Tag: GLP-1 agonist

Categories : Gastrointestinal Surgeries & ProceduresTags :

Hold the GLP-1 Agonists Before Surgery, New Advice Says

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Photo by Natanael Melchor on Unsplash

Patients taking Glucagon-like peptide-1 (GLP-1) receptor agonists should stop taking them before they have surgery, due to the risk of aspirating while under general anaesthesia. This is the latest advice from the American Society of Anesthesiologists (ASA).

Initially approved by the Food and Drug Administration (FDA) for type 2 diabetes mellitus and cardiovascular risk reduction, GLP-1 agonists have shot up in popularity due to their effectiveness in weight loss. Despite having recent FDA approval, they have been used off-label for this purpose for quite some time.

When it comes to surgery, a number of organisations have recommended to hold these drugs either the day before or day of the procedure. For patients on weekly dosing, it is recommended to hold the dose for a week, the ASA notes.

GLP-1 agonists are associated with adverse gastrointestinal effects such as nausea, vomiting and delayed gastric emptying. The effects on gastric emptying are reported to be reduced with long-term use, most likely through rapid tachyphylaxis at the level of vagal nerve activation. Based on recent anecdotal reports, there are concerns that delayed gastric emptying from GLP-1 agonists can increase the risk of regurgitation and pulmonary aspiration of gastric contents during general anaesthesia and deep sedation. Patient taking GLP-1 agonists are more likely to have increased residual gastric contents as predicted by adverse gastrointestinal symptoms (nausea, vomiting, dyspepsia, abdominal distension).

The use of GLP-1 agonists in paediatrics has primarily been reported for the management of type 2 diabetes mellitus and obesity. The published literature on GLP-1 agonists in paediatrics is predominantly from paediatric patients 10 to 18 years old and concerns are similar to those reported in adults. During the conduct of general anaesthesia/deep sedation, children on GLP-1 agonists have similar gastrointestinal adverse events at a rate similar to adults.

In a review of the literature, the ASA Task Force on Preoperative Fasting found that, beyond a few case reports, there was little evidence for guidance on preoperative management of GLP-1 agonists. Nevertheless, they made recommendations for elective procedures. In the case of urgent or emergent procedures, they suggested treating the patient as ‘full stomach’.

If the patient’s GLP-1 agonists prescribed for diabetes management are held for longer than the dosing schedule, the guidelines urge surgeons to consider consulting an endocrinologist for bridging the antidiabetic therapy in order to avoid hyperglycaemia.

They further recommend that if gastrointestinal symptoms, such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain, are present, surgeons should consider delaying elective procedures. If the patient has no gastrointestinal symptoms and the GLP-1 agonists have been held as advised, the surgical team can carry on as normal.

Source: American Society of Anesthesiologists

Categories : Gastrointestinal Metabolic DisordersTags :

For Weight Loss, the Side Effects of GLP-1 Agonists can be Hard to Stomach

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Photo by Andres Ayrton on Pexels

GLP-1 agonists are being lauded as game-changers in the fight against obesity, but GLP-1 agonist drugs like semaglutide may come with a heightened risk of severe gastrointestinal problems, according to new research published in JAMA.

Designing their study for the side effects rather than the efficacy of the drugs, the researchers found that GLP-1 agonists are associated with an increased risk of serious medical conditions including gastroparesis (stomach paralysis), pancreatitis and bowel obstruction.

While previous studies highlighted some of these risks in patients with diabetes, this study from the University of British Columbia is the first large, population-level study to examine adverse gastrointestinal events in non-diabetic patients using the drugs specifically for weight loss.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said first author Mohit Sodhi, a graduate of UBC’s experimental medicine program and fourth year UBC medical student studying the adverse events of commonly prescribed medications. “The risk calculus will differ depending on whether a patient is using these drugs for diabetes, obesity or just general weight loss. People who are otherwise healthy may be less willing to accept these potentially serious adverse events.”

GLP-1 agonists have exploded in popularity over the past decade as an off-label weight-loss tool, reaching approximately 40 million prescriptions in the US in 2022.

It was only in 2021 that some forms of the medications were approved as a treatment for obesity. However, randomised clinical trials examining the efficacy of the medications for weight loss were not designed to capture rare gastrointestinal events due to their small sample sizes and short follow-up periods.

