Budget impact analysis for three glucagon-like peptide-1 receptor agonist-based therapies for type 2 diabetes mellitus management in Saudi Arabia.

BACKGROUND AND OBJECTIVES: This study presents a budget impact analysis (BIA) conducted in Saudi Arabia, evaluating the cost implications of adopting semaglutide, tirzepatide, or dulaglutide in the management of type 2 diabetes mellitus (T2DM) patients. The analysis aims to assess the individual budgetary impact of these treatment options on healthcare budgets and provide insights for decision-makers. METHODS: A prevalence-based BIA was developed using real-world and clinical trials data. The model considered disease epidemiology, medication prices, diabetes management expenses, cardiovascular (CV) complications costs, and weight reduction savings over a 5-year time horizon. One-way and probabilistic sensitivity analyses (OWSA, PSA) were performed to assess the robustness of the results. RESULTS: Over a 5-year period, the cumulative budget impact for semaglutide, tirzepatide, and dulaglutide were 85,923,089 USD, 169,790,195 USD, and 94,558,356 USD, respectively. Hypothetical scenarios considering price parity between semaglutide and tirzepatide are associated with financial impacts of 85,923,091 USD and 86,475,335 USD, respectively. In the public sector, semaglutide showed the lowest incidence of 3-point major adverse CV events (3P-MACE), with tirzepatide leading in weight loss and HbA1c reduction, and dulaglutide presenting the highest 3P-MACE rates and least improvements in HbA1c and weight. A breakeven analysis suggested that tirzepatide's list price would need to be $199.91 lower than its current list price to achieve budget impact parity with semaglutide based on currently available evidence. Results from the OWSA suggested that risk reductions for CV events were key drivers of budget impact. PSA results were confirmatory of base-case analyses. CONCLUSIONS: CV cost-offsets and drug acquisition considerations may make semaglutide a favorable use of resources for Saudi budget planners and decision-makers. These results were robust to assumptions regarding the list price of tirzepatide.

Improvement of comorbid anxiety and depression in patients with migraine treated with injectable preventive calcitonin gene-related peptide antagonists: Review of clinical evidence.

Background: Migraine is often associated with depression and anxiety, leading to a diminished quality of life. Calcitonin gene-related peptide (CGRP) antagonists have shown promise in treating migraines, but their effects on concurrent depression and anxiety have not been clarified. Methods: A literature review was conducted on ClinicalTrials.gov, PubMed, Ovid Medline, and EMBASE focusing on phase 3 clinical trials, post-hoc analysis studies, and real-world evidence (RWE) published in the past 5 years. The review primarily utilized patient-reported outcome tools, such as the Patient Health Questionnaire-9, Hamilton Depression Rating Scale, Beck Depression Inventory-II, generalized anxiety disorder (GAD)-7, and Hamilton Anxiety Rating Scale (HARS), to assess anxiety and depression in relation to CGRP-targeted monoclonal antibodies. Results: Out of 260 studies, 17 met the inclusion criteria. Eptinezumab lacked sufficient evidence regarding its impact on depression and anxiety. While sufficient evidence on its effect on comorbid anxiety was not available, fremanezumab was shown to significantly improve comorbid depression in one study while not achieving statistical significance in another. Erenumab and galcanezumab showed significant improvement in comorbid depression, implying possible benefits in patients with migraine. Galcanezumab showed faster relief from depressive symptoms than other injectable CGRP antagonists. Galcanezumab also exhibited improvements in GAD-7 scores for anxiety, although not statistically significant, whereas RWE showed promising HARS scores for both galcanezumab and erenumab. Conclusions: Galcanezumab and erenumab appear to be more effective in improving concurrent depressive and anxiety symptoms in migraine patients than fremanezumab. Notably, these psychometric questionnaires were not the primary outcome measures of the trials and were not specifically designed to investigate the effects of these medications on depression or anxiety. Further research is needed to fully understand the impact of CGRP antagonists on mental health disorders associated with migraines. These findings have implications for enhancing the overall well-being and quality of life in individuals with migraines and comorbid psychiatric conditions.

Early Versus Late Initiation of Hydrocortisone in Patients With Septic Shock: A Prospective Study.

Introduction The optimal timing of corticosteroid initiation in septic shock patients is debatable. The Surviving Sepsis Campaign Guidelines recommended adding hydrocortisone to septic shock patients who require a vasopressor with a dose of norepinephrine ≥ 0.25 mcg/kg/min for at least four hours. Nevertheless, the best time to initiate hydrocortisone remains uncertain. Objective Assessing the impact of early (≤3 hours) versus late (>3 hours) initiation of hydrocortisone in septic patients. Methodology We compared the outcomes of septic shock patients who received hydrocortisone within three hours versus those who started treatment after three hours. The inclusion criteria encompassed septic shock patients aged 18 or older who received at least one dose of hydrocortisone. Exclusion criteria included pregnancy, do-not-resuscitate orders, the absence of empirical intravenous antibiotics, recent corticosteroid use, recent cardiac arrest, and a history of adrenal insufficiency. Results Eighty-one patients were included (54% were males). The mean age was 59 years, and 56.8% of patients were in the early group. The time needed to discontinue vasopressors was 25 and 37 hours for the early and late groups, respectively (p = 0.009), and more patients achieved reversal of shock (35 vs. 24 patients) and had shorter ICU stays (17 days vs. 20 days). Conclusion Initiating hydrocortisone early, within three hours, reduced the time needed to discontinue vasopressors among the study population. However, both early and late initiation strategies yielded comparable outcomes in terms of ICU mortality, ICU length of stay, and shock reversal.

Retracted: Calcitonin Gene-Related Peptide (CGRP) Antagonists: A comprehensive review of safety, efficacy and prescribing information.

WHAT IS KNOWN AND OBJECTIVES: Migraine is a disabling disorder that affects individuals of all ages. To date, there are multiple limitations to using guidelines-recommended treatments and preventive therapies. The goal of this review was to provide a comprehensive clinical review of the safety, efficacy and prescribing information of the emerging calcitonin gene-related peptide (CGRP) antagonists. Agents in this new pharmacologic class were approved by the US Food and Drug Administration (FDA) for the treatment of acute migraine attack pain and the management of episodic and chronic migraine. METHODS: A total of 12 randomized, placebo-controlled clinical trials were identified and included in the review utilizing databases such as clinicaltrial.gov, PubMed and EMBASE. The trials collectively evaluated six CGRP antagonists starting from the orally administered CGRPs such as rimegepant and ubrogepant, to the quarterly IV administered CGRP such as eptinezumab, and the monthly/quarterly subcutaneously administered agents such as erenumab, fremanezumab and galcanezumab. RESULTS AND DISCUSSION: All agents displayed significant efficacy compared with placebo, measured by reduction in mean monthly migraine days (MMD). In addition, CGRP antagonists displayed a great tolerability profile with few adverse effects. These medications were neither associated with any cardiovascular-related adverse effects, nor do they currently have specific contraindications to pre-existing cardiovascular conditions. This can present a safe alternative to a wide range of patients who cannot be appropriately treated with first-line treatments such as triptans. No treatment-related death was reported in any of the clinical trials outlined and discussed. WHAT IS NEW AND CONCLUSION: Calcitonin gene-related peptide antagonists are safe and efficacious medications both in treating acute migraine headache pain and the management of episodic and chronic migraine. Head-to-head comparative studies with current guideline-recommended treatments are needed. However, CGRP antagonists are promising agents that present an alternative solution for patients living with migraine.