Pancreatitis

New Study Links GLP-1 Agonists to Serious GI AEs

Posted by

0


Popular glucagon-like peptide-1 receptor agonists are associated with serious gastrointestinal adverse effects such as pancreatitis, gastroparesis and bowel obstruction, according to the results of a large retrospective study.

These agents “have potential serious side effects, and prescribers should be aware of them and feel comfortable managing adverse events [AEs] and understanding appropriate dosing strategies,” said Eduardo Grunvald, MD, the director of the weight management program at the University of California, San Diego, and lead author of the 2022 American Gastroenterological Association guidelines on drug therapy for obesity, who was not involved in the research.

In the study, researchers at the University of British Columbia evaluated patients prescribed the GLP-1 agonists semaglutide (Ozempic/Wegovy, Novo Nordisk) and liraglutide (Victoza/Saxenda, Novo Nordisk) for weight loss, comparing their effects with those of naltrexone-bupropion (Contrave, Currax), a weight-loss agent with a different mechanism of action.

The researchers used a random sample of 16 million patients from the PharMetrics Plus database between 2006 and 2020, a timeframe that covers the FDA approvals for weight-loss indication with liraglutide in 2014 and semaglutide in 2021. They ensured every case had an obesity code in the 90 days before or up to 30 days after entry into the study. Patients with a diabetes diagnosis or an antidiabetic drug code were excluded.

image

The results, published in JAMA (2023 Oct 5. doi:10.1001/jama.2023.19574), suggested that use of semaglutide and liraglutide for weight loss is associated with an increased risk for pancreatitis (adjusted hazard ratio [aHR], 9.09; 95% CI, 1.25-66.00), gastroparesis (aHR, 3.67; 95% CI, 1.15-11.90) and bowel obstruction (aHR, 4.22; 95% CI, 1.02-17.40) compared with naltrexone-bupropion. The incidence of pancreatitis per 1,000 patients was higher for both GLP-1 agonists relative to naltrexone-bupropion (semaglutide, 4.6 per 1,000; liraglutide, 7.9 per 1,000; and naltrexone-bupropion, 1.0 per 1,000). The incidence of gastroparesis—an AE that could not only cause nausea and vomiting, among other symptoms, but also could affect endoscopic procedures (see box)—was also higher for the GLP-1 agonists (semaglutide, 9.1/1,000; liraglutide, 7.3/1,000; and naltrexone-bupropion, 3.1/1,000). The incidence of bowel obstruction was higher in patients on liraglutide (8.1/1,000) than semaglutide (zero) or naltrexone-bupropion (1.7/1,000).

AGA Says Don’t Unilaterally Stop GLP-1 Agonists Before Endoscopy

Before endoscopy, clinicians should review the effects of glucagon-like peptide-1 receptor agonist medications on a patient-by-patient basis and not unilaterally stop GLP-1 agonist medications due to their links to GI adverse events, according to a new clinical practice update from the American Gastroenterological Association (Clin Gasterol Hepatol 2023 Nov 7. doi:10.1016/j.cgh.2023.11.002).

The clinical practice update follows accumulating research that GLP-1 agonist drugs used for weight loss are linked to GI side effects such as delayed gastric emptying and gastroparesis in certain patients. Anesthesiologists have reported instances of incomplete gastric emptying after fasting in patients taking semaglutide, and the American Society of Anesthesiologists (ASA) released guidance in June 2023 recommending that these medications be held before elective surgeries (see related commentary).

However, the AGA guideline authors stressed that stopping these agents before endoscopic procedures should be individualized based on the patient’s current symptoms. “While GLP-1 [receptor agonists] might slow gastric emptying in some patients, there is overall insufficient evidence for ‘blanket statements’ on how to manage patients taking these medications who require endoscopy,” noted Andrew Wang, MD, the director of interventional endoscopy at the University of Virginia, in Charlottesville, who co-authored the new AGA guidance, in an AGA press release.

Dr. Wang and his co-authors recommend that endoscopists proceed with planned endoscopies in patients on GLP-1 agonists who have followed standard fasting instructions and who do not have nausea, vomiting, dyspepsia or abdominal distension. Instead of stopping medications, they recommend that some patients can be put on a liquid` diet the day before an endoscopy. If patients have symptoms that suggest retained gastric contents but providers cannot delay an endoscopic procedure, they recommended that gastroenterologists consider rapid sequence intubation, although they noted this may not be an available option in ambulatory or office-based procedure settings.

