomitant with Cytomegalovirus (CMV) colitis are rare. This paper reports a case of PMC and ischemic colitis associated with CDI and CMV infection. After two weeks of oral vancomycin and intravenous metronidazole, the patient's diarrhea was not improved. Follow-up sigmoidoscopy was performed, and a CMV infection was identified at areas of broad ulceration where ischemic colitis occurred. Finally, the patient was cured with ganciclovir. Follow-up sigmoidoscopy showed an improvement in ischemic colitis.

849-P: Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of an Optimized Dual GLP-1/GIP Receptor Agonist (BGM0504) in Healthy Subjects—A Phase Ia, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study