Boiler-Plate Response to Heightened Drug Toxicity

"[Data from the study are not sufficient to establish a cause-and-effect association between semaglutide and NAION]; key methodological limitations of the study [need to be considered when interpreting the findings]."

"Patient safety is a top priority for Novo Nordisk, and we take all reports about adverse events from the use of our medicines very seriously."

"Semaglutide has been studied in large real world evidence studies and robust clinical development programs with a cumulative exposure including from post-marketing use of over 22 million patient years."

"The totality of data provides reassurance of the safety profile of semaglutide." Novo Nordisk

Semaglutide is most commonly known under the brand names Wegovy and Ozempic. Photograph: Reuters

A new American study has found that drugs containing the active compound semaglutide have a potential side-effect among certain users, presenting a dilemma in outcome.Last summer researchers at Mass Eye and Ear in Boston, Mass felt motivated to begin an investigation on whether the sought-after weight-loss drugs might be associated with increased risk of NAION. Their interest was piqued after three patients were diagnosed with a  relatively rare eye condition.

The study conclusion was that Ozempic and other weight-loss drugs -- so hugely popular -- contain the active compound semaglutide, associated with increased risk of NAION, (nonarteritic anterior ischemic optic neuropathy). An eye-loss condition affecting two to ten in every 100,000 people annually. Sudden and permanent loss of vision in one eye as a result of insufficient blood flow and oxygen to optic nerves. The condition is also referred to as an "eye stroke", a significant cause of adult blindness.

 

Three patients at the Harvard Medical School who took semaglutide were diagnosed within the same week with AION. Published in JAMA Ophthalmology, the study found people who were prescribed semaglutide became seven times likelier to end with a diagnosis of NAION than were people prescribed different drugs for an overweight condition. Semaglutide prescribed for Type 2 diabetes saw people becoming four times more likely to be threatened with the rare eye diagnosis.

 

Getty Images

"Our main finding is that prescribed semaglutide is associated with an increased risk of NAION", the researchers concluded. "We should be confident that if corroborated, the absolute risk of developing NAION in direct relation to taking semaglutide must indeed be rare", wrote University of Birmingham professor Dr. Susan Molan, who investigates rare diseases of the eye and brain. The findings "should be viewed as significant but tentative", cautioned Dr. Joseph Rizzo, director of the neuro-ophthalmology service at Mass Eye and Ear. 

 

Ozempic and Wegovy are in a class of drugs  called GLP-1 agonists, spurring the release of insulin, and lowering blood sugar, but act as well on the brain to curb appetite. Given through a once-weekly injection by a prefilled pen. A survey by Dalhousie University's Agri-Food Analytics lab, partnering with market research firm Caddle, found some ten percent of the Canadian adult population uses a GLP-1 type drug for diabetes control, weight loss, or both. 

 

Reports of potential unforeseen side-effects inclusive of gastrointestinal problems and unplanned pregnancies have arisen with the growing popularity of the drug. The research team studied records of patients referred to their clinic from 2017 through to 2023, checking for NAOIN diagnoses. Records of close to 17,000 patients treated over six years were analyzed. Among them 629 NAION cases were diagnosed in that six-year period.

 

Divided into two groups those diagnosed with Type 2 diabetes and people living with obesity were separated to compare people who received prescriptions for semaglutide along with those taking other diabetes or weight-loss drugs. Among those with diabetes, 8.9 percent of the semaglutide-treated group developed NAION within three years of follow up, compared to 1.8 percent for the non-semaglutide group.

 

5.7 percent in the semaglutide group of overweight or obese people were diagnosed with NAION, as opposed to 0.8 percent of those prescribed drugs other than semaglutide. 

Some of the most common for semaglutide include:

• nausea
• vomiting
• diarrhoea
• stomach pain
• constipation

 

A box of Ozempic and contents. 

George Frey | Reuters

            

Miracle Drug? No

"This could all be not a real issue, but when you're talking about perioperative aspiration that can cause death, I think we need to act out of an abundance of caution."

"Urgent and high quality research [needs to be done to figure out what the problem is, if any]."

"The reason why people come to the operating room fasted is for an important reason: we want the stomach to be empty to reduce the chance of aspiration."

"[The drugs are of] potential enormous public health importance [taking into account staggering rates of obesity and Type 2 diabetes]."

"[If there is a] legitimate [link between the weight loss drugs and suicidal ideation] it is undoubtedly rare."

Dr. Philip Jones, professor of anesthesiology, Mayo Clinic

Deputy editor-in-chief Canadian Journal of Anesthesia

"[My concern is that the] vigorous  advertising on U.S. television that shows Ozempic users happily doing yoga or playing pickle ball [could obscure the fact that they're] serious medications with a variety of possible side-effects."

