Objective: We aimed to evaluate alirocumab- and evolocumab-related adverse events (AEs) in real-world compared with all other drugs, overall and by gender and age subgroups; we also aimed to compare their risks of cognitive impairment, musculoskeletal disorders and diabetes with various statins and ezetimibe.Methods: We retrospectively extracted AE reports from the FDA Adverse Event Reporting System (FAERS) database during July 2015-June 2021. Disproportionality analyses were performed using reporting odds ratios (RORs) to detect AE signals of alirocumab and evolocumab in the overall population and in different age and gender subgroups, respectively.Results: Compared with all other drugs, both alirocumab and evolocumab had a significant signal in “musculoskeletal and connective tissue disorders” (ROR1 = 2.626, 95% CI 2.552–2.702; ROR2 = 2.575, 95% CI 2.538–2.613). The highest ROR value of 2.311 (95% CI 2.272–2.351) was for “injury, poisoning and procedural complications” and was found in patients aged ≥65 years on evolocumab. The most frequent AEs were “general disorders and administration site conditions” and “musculoskeletal and connective tissue disorders” for all subpopulations. At the preferred term level, the most frequent AE signal was myalgia for alirocumab and injection site pain for evolocumab, overall and by subgroups. Compared with statins/ezetimibe, PCSK9 inhibitors exhibited lower ROR values for adverse events associated with SOC “nervous system disorders”, “psychiatric disorders” and “metabolism and nutrition disorders” (all RORs < 1), but mixed results for musculoskeletal disorders. Compared with all other drugs, undocumented AEs, such as acute cardiac event (ROR = 30.0, 95% CI 9.4–95.3) and xanthoma (ROR = 9.3, 95% CI 3.4–25.5), were also reported.Conclusion: Real-world evidence showed that PCSK9 inhibitors were associated with an increased risk of musculoskeletal and connective tissue disorders and general disorders and administration site conditions, overall and by subgroups. Muscle toxicity, injection site reactions, and influenza-like illness were significant AE signals. Compared with various statins and ezetimibe, PCSK9 inhibitors have shown a favorable safety profile in muscle-related events, cognitive impairment and diabetes. Some undocumented AE signals were also reported. Due to the limitations of spontaneous reporting databases, further studies are still needed to establish causality and validate our results.

Background Individuals with diabetes have increased risk of depression, but there are limited nationally representative studies on this topic. We aimed to investigate the prevalence and predictors of depression, as well as its impact on all-cause and cardiovascular mortality in adults with type 2 diabetes (T2DM) using a prospective cohort study and a representative sample of the U.S. population. Methods We analyzed National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018 and linked it with the most recent publicly available National Death Index (NDI) data. Individuals aged 20 years or old who had depression measurements were included. Depression was defined as a Patient Health Questionnaire (PHQ-9) score ≥ 10, and categorized into moderate (10–14 points) and moderately severe to severe (≥ 15 points). Cox proportional hazard models were used to estimate the association between depression and mortality. Results Among 5695 participants with T2DM, 11.6% had depression. Depression was associated with female gender, younger age, overweight, lower education, being unmarried, smoking, and a history of coronary heart disease and stroke. During a mean follow-up period of 78.2 months, 1161 all-cause deaths occurred. Total depression and moderately severe to severe depression significantly increased all-cause mortality (adjusted hazard ratio [aHR] 1.36, 95% CI [1.09–1.70]; 1.67 [1.19–2.34]) and non-cardiovascular mortality (aHR 1.36, 95% CI [1.04–1.78]; 1.78, 95% CI [1.20–2.64]), but not cardiovascular mortality. Subgroup analysis showed a significant association between total depression and all-cause mortality in males (aHR 1.46, 95% CI [1.08–1.98]) and those aged 60 years or older (aHR 1.35, 95% CI [1.02–1.78]). Any severity of depression was not significantly associated with cardiovascular mortality in age- or gender- stratified subgroups. Conclusions In a nationally representative sample of U.S. adults with T2DM, approximately 10% experienced depression. Depression did not significantly associate with cardiovascular mortality. However, comorbid depression in T2DM patients increased the risk of all-cause and non-cardiovascular mortality. The impact of depression on mortality varied across subgroups. Therefore, healthcare providers should consider incorporating depression screening and management into routine care, especially for subgroups with specific risk factors, due to the increased risk of all-cause mortality in T2DM patients with depression.

