Beyond glycemia: Comparing tirzepatide to GLP-1 analogues.

Glucagon-like peptide-1 receptor analogs (GLP-1 RAs) have been an innovative and instrumental drug class in the management of both type 2 diabetes and obesity. Tirzepatide is a novel agent that acts as an agonist for both GLP-1 receptors and gastric inhibitory polypeptide (GIP) receptors, another incretin that lowers glucose and appetite. Although previous studies showed a lack of therapeutic benefit for GIP agonists, current studies show that the glucose lowering and weight loss effects of tirzepatide are at least as effective as GLP-1 RAs with a similar adverse effect profile. Some studies, though not conclusive, predict that tirzepatide may in fact be more potent than GLP-1 RAs at reducing weight. A thorough review of the studies that led to tirzepatide's approval allows for comparisons between tirzepatide and GLP-1 RAs; it also allows for predictions of tirzepatide's eventual place in therapy - an agent used preferentially over GLP-1 RAs in patients with or without diabetes desiring to lose weight.

Physician and Pharmacist: Attitudes, Facilitators, and Barriers to Prescribing Naloxone for Home Rescue.

BACKGROUND AND OBJECTIVES: We implemented a naloxone education and distribution program in our academic health system. Despite the program, naloxone prescribing was not fully realized. This study aimed to identify the barriers to prescribing. METHODS: We conducted a prospective, cross-sectional, mixed-methods study of naloxone prescribers. Participants completed a questionnaire regarding their prescribing practices, attitudes, facilitators, and barriers to prescribing naloxone. Participants were then invited for an interview to further explore these topics and elicit more in-depth explanations. RESULTS: Sixty-four physicians and eight pharmacists completed the questionnaire (n = 72). The most commonly reported barrier to prescribing naloxone was time constraints (33%). During the interviews, 14 subthemes emerged within four themes: provider competency, provider beliefs, health care system, and patient factors/social climate. DISCUSSION: Prescribers identified barriers to naloxone prescribing despite implementation of an institutional overdose education and naloxone distribution (OEND) program. The results were similar to those previously reported prior to initiation of such programs. CONCLUSION: In this study, we examined barriers and facilitators to naloxone prescribing. Although previous studies have shown that health care providers endorsed similar barriers, our study indicates that some of those barriers persist despite a concerted effort to educate and promote prescribing via an OEND. While our study is limited by a small, selective sample size the results indicate that improvements to our OEND program are warranted. SCIENTIFIC SIGNIFICANCE: Our study addressed an unexplored area of OEND research and may inform future program development. (Am J Addict 2019;00:00-00).

Recent Updates on the Use of PCSK9 Inhibitors in Patients with Atherosclerotic Cardiovascular Disease.

PURPOSE OF REVIEW: Atherosclerotic cardiovascular disease (ASCVD) is caused by elevated levels of low-density lipoprotein cholesterol (LDL-C). Although statins significantly reduce ASCVD risk, there remains a high degree of residual risk in statin-treated patients. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has emerged as a significant therapeutic target for further lowering of LDL-C when used in combination with statins. The purpose of this review is to provide an update on recent evidence supporting the use of PCSK9 inhibitors in patients with ASCVD. RECENT FINDINGS: Alirocumab and evolocumab were approved by the US Food and Drug Administration in 2015. Multiple phase II and III studies have demonstrated that these agents reduce LDL-C levels by up to 60% and are relatively safe, with the exception of injection site reactions. Additionally, two randomized controlled clinical trials have demonstrated that both alirocumab and evolocumab reduce ASCVD events when used in combination with statin therapy compared to statin alone. In light of this evidence, the 2018 Cholesterol Guideline incorporated PCSK9 inhibitors into the treatment algorithm for select secondary prevention patients unable to achieve an LDL-C below 70 mg/dL despite maximally tolerated statin plus ezetimibe. Although PCSK9 inhibitors provide substantial reductions in LDL-C levels and reduce ASCVD events in secondary prevention populations, the cost-effectiveness of alirocumab and evolocumab limit widespread use. Additional research is needed to explore the role of PCSK9 inhibitors in other populations, including primary prevention, patients unable to tolerate statins, and acute myocardial infarction.

Narrative review of data supporting alternate first-line therapies over metformin in type 2 diabetes.

Purpose: Metformin has been the first-line treatment for type 2 diabetes mellitus as monotherapy or concomitantly with other glucose-lowering therapies due to its efficacy, safety, and affordability. Recent studies on the cardioprotective and renoprotective benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have influenced guidelines on diabetes management to consider these newer agents as alternative first-line therapies. This paper explores the literature supporting the use of these newer medications alone as a first-line agent in place of metformin. Methods: A review of citations from the most recent guidelines along with a literature search via PubMed was completed to review (1) what, historically, made metformin first-line (2) if newer agents' benefits remain when used without metformin (3) how newer agents compare against metformin when used without it. Results: Evaluation of the historical literature was completed to summarize the key findings that support metformin as a first-line therapy agent. Additionally, an assessment of the literature reveals that the benefits of these two newer classes are independent of concomitant metformin therapy. Finally, studies have demonstrated that these newer agents can be either non-inferior or sometimes superior to metformin when used as monotherapy. Conclusion: GLP-1 RA and SGLT-2i can be considered as first line monotherapies for select patients with high cardiovascular risks, renal disease, or weight loss requirements. However, pharmacoeconomic considerations along with lesser long-term safety outcomes should limit these agents' use in certain patients as the management of diabetes continues to transition towards shared-decision making. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01406-6.

Adverse childhood experiences among California student pharmacists.

Introduction: Adverse childhood experiences (ACEs) are associated with higher mental and physical illness and substance use disorders in adulthood. However, little is known about the prevalence of ACEs among student pharmacists and the factors associated with exposure. Our objective was to determine the prevalence of ACEs, resilience, and maladaptive coping strategies among student pharmacists in California. Methods: Student pharmacists from 14 California pharmacy schools completed a 24-item online survey in 2020. This survey instrument comprised the ACEs questionnaire and collected data on the students' demographic characteristics, coping strategies, and resilience. Results: Most respondents were Asian/Pacific Islander (n = 186, 61.0%), female (n = 216, 70.8%), and aged between 25 and 31 years (n = 154, 50.7%). Many (n = 137, 44.9%) students had more than 1 ACE exposure; 66 students (21.6%) had more than 3 ACEs. Many students indicated that they were diagnosed or suspected to be diagnosed with a mental health condition (n = 105, 34.4%) and agreed/strongly agreed that they struggled to manage the workload of pharmacy school (n = 119, 39.9%). Respondents with higher ACE scores (> 3) were more likely to report struggling with managing the workload of pharmacy school, have or suspect having a mental health condition, drink alcohol in the last 12 months, and/or have multiple sexual partners than students with lower ACE scores. Discussion: More than 1 in 5 student pharmacists in this study were exposed to more than 3 ACEs. The student pharmacists' ACE exposure was associated with higher likelihood of mental health conditions and high-risk health behaviors. