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Key Points Question Are glucagon-like peptide-1 receptor agonists semaglutide and liraglutide, which were originally introduced for the treatment of type 2 diabetes and are frequently prescribed due to their weight loss properties, associated with disproportionately increased reporting of suicidality? Findings This disproportionality analysis through the case-control design based on the World Health Organization global database collecting suspected adverse drug reactions, identified a disproportionality signal of suicidal ideation with semaglutide, which remained significant when comparing semaglutide with dapagliflozin and metformin and in the subgroup of patients with coreported use of antidepressants and benzodiazepines. Meaning A detected signal of semaglutide-associated suicidal ideation warrants urgent clarification. Abstract Importance Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained use primarily due to their weight-reduction effects, although a regulatory review was undertaken for potential suicidality concern. Objectives To evaluate potential signals for suicidal and self-injurious adverse drug reactions (ADRs) associated with the GLP-1 RAs semaglutide and liraglutide. Design, Setting, and Participants Disproportionality analysis through the case-control design using the World Health Organization (WHO) global database of suspected ADRs. Participants were clinical patients worldwide experiencing an ADR suspectedly attributable to semaglutide or liraglutide in the database from inception to August 30, 2023. Data were analyzed from September to December 2023. Exposure Treatment with semaglutide or liraglutide regardless of indication or treatment duration. Main Outcomes and Measures Reporting odds ratio (ROR) and the bayesian information component (IC) with 95% CIs were calculated as measures of disproportionate reporting of suicidal and self-injurious ADRs associated with semaglutide and liraglutide compared with all other medications. Sensitivity analyses were conducted including patients with coreported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. A disproportionality signal was considered when the lower limits of the ROR and IC were above 1 and 0, respectively. Results A total of 107 (median [IQR] age 48 [40-56] years; 59 female patients [55%]) and 162 (median [IQR] age 47 [38-60] years; 100 female patients [61%]) cases of suicidal and/or self-injurious ADRs were reported between November 2000 and August 2023 with semaglutide and liraglutide, respectively. Significant disproportionality was detected only for semaglutide-associated suicidal ideation (ROR, 1.45; 95% CI, 1.18-1.77; IC, 0.53; 95% CI, 0.19-0.78), which remained significant in patients with coreported use of antidepressants (ROR, 4.45; 95% CI, 2.52-7.86; IC, 1.96; 95% CI, 0.98-2.63) and benzodiazepines (ROR, 4.07; 95% CI, 1.69-9.82; IC, 1.67; 95% CI, 0.11-2.65), when compared with dapagliflozin (ROR, 5.56; 95% CI, 3.23-9.60; IC, 0.70; 95% CI, 0.36-0.95), metformin (ROR, 3.86; 95% CI, 2.91-5.12; IC, 1.20; 95% CI, 0.94-1.53) and orlistat (ROR, 4.24; 95% CI, 2.69-6.69; IC, 0.70; 95% CI, 0.36-0.95). Conclusions and Relevance This study using the WHO database found a signal of semaglutide-associated suicidal ideation, which warrants urgent clarification.
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With the rising epidemic of obesity around the world, researchers are continuously searching for new ways to help individuals lose weight and improve their overall health. One of the most promising developments in this field is the use of semaglutide, a medication originally approved for treating type 2 diabetes, but now gaining attention for its potential to aid in weight loss.
Understanding Semaglutide
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that works by mimicking the effects of the natural hormone GLP-1. This hormone helps regulate blood sugar levels, decrease appetite, and promote weight loss. By activating GLP-1 receptors in the brain, semaglutide can help control hunger and food cravings, leading to reduced calorie intake and ultimately, weight loss.
In addition to its effects on appetite regulation, semaglutide also slows down the emptying of the stomach, making you feel full for longer after meals. This can help prevent overeating and snacking between meals, leading to more sustained weight loss over time.
The Benefits of Semaglutide for Weight Loss
1. Improved Weight Loss: Clinical trials have shown that individuals taking semaglutide in combination with diet and exercise experienced significantly greater weight loss compared to those following the same lifestyle changes without the medication. Participants in these studies lost an average of 15-20% of their body weight over a span of 1-2 years, demonstrating the effectiveness of semaglutide in promoting long-term weight loss.
2. Better Metabolic Health: Along with weight loss, semaglutide has been shown to improve other markers of metabolic health, such as blood sugar levels, cholesterol, and blood pressure. This makes it a valuable treatment option for individuals with obesity-related health conditions, such as type 2 diabetes and cardiovascular disease.
3. Sustainable Results: Unlike many fad diets and weight loss supplements, semaglutide offers a sustainable approach to weight loss that focuses on long-term lifestyle changes. By helping control appetite, decrease calorie intake, and improve satiety, semaglutide can support individuals in maintaining their weight loss goals over time.
Frequently Asked Questions about Semaglutide
1. Is semaglutide safe for weight loss?
Yes, semaglutide has been approved by the FDA for the treatment of obesity in individuals with a BMI of 30 or higher, or a BMI of 27 or higher with at least one weight-related health condition. However, it is important to talk to your healthcare provider before starting any new medication.
2. How long does it take to see results with semaglutide?
Most individuals start to see noticeable weight loss results within the first few weeks of starting semaglutide, with the full effects typically seen after several months of consistent use. It is essential to combine semaglutide with a healthy diet and regular exercise for optimal results.
3. What are the potential side effects of semaglutide?
Common side effects of semaglutide include nausea, vomiting, diarrhea, and constipation, especially when first starting the medication. These side effects typically improve over time as your body adjusts to the medication. However, if you experience severe or persistent side effects, it is important to contact your healthcare provider.
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