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Scientists comment on a report in the times on the number of deaths associated with obesity drugs.
Prof Ian Douglas, Professor of Pharmacoepidemiology, London School of Hygiene and Tropical Medicine, said:
“As with any medication, the weight loss jabs have known side effects. They are likely to have some unknown ones too, which by definition will be very rare. The Yellow Card scheme is one of the best ways we have to 1) give us an early warning of potentially unknown side effects and 2) help us to better characterise known side effects e.g. who’s most at risk, how severe are the effects, and do they resolve?
“What the Yellow Card scheme is not good for is quantifying the risks as we don’t know the total number of people exposed, nor the total number of adverse reactions which were actually caused by the drugs. So I wouldn’t give too much weight to the numbers being reported. They’re a reflection of the very common usage of these drugs and the fact that they are so prominent in the public eye. On an individual case report level, it’s often notoriously difficult to determine if the drug was the cause, and any evaluation has to take into account the background illnesses of the person experiencing the adverse effect. It’s the overall patterns revealed by the reports on mass which is helpful to doctors and scientists trying to determine the safety of medicines.
“I think the Times article was pretty balanced and clear.”
Prof Naveed Sattar, Professor of Cardiometabolic Medicine/Honorary Consultant, University of Glasgow, said:
“All medicines require ongoing monitoring, and regulators rightly continue to assess emerging safety signals. Reports of deaths in people taking weight loss medicines should be interpreted with caution and should not unnecessarily alarm the many people who are benefiting from these treatments.
“The people prescribed these medicines often already have conditions such as obesity, diabetes, high blood pressure, heart disease and kidney disease. These conditions themselves increase the risk of serious illness and premature death. As a result, when millions of individuals at higher risk take a medicine, some will inevitably experience major health events or die when on treatment, regardless of whether the medicine played any role. We do also know that because some individuals get these medicines privately those people won’t all necessarily have significant health conditions unlike those that get the medicines via the NHS – it’s important all those people report any problems to their doctors.
“The key question is not whether deaths occur among people taking a medicine, but whether the medicine changes the likelihood of death or serious disease compared with not taking it. The most reliable way to answer that question is through large randomised controlled trials comparing a medicine, whenever ethically possible, with placebo.
“The evidence from such trials for GLP-1 based medicines is reassuring. Across ten large cardiovascular outcome trials involving more than 71,000 people with diabetes, these medicines reduced the risk of death by around 12% compared with placebo, with no excess risk of pancreatitis https://pubmed.ncbi.nlm.nih.gov/40156846/. In the SELECT trial, involving more than 17,000 people with overweight or obesity and established cardiovascular disease, semaglutide reduced major cardiovascular events by 20% and nominally lowered deaths by 19% compared to placebo https://pubmed.ncbi.nlm.nih.gov/37952131/. Again, there was no evidence of excess risk of pancreatitis.
“For tirzepatide, definitive placebo-controlled cardiovascular outcome data are still awaited. However, current evidence from large clinical trials suggests benefits are likely to extend to reducing serious cardiovascular outcomes and possibly death, without evidence of increased pancreatitis risk – see these two papers for estimated benefits, https://pubmed.ncbi.nlm.nih.gov/41406444/ https://pubmed.ncbi.nlm.nih.gov/41940793/. Ongoing trials should provide greater certainty.
“Beyond weight loss, these medicines have also been shown in randomised trials to improve a range of obesity-related conditions, including type 2 diabetes, obstructive sleep apnoea, heart failure symptoms, obesity-related liver disease, blood pressure, knee pain linked to arthritis, kidney outcomes and quality of life. And there are ongoing trials in many other chronic conditions.
“This does not mean there are no safety concerns. All medicines require ongoing monitoring, and regulators rightly continue to assess emerging safety signals. However, as the Times article also says, we can’t assume that all adverse events reported via the Yellow Card scheme were caused by the medicine. The strongest evidence comes from well-conducted randomised trials, which compare similar groups of people receiving either the medicine or placebo and provide the clearest assessment of overall benefits and risks. This is why whenever possible regulators and health authorities place most reliance on randomised trials as these get us closest to the truth.”
Dr Marie Spreckley, research programme manager and researcher, Prevention of Diabetes and Related Metabolic Disorders in High Risk Groups, University of Cambridge, said:
“The MHRA Yellow Card scheme is an important tool for identifying potential safety signals, but these data need to be interpreted quite carefully. As the Times article makes clear, Yellow Card reports are voluntary, self-reported, multiple reports may relate to the same individual, and they cannot establish that a medicine caused the reported event.
“Overall, the evidence continues to show that these medicines provide substantial health benefits for many people when prescribed appropriately, although, like all medicines, they can cause rare but serious adverse effects. Continued pharmacovigilance and careful patient monitoring definitely remain essential.”
Prof Penny Ward, Visiting Professor in Pharmaceutical Medicine, Kings College London, said:
“GLP-1 agonist medications are increasingly prescribed in the UK to aid weight loss as well as to treat diabetes with an estimated 1.5 million people taking these medications annually at this time. It is therefore not surprising that the MHRA have received so many adverse event reports.
“Gastrointestinal events are by far the most common adverse events associated with these agents and range from simple nausea, or vomiting to more serious reports including pancreatitis and effects on gut motility leading, rarely, to perforation. Some have regrettably resulted in a fatal outcome.
“These findings reiterate the importance of prescribing these medicines carefully for selected patients at most need and with full explanation of potential risks so that patients are aware of the symptoms and signs of more serious concerns. Patients presenting with gastrointestinal symptoms, particularly abdominal pain, should be promptly seen and investigated to enable appropriate management.”
https://www.thetimes.com/uk/healthcare/article/reports-deaths-mounjaro-weight-loss-jabs-smbvtqlst
Declared interests
Prof Ian Douglas: “Research grants from GSK and shares in GSK.”
Prof Naveed Sattar: “NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Janssen, Kailera, Mass Medicines, Menarini-Ricerche, Merck Sharp & Dohme, Metsera, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, UCB Pharma and Verdiva Bio; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche. He does not hold any stocks or shares in any medical companies. He is Chair of the Obesity Healthcare Goals Programme for Office for Life Sciences, HM Government.”
Dr Marie Spreckley: “No conflicts of interest to declare.”
Prof Penny Ward: “Visiting Professor, Pharmaceutical Medicine at Kings College London, past employee of multiple pharma and biotech companies and currently director of a consultancy company advising on the development and licensing of medicines.”