According to a recent study, individuals who utilize commonly administered medications for weight loss, namely Wegovy, Ozempic, Saxenda, and Victoza, may face an elevated susceptibility to severe gastrointestinal complications, such as gastric dysmotility, pancreatitis, and intestinal obstructions, in comparison to individuals employing alternative forms of weight loss medications.
The study revealed that the occurrence of these events in individual patients seems to be infrequent, with approximately 1% of individuals who were administered Ozempic being diagnosed with stomach paralysis.However, there has been a significant increase in demand for these drugs, resulting in a global consumption of tens of millions.According to researchers, even infrequent risks such as the ones mentioned may result in a substantial increase of hundreds of thousands of new cases.
According to Dr. Mahyar Etminan, an epidemiologist at the University of British Columbia, the utilization of these drugs by a large population entails that even a 1% risk can potentially affect a significant number of individuals.
The authors of the study also emphasize that these issues are not of a mild nature.Bowel obstructions, such as those encountered in medical emergencies, can pose significant health risks.
Earlier CNN coverage brought attention to instances of gastric dysmotility in individuals who had consumed these medications, as well as the absence of explicit notification regarding this particular adverse reaction provided to patients.
The prescribing information for Wegovy and Saxenda includes warnings regarding various severe adverse effects, such as pancreatitis, gallbladder disorders, intestinal obstruction, renal impairment, severe allergic reactions, tachycardia, suicidal ideation, and alterations in visual acuity in individuals with comorbid diabetes. Additionally, the warning label for Ozempic has been updated to include a cautionary note regarding ileus, a condition characterized by intestinal blockage.
The labels additionally indicate that the most prevalent adverse effects include nausea, vomiting, and constipation. Furthermore, individuals with a documented medical history of specific hereditary thyroid cancers are strongly advised against the utilization of said medications.
In the present study, which was published as a research letter in the Journal of the American Medical Association (JAMA), a team of researchers from the University of British Columbia conducted an examination of a representative subset of over 16 million insurance claims sourced from a prescription drug database. This database encompasses approximately 93% of all outpatient prescriptions in the United States.The claims were submitted within the time frame spanning from 2006 to 2020.
The researchers sought individuals who had been prescribed two parenterally administered medications, namely semaglutide and liraglutide. Both medications are classified as GLP-1 agonists and exhibit the ability to decelerate gastric emptying. These interventions have the potential to assist individuals with diabetes in managing their blood glucose levels and can result in significant weight reduction for both diabetic and non-diabetic individuals.
Semaglutide was granted approval by the US Food and Drug Administration in 2021 for the purpose of weight loss in individuals who are obese but do not have diabetes.The medication is marketed as Ozempic when prescribed for diabetes management and as Wegovy when prescribed for weight loss purposes.Liraglutide has been granted approval by the Food and Drug Administration (FDA) as a pharmaceutical intervention for weight loss since the year 2014.When utilized as a treatment for diabetes, the medication is referred to as Victoza, whereas when employed for the purpose of weight management, it is known as Saxenda. However, prior to the official release of these medications for weight loss purposes, physicians had already observed their advantageous effects and started prescribing them off-label to patients requiring weight reduction.
In order to identify the individuals in question, the researchers sought out patients who had received a diagnosis of obesity at least 90 days prior to commencing the medication. Furthermore, individuals who had been diagnosed with diabetes or were concurrently using any other medication to regulate their blood sugar levels were excluded from the study.
Subsequently, a comparison was made between the incidence rates of severe gastrointestinal complications among the aforementioned patients and individuals who were administered an alternative weight loss medication, namely bupropion-naltrexone, marketed as Contrave in pill form.
Throughout the duration of the study, the researchers observed a notable disparity in the incidence of severe gastrointestinal complications between individuals administered with Ozempic and Saxenda, as opposed to those receiving Contrave.
In terms of absolute values, the group administered with Ozempic exhibited a new case rate of stomach paralysis at approximately 1%, while the group receiving Saxenda displayed an incidence of stomach paralysis at around 0.7%. Additionally, the group taking Contrave demonstrated an incidence of stomach paralysis at approximately 0.3%.
In terms of relative risk, individuals who received the injected drugs exhibited a more than threefold increased likelihood of developing stomach paralysis in comparison to those who were administered Contrave.
No instances of bowel obstructions were observed in the cohort receiving Ozempic. However, the research revealed a prevalence of 0.8% among individuals using Saxenda and a prevalence of 0.17% among those using Contrave.The incidence of bowel obstructions was found to be over four times higher in individuals receiving the injected medications as opposed to those using Contrave.
In the case of pancreatitis, the incidence rates were found to be 0.5% for individuals using Ozempic, 0.8% for those using Saxenda, and 0.01% for individuals taking Contrave. This data indicates a significant increase of over nine times in the risk of pancreatitis when comparing the aforementioned medications.
The investigation also encompassed an examination of the potential hazard of patients receiving a diagnosis of biliary disease, a collection of ailments that impact the gallbladder and bile ducts. However, no noteworthy disparities were observed between the various cohorts.
Among the cohort of approximately 600 individuals receiving Ozempic, a total of four instances of gastroparesis, two occurrences of pancreatitis, no incidents of bowel obstructions, and five cases of biliary disease were observed.
Among the cohort of approximately 4,400 individuals who were administered Saxenda, a total of 66 instances of gastric paralysis, 73 occurrences of bowel obstructions, 71 cases of pancreatitis, and 162 incidents of biliary disease were reported.
In the cohort of approximately 650 individuals who were administered Contrave, it was observed that three instances of gastric paralysis, two occurrences of bowel obstructions, one case of pancreatitis, and 16 instances of biliary disease were reported.
The research has certain limitations. The nature of this study is observational, thus limiting its ability to establish causality and only allowing for the identification of associations. The drugs’ causal relationship with the diagnosed conditions cannot be definitively established.
However, the researchers made efforts to mitigate potential biases that could have influenced their findings.
According to Mohit Sodhi, a medical student researching the adverse events associated with commonly prescribed medications, individuals with diabetes are already at a heightened risk of developing gastroparesis, pancreatitis, and biliary disease.According to Sodhi, the exclusion of certain subjects from the study allowed for a more meticulous examination of the potential associations between the drug and the disease.
Despite the researchers’ efforts to identify individuals who potentially employed the drugs for weight reduction purposes, the absence of explicit documentation in their medical records precludes definitive confirmation of such intentions.
However, it is noteworthy that this study represents the initial attempt by researchers to quantify the aforementioned risks, which were previously only subjectively reported by medical professionals and individuals who personally experienced them.
According to independent experts who were not affiliated with the study, the research was conducted in a commendable manner. However, they have identified certain limitations and caution against regarding it as the definitive conclusion on the matter.
According to Dr. Ian Musgrave, a molecular pharmacologist at the University of Adelaide in Australia, who provided a statement on the study to the non-profit Science Media Centre in the UK, GLP-1 agonists are generally well tolerated with a low occurrence of severe adverse effects.
As an illustration, Musgrave (year) posited that the occurrence of pancreatitis, an inflammatory condition affecting the pancreas, has been established as a recognized adverse outcome in individuals with type-2 diabetes who are exposed to these therapeutic agents. The extent to which patients utilizing these medications for the purpose of weight reduction may experience comparable adverse effects remains uncertain.
Musgrave noted that a potential factor influencing the study results is the disparity in patient populations, with a significantly larger number of individuals receiving injected drugs compared to those receiving Contrave. Another potential consideration is that although the researchers implemented measures to account for variables such as age, gender, alcohol consumption, smoking, and high cholesterol, they did not assess the impact of body mass index (BMI).
However, the individual expressed that the findings of the study constitute a significant contribution to medical practitioners who are engaged in prescribing these medications, as well as to patients who are contemplating their usage. CNN contacted Novo Nordisk, the manufacturer of the injectable weight loss drugs analyzed in this study, to request a statement.
Novo Nordisk, the pharmaceutical company responsible for producing Ozempic and Saxenda, has expressed its unwavering support for the safety and effectiveness of all its GLP-1 medications, provided they are utilized in accordance with the prescribed product labeling and approved indications.
The company stated to CNN that, in relation to the study, the authors themselves acknowledge certain limitations, such as the possibility of confounding by indication and other factors.
It is advisable for patients to adhere to the prescribed medications for their approved indications while being under the guidance and monitoring of a healthcare professional. According to the statement, it is recommended that treatment decisions involving the use of a GLP-1 should be a collaborative effort between the patient and a healthcare provider. This is because the healthcare provider is able to assess the suitability of using a GLP-1 based on an evaluation of the patient’s unique medical profile.
The researchers acknowledge that the aforementioned issues likely did not manifest during the clinical trials that facilitated the approval of the treatments. This can be attributed to the insufficient sample size of those studies, which hindered the detection of certain infrequent negative occurrences. Alternatively, it is possible that these events were documented solely as symptoms without further exploration into their root causes.
According to Sodhi, the primary manifestations of gastroparesis include nausea and vomiting. Therefore, individuals experiencing gastroparesis may present symptoms of nausea and vomiting. However, it is important to examine the underlying cause of these symptoms.
Sodhi expressed his motivation to conduct the study subsequent to providing medical care to an individual in the emergency department who exhibited symptoms of vomiting at a frequency of 15 to 20 occurrences per day.The medical practitioners were unable to ascertain the etiology until they observed the patient’s concurrent administration of Ozempic. According to Sodhi, the individual was administered a medication targeting gastric dysmotility, resulting in significant improvement in their condition.
The speaker expressed the possibility that he experienced such an adverse event.
Meanwhile, the researchers express their anticipation for regulatory agencies and pharmaceutical companies to contemplate revising the warning labels associated with their products. Presently, these labels fail to incorporate the potential hazard of gastroparesis.
According to Sodhi, it is imperative for patients to be aware of this crucial information in order to promptly seek medical attention and prevent the occurrence of severe consequences.
The researchers aspire that their study will enable individuals to make more informed decisions regarding pharmaceutical substances.
According to Sodhi, individuals with diabetes who are prescribed this medication may exhibit a greater inclination to tolerate the infrequent occurrence of these adverse events, as they prioritize the management of their diabetes.
However, individuals who are in good health but desire to shed some weight may be more inclined to consider taking these medications if they possess a more comprehensive understanding of the potential implications involved.