“There have been anecdotal reports of some patients using these drugs for weight loss and then presenting with repeated episodes of nausea and vomiting secondary to a condition referred to as gastroparesis,” said senior author Dr Mahyar Etminan, an epidemiologist and associate professor in the department of ophthalmology and visual sciences at the UBC faculty of medicine. “But until now, there hasn’t been any data from large epidemiologic studies.”

To help fill this knowledge gap, UBC researchers examined health insurance claim records for approximately 16 million US patients and looked at people prescribed either semaglutide or liraglutide, two main GLP-1 agonists, between 2006 and 2020. They included patients with a recent history of obesity, and excluded those with diabetes or who had been prescribed another antidiabetic drug.

The researchers analysed the records to see how many patients developed one of four gastrointestinal conditions, and compared that rate to patients using another weight-loss drug, bupropion-naltrexone. Compared to bupropion-naltrexone, GLP-1 agonists were associated with a:

  • 9.09 times higher risk of pancreatitis, which can cause severe abdominal pain and, in some cases, require hospitalisation and surgery.
  • 4.22 times higher risk of bowel obstruction, resulting in symptoms like cramping, bloating, nausea and vomiting. Depending on the severity, surgery may be required.
  • 3.67 times higher risk of gastroparesis, limiting the passage of food from the stomach to the small intestine and results in symptoms like vomiting, nausea and abdominal pain.

Additionally, the study found a non-significant higher incidence of biliary disease.

The researchers say that although the events are rare, with millions around the world using the drugs, it could still lead to hundreds of thousands of people experiencing these conditions.

“These drugs are becoming increasingly accessible, and it is concerning that, in some cases, people can simply go online and order these kinds of medications when they may not have a full understanding of what could potentially happen. This goes directly against the mantra of informed consent,” said Sodhi.

In the meantime, the researchers hope that regulatory agencies and drug makers will consider updating the warning labels for their products, which currently don’t include the risk of gastroparesis.

“This is critical information for patients to know so they can seek timely medical attention and avoid serious consequences,” said Sodhi.

Source: University of British Columbia

Categories : Cardiovascular Disease Metabolic DisordersTags :

Semaglutide Also Cuts Cardiovascular Risk, Could Change Cardiology Practice

On By ModernMedia
By HualinXMN – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=133759262

According to results from the SELECT trial run by Novo Nordisk, semaglutide dramatically reduces the risk of major adverse cardiovascular events (MACEs) in addition to its obesity benefits. This is bolstered by the results of another trial, STEP-1, which also suggested significant reduction in future cardiovascular events. These results have captured the attention of researchers, who commented in Nature that they could change the practice of cardiology.

Semaglutide, sold in the US for the treatment of both obesity (Wegovy) and diabetes (Ozempic), is an agonist for glucagon-like peptide 1 (GLP-1), a hormone associated with appetite.

”It’s hard to think of other [drugs], apart from statins, that have shown such a profound effect,” says Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center in Los Angeles, USA.

It was expected that semaglutide would have cardiovascular benefits through promoting weight loss, but evidence shows that drugs mimicking GLP-1 can improve fatty-acid metabolism and reduce inflammation, for example, says Gulati. “This is what’s so fascinating about these drugs. They work on the brain, the pancreas, the cardiovascular system, the gastrointestinal tract … There’s more to them than simply weight loss.”

Recent studies have been encouraging in terms of semaglutide’s benefits for reducing cardiovascular disease risk. Earlier this month, Novo Nordisk announced the headline results from the SELECT cardiovascular outcomes trial. The double-blinded trial compared subcutaneous once-weekly semaglutide 2.4mg with placebo as an adjunct to standard of care for prevention of MACEs over a period of up to five years. The trial enrolled 17 604 adults aged 45 years or older with overweight or obesity and established cardiovascular disease (CVD) with no prior history of diabetes.

The trial showed 20% reduction in MACEs for people treated with semaglutide 2.4mg compared to placebo. The primary endpoint was a composite outcome of the first occurrence of MACE cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. All three of these components contributed to the MACE reduction. 1270 first MACEs were accrued.

Expanding GLP-1 analogues to cardiovascular disease prevention may not be without challenges, as the European Medicines Agency opened investigations into semaglutide and liraglutide over reports of suicidal thoughts and self-harm.

A separate study based on the STEP 1 trial data found that 93 million adults in the US could benefit from semaglutide, from a combination of weight loss and reduced cardiovascular benefits. They estimate a reduction in relative risk of 18% with the drug.