ObjectivesTo assess the contemporary prevalence and decadal trends of depression and antidepressant use among adults with cardiovascular disease (CVD) in the United States, as well as their risk factors from 2009 to 2020.Materials and methodsWe used the National Health and Nutrition Examination Survey data to calculate the weighted prevalence of depression and antidepressant use. Adults aged 20 years or older with CVD were included. Depression and CVD were assessed by the Patient Health Questionnaire (PHQ-9) and self-report, respectively.ResultsA total of 3,073 eligible participants with CVD aged >20 years were included. The overall prevalence of depression defined by PHQ-9 score ≥10 was 15.7% (95% CI 13.8–17.5), with a steady trend during 2009–March 2020 (p = 0.777). Female gender (aOR 1.78, 95% CI 1.20–2.64) and sleep disorder (aOR 2.62, 95% CI 1.78–3.86) were independent risk factors for depression in CVD patients, while high education level, high income, longer sleep duration, and non-current smokers were considered protective factors. The weighted prevalence of antidepressant use among depressed patients with CVD was 38.6%, which also remained unchanged during the survey period (p = 0.699). Participants with normal sleep pattern and duration were significantly less likely to take antidepressants (p = 0.003).ConclusionThe longitudinal trends in the prevalence of depression among CVD patients in the United States have been stable over the past decade, despite being significantly higher in women, and those with sleep disorders. Overall, antidepressant use was fairly low. Aggressive screening and tailored treatment are recommended for specific vulnerable subpopulations to improve their clinical outcomes.

Introduction: Oral semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that improves glycated hemoglobin levels and body weight in patients with type 2 diabetes (T2DM). We aim to evaluate the cost-effectiveness of once-daily oral semaglutide in comparison to placebo and injectable GLP-1 RAs in Chinese patients with T2DM inadequately controlled on basal insulin.Methods: The United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS OM2.1) was used to estimate the cost-effectiveness by calculating the incremental cost-effectiveness ratio (ICER). Baseline characteristics of the simulation cohort were obtained from the PIONEER 8 trial. Utility and safety inputs were derived from a network meta-analysis of 12 trials. Direct medical costs were retrieved from published literature and discounted at an annual rate of 5%. We used a willingness-to-pay (WTP) threshold of $36,528.3 per quality-adjusted life-year (QALY) gained. Scenario analysis, and one-way and probabilistic sensitivity analysis were performed.Results: The effectiveness of oral semaglutide was 10.39 QALYs with a total cost of $30,223.10, while placebo provided 10.13 QALYs at a lower total cost of $20,039.19. Oral semaglutide was not cost-effective at an ICER of $39,853.22 and $88,776.61 per QALY compared to placebo and exenatide at the WTP. However, at an annual price of $1,871.9, it was cost-effective compared with dulaglutide, liraglutide, and lixisenatide. The model was most sensitive to the discount rate and annual cost of oral semaglutide. The price of oral semaglutide needed to be reduced to $1,711.03 per year to be cost-effective compared to placebo and other injectable GLP-1 RAs except for exenatide and semaglutide injection.Conclusion: We found that once-daily oral semaglutide, at a comparable price of semaglutide injection, proves to be a cost-effective add-on therapy to insulin for Chinese patients with T2DM, especially when compared to subcutaneous GLP-1 RAs other than injectable semaglutide and exenatide. However, to achieve cost-effectiveness in comparison to placebo, further cost reduction of oral semaglutide is necessary. The estimated annual cost of $1,711.03 for oral semaglutide demonstrates a more cost-effective option than placebo, highlighting its potential value in the management of T2DM.