Philip Schoenfeld, MD, MSEd, MSc (Epi), and Sonali Paul, MD, MS, reviewed a recent JAMA study on GLP-1 agent side effects (see main story) in in the November 15 issue of Evidence-Based GI and discussed the study and the issues related to holding GLP-1 agents for endoscopic procedures in an accompanying audio summary.

Pointing to differing stances the ASA and GI societies have taken, Dr. Paul, an assistant professor of medicine at the University of Chicago School of Medicine, said, “I know the anesthesia guidelines came out and said that we should be holding these meds and I know our own GI societies came out and said there isn’t enough evidence right now.” But, she added, at her institution, the anesthesiologists “said they won’t actually perform anesthesia for our procedures if a patient is on a GLP-1. For someone is on daily GLP-1, they recommend holding it the day of and the day before and for the folks who are on it weekly, they should be held the week before.” Given the need to work with anesthesiologists on many of these cases, she said, “at this point, we are going with what our anesthesia colleagues tell us.”

Dr. Schoenfeld, the chief (emeritus) of the Gastroenterology Section at the John D. Dingell VA Medical Center, in Detroit, agreed, saying “If you’re going to do propofol with your anesthesia colleagues, and their guidelines say that [these drugs need to be held], then you have to comply with that.” However, he said, “based on what our own GI societies have said, if I’m doing a colonoscopy on somebody who’s on semaglutide and they haven’t held it for a week, I still feel comfortable going ahead and just using [midazolam] and fentanyl in an open endoscopy setting for those patients.” But, he added, “That’s something each endoscopist will have to decide for themself.”

—Meaghan Lee Callaghan and Sarah Tilyou

The incidence of biliary disease per 1,000 patients was similar in all groups, although slightly higher in those taking liraglutide (semaglutide, 11.7/1,000; liraglutide, 18.6/1,000; and naltrexone-bupropion, 12.6/1,000).

The researchers noted that a main limitation was the study’s observational nature, and while they included only GLP-1 agonist users with a record of obesity, they indicated it is uncertain whether GLP-1 agonists were used specifically for weight loss in each case.

Underscoring the implications of these potential AEs, Dr. Grunvald said “these adverse events are rare, but given the potential number of people that will use them, absolute numbers of serious adverse events will not be trivial.” Nevertheless, he added, “I also strongly believe, based on emerging data and my own clinical experience, the overall benefits outweigh these risks in general.”

In an audio summary discussion in the November 15 issue of Evidence-Based GI, Sonali Paul, MD, MS, an assistant professor of medicine at the Center for Liver Diseases at the University of Chicago School of Medicine, also pointed to the importance of these potential AEs because of the growing use of the GLP-1 agents. She noted that some of the GI side effects of these drugs, such as nausea, often can be mitigated with dosing strategies and other methods. But she expressed concern about the finding related to pancreatitis. “The pancreatitis signal is definitely real,” she said. “If I have a patient that is on a GLP-1 and develops pancreatitis, I think for me, and for most of my endocrine colleagues, that’s a case where we stop the GLP-1 and we don’t rechallenge.”

Issues in hypertriglyceridemic pancreatitis: an update..

Posted by

0


Abstract

Hypertriglyceridemia (HTG) is a well-established but underestimated cause of acute pancreatitis and recurrent acute pancreatitis. The clinical presentation of HTG-induced pancreatitis (HTG pancreatitis) is similar to other causes. Pancreatitis secondary to HTG is typically seen in the presence of one or more secondary factors (uncontrolled diabetes, alcoholism, medications, pregnancy) in a patient with an underlying common genetic abnormality of lipoprotein metabolism (familial combined hyperlipidemia or familial HTG). Less commonly, a patient with rare genetic abnormality (familial chylomicronemic syndrome) with or without an additional secondary factor is encountered. The risk of acute pancreatitis in patients with serum triglycerides >1000 and >2000 mg/dL is ∼5% and 10% to 20%, respectively. It is not clear whether HTG pancreatitis is more severe than when it is due to other causes. Clinical management of HTG pancreatitis is similar to that of other causes. Insulin infusion in diabetic patients with HTG can rapidly reduce triglyceride (TG) levels. Use of apheresis is still experimental and better designed studies are needed to clarify its role in the management of HTG pancreatitis. Diet, lifestyle changes, and control of secondary factors are key to the treatment, and medications are useful adjuncts to the long-term management of TG levels. Control of TG levels to 500 mg/dL or less can effectively prevent recurrences of pancreatitis.

Source: PMID

 

 

 

 

Plasmapheresis as a therapeutic approach for hypertriglyceridemia-induced acute pancreatitis.

Posted by

0


Abstract

Acute pancreatitis is an inflammatory condition that is clinically manifested by abdominal pain and elevated serum levels of pancreatic enzymes. Hypertriglyceridemia is the third most common cause of acute pancreatitis. The present report aimed to describe a case of hypertriglyceridemia-induced acute pancreatitis, where the therapeutic approach was plasmapheresis. A 48-year-old female patient was admitted to the hospital with complaints of “severe abdominal pain”. She reported the onset of such symptoms as nausea, vomiting and abdominal pain with a burning feeling in the epigastric area. The patient denied having a fever. The initial examination revealed that she was obese, oriented, tachypneic, normotensive, tachycardic, dehydrated, afebrile, anicteric and acyanotic and had normal color. Her abdomen was distended with bowel sounds, tympanic and diffusely painful, which was mostly in the supramesocolic compartment. The initial laboratory exams showed 10.932 mg/dL triglycerides, 1.548 mg/dL cholesterol, 226 mg/dL amylase and 899 mg/dL lipase. The abdominal computed tomography exhibited increased pancreatic volume (Balthazar E). The patient’s condition worsened, and she was sent to the intensive care center. Plasmapheresis was performed with no complications. On the 14th day after admission, the patient was discharged from the intensive care center and was sent to the gastroenterology ward, where an oral diet was resumed with good acceptance. The patient progressed well and was discharged from the hospital on the 25th day after admission. High triglyceride levels are necessary to cause pancreatitis, and it is important to exclude the most common causes. Importantly, the therapeutic approach reduced the high hypertriglyceridemia quickly, thereby avoiding tissue damage.

Source: PMID

Antioxidant Therapy Ineffective for Painful Chronic Pancreatitis.

Posted by

0


Pain scores were similar with antioxidants or placebo.

Most patients with chronic pancreatitis suffer from abdominal pain, often the most intransigent and debilitating symptom of the disease. Current treatments have shown limited effectiveness. The use of antioxidants has been the focus of several clinical trials, including a study in India that demonstrated improved pain symptoms with antioxidants (JW Gastroenterol Jul 24 2009).

To further investigate the efficacy of antioxidants, researchers conducted an industry-supported, randomized, placebo-controlled trial at a single center in the U.K. involving 92 patients with at least moderately severe pain occurring at least 7 days during the month prior to randomization. Patients received an antioxidant mixture (77 mg selenium yeast, 226.8 mg d-α-tocopherol, 252.6 mg ascorbic acid, 960 mg l-methionine, and 8.4 mg beta-carotene) 3 times daily or matching placebo for 6 months. Pain was scored on a visual analogue scale during the study visit and through a daily diary. Quality of life was assessed using four different validated instruments.

A total of 70 patients (76%) completed 6 months of therapy. Analyses of both pain scores and quality-of-life scores revealed no differences between groups.

Comment: The current findings are at odds with those of the recent trial in India, which demonstrated a clinically significant benefit of antioxidant therapy. These disparate results might be attributable to the differences in the antioxidant mixtures used or the patient populations studied. Compared with the current study cohort, the Indian cohort was younger, smoked less, and had more idiopathic disease than pancreatitis of alcoholic origin (which characterized the majority of the U.K. cohort). Unfortunately — in the U.S. at least — most patients with chronic pancreatitis fit the profile of the U.K. cohort. Taken together, these trials do not provide sufficient evidence to support the routine use of antioxidants in patients with painful chronic pancreatitis.

Source: Journal Watch Gastroenterology