"It's not a miracle drug as so many social media sites claim. There are no miracles in science."

Dr. Joe Schwarcz, director, Office for Science and Society, McGill University

Whether they're plastered over streetcars or displayed at Toronto Blue Jays games, advertisements for Ozempic — a diabetes drug that's increasingly being used for weight loss — seem to be everywhere.

Over 3.5 million prescriptions to the value of close to $1.2 billion were dispensed in Canada in 2022 for Ozempic. It is so popular as a weight-loss drug that its manufacturer, Novo Nordisk, announced a temporary shortage of its one milligram Ozempic injection pen for the Canadian market to commence late August and continue to early October; the global supply constraints and increased demand for the product as a guaranteed money-maker for the pharmaceutical company. 

With the growing popularity of these drugs, reports of possible adverse reactions are emerging. Among them recent stories including a possible increased risk of "gastroparesis", a condition affecting nerves and muscles of the stomach, and as well, suicidal ideation in users. Experts feel no evidence exists of cause-and-effect relationships. Should there be a "legitimate" link between weight loss drugs and suicidal ideation "It is undoubtedly rare".

A small number of people who have taken Ozempic have reported developing suicidal thoughts. Chelsea Stahl / NBC News; Getty Images

The drugs are typically taken through once-weekly injections of a pre-filled pen. The medication works partially through delaying gastric emptying, where food remains in the stomach longer before it reaches the intestines, and thus having the effect of making people feel well fed for a longer period of time. The issue of pulmonary aspiration, leading to pneumonia, respiratory distress and possibly death has arisen as a concern among American and Canadian anesthesiologists, as a "signal of concern".

Which is to say, a potentially life-threatening complication for patients undergoing surgery; the risk specifically of such patients regurgitating stomach contents under sedation, and inhaling food into their lungs. A smattering of case reports and small observational studies have arisen relating to patients taking Ozempic or related drugs among whom significant amounts of food remained in their stomachs while under anesthesia, even after 18 hours of fasting.

In a recently published editorial, Dr. Philip Jones who joined he Mayo Clinic recently, following 20 years at Western University, recommend along with his co-authors, that people taking the drugs for weight loss consider halting them for a three-week period prior to undergoing sedation. Three weeks appears to be how long a time it would take for the  body to clear 90 percent of the pharmaceuticals.

These drugs are in the class known by the name glucagon-like peptide-1 (GLP-1) receptor agonists, which mimic a natural hormone serving to delay transit of food through the stomach. Semaglutide is the active ingredient in Ozempic and Wegovy. For over 15 years, semaglutide has been used in the treatment of diabetes. The drug decreases appetite at  higher doses by affecting the brain's hunger centres, and slowing "gastric emptying".

 

According to Dr. Jones and his colleagues' editorial published in the Canadian Journal of Anesthesia, the "gastric emptying" effect explains the common complaints of nausea, diarrhea, vomiting and other gastro-related issues with use of the drug. It is that very delayed gastric emptying that may pose a serious threat to surgery patients "by increasing the risk of pulmonary aspiration of regurgitated gastric contents" they wrote.

The drug is undergoing an assessment as well, by Health Canada, as to whether there is any association between the GLP-1 class and increased risk of thoughts of suicide or self-harm.Drug regulators in the United States and United Kingdom along with the European Medicines Agency launched similar probes. The European agency last month stated it is in the process of analyzing some 150 reports of possible cases of self-injury and suicidal thoughts in people taking GLP-1 receptor antagonists, that include Ozempic, Wegovy and Saxenda.

In addition to which, some reports have surfaced about severe gastroparesis -- paralysis of the stomach where the muscles of the stomach fail to move normally. Contractions become weaker and slower than what is required to digest food and propel it through the digestive tract. A Louisiana patient who used Ozempic for a year before switching to a newer, related drug in July claims to have suffered excessive vomiting from gastroparesis to the extent that her teeth fell out.

Ozempic, which is used to treat Type 2 diabetes and obesity, is among medications containing GLP-1 receptor agonists that are under review by Health Canada over concerns of suicide risk. (Joel Saget/AFP/Getty Images)

"Patient safety is of utmost importance to Novo Nordisk and we take all reports about adverse events from use of our medicines very seriously."

"Our team is continuously monitoring the safety profile of our products and collaborating closely with health authorities to ensure patient safety information, including adequate information on side-effects, are included in the product monograph."

"[We] remain confident in the benefit risk profile [of our drugs]."

Kate Hanna, director of communications, Novo Nordisk Canada