This is the 4716th article of Da Yi Xiao Nursing
On July 11, 2023, the European Medicines Agency (EMA) announced on its official website that it would start a review of three Novo Nordisk products, including Ozempic (semaglutide), Saxenda (liraglutide) and Wegovy (semaglutide). The reason for the investigation was that the Icelandic health regulator had previously identified three cases of patients with suicidal tendencies. These include two cases using Ozempic and one case using Saxenda.
So is the use of GLP-1 receptor agonists such as liraglutide and semaglutide really suicidal? Next, the pharmacist will give you a science popularization
So will the use of GLP-1 receptor agonists such as liraglutide and semaglutide lead to suicide? Next, Xiao Renhe will give you a science popularization~~~
What are GLP-1 receptor agonists?
In October 2022, Tesla CEO Elon Musk posted that he lost 9 kilograms in a month, and the secret is to fast regularly and use semaglutide. Both liraglutide and semaglutide are glucagon-like peptide-1 (GLP-1) receptor agonists, and both have a role in weight loss. Although suicidal tendencies are not listed as a side effect, in the United States, the semaglutide label contains warnings about suicidal behavior and suicidal tendencies. In December 2021, the Drug Evaluation Center of the State Food and Drug Administration issued the "Technical Guidelines for Clinical Trials of Weight Control Drugs", which proposed that some weight control drugs (such as drugs with a central mechanism of action) may cause neuropsychiatric adverse events (such as depression and suicidal tendencies, agitation, anxiety, insomnia, psychotic reactions, attention disorders). For this reason, concerns have been raised about the risk of adverse events associated with suicide with GLP-1 receptor agonists such as liraglutide and semaglutide.
Can the use of GLP-1 receptor agonists such as liraglutide and semaglutide cause suicide?
(1) The correlation of liraglutide and semaglutide in suicide adverse events was analyzed by four algorithms: ROR, PPR, BCPNN and MGPS, and the results were probably not related.
(2) Gamble JM et al. excluded patients with a history of depression, self-harm, and other serious psychiatric disorders, and compared the incidence of GLP-1 receptor agonists with other glucose-lowering drugs in people with new-onset depression or self-injury, and found that there was no clinical correlation between GLP-1 receptor agonists and depression or self-harm.
(3) In O'Neil PM et al., individuals with a body mass index of ≥ 30 or ≥27 kg/m2 with weight-related comorbidities were randomly assigned to liraglutide 3.0 mg (n = 3384) or placebo (n = 19410) subcutaneously once daily, and 9 (0.3%) liraglutide and 2 (0.1%) were found. Adverse events of suicidal ideation were reported in the placebo group, but there was no difference in suicide-related measures at a later prospective assessment. In addition, 9 of the 11 patients reported a history of previous psychiatric illness (including depression, anxiety, and insomnia) or stress associated with other life events.
(4) It is well known that patients with depression are at higher risk of suicide and self-harm. Mezuk B et al. found that clinically diagnosed diabetes was associated with a 4.3-fold increase in the incidence of depression, and this relationship was more pronounced for prediabetes and type 2 diabetes, with clinically diagnosed diabetes associated with a 1.8-fold increase in the use of antidepressants.
(5) Studies have shown that the prevalence of current depression, lifetime diagnosis of depression and anxiety is significantly higher in men and women who are overweight (BMI: 25-30 kg/m2), and the likelihood of current depression or lifetime diagnosis of depression and anxiety is significantly higher in men with grade III obesity (BMI≥40 kg/m2). In addition, GLP-1 receptor agonists achieve weight loss by inhibiting the appetite center, slowing down intestinal peristalsis, delaying gastric emptying, and reducing food intake. There is evidence that appetite suppressant drugs often affect the appetite centers of the central nervous system and may have other central nervous system effects such as excitement, insomnia, depression, etc.
In summary, there is no evidence that GLP-1 receptor agonists such as liraglutide and semaglutide directly cause suicide adverse events, which may be the result of multiple factors such as drugs and self-disease (diabetes, obesity). Whether there is a necessary causal relationship between the two needs to be evaluated by large-scale clinical studies.
Tips
In China, semaglutide has no indication for weight loss, and patients without diabetes cannot use it in the formal way at this stage. Although "slimming injections" can reduce the weight of some people to a certain extent and achieve the effect of "weight loss", the over-publicized weight loss effect may cause chaos in the medical beauty industry, so that people who really need to use drugs cannot use them, while people who do not need to use drugs abuse drugs, causing varying degrees of damage to the human body.
Therefore, pharmacists advise: don't put your hopes for weight loss on semaglutide injections, leave the medicine to those who really need it!
bibliography
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[2]https://www.cde.org.cn/main/news/viewInfoCommon/75001677bbb075c037afff20e96461d1
[3] Gamble JM, Chibrikov E, Midodzi WK, Twells LK, Majumdar SR. Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink. BMJ Open. 2018 Oct 8; 8(10):e023830.
[4] O'Neil PM, Aroda VR, Astrup A, Kushner R, Lau DCW, Wadden TA, Brett J, Cancino AP, Wilding JPH; Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials. Diabetes Obes Metab. 2017 Nov; 19(11):1529-1536.
[5] Mezuk B, Johnson-Lawrence V, Lee H, Rafferty JA, Abdou CM, Uzogara EE, Jackson JS. Is ignorance bliss? Depression, antidepressants, and the diagnosis of prediabetes and type 2 diabetes. Health Psychol. 2013 Mar; 32(3):254-63.
[6] Zhao G, Ford ES, Dhingra S, Li C, Strine TW, Mokdad AH. Depression and anxiety among US adults: associations with body mass index. Int J Obes (Lond). 2009 Feb; 33(2):257-66.
[7] Petry NM, Barry D, Pietrzak RH, Wagner JA. Overweight and obesity are associated with psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychosom Med. 2008 Apr; 70(3):288-97.
[8] LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Weight Loss Agents. 2020 Jun 5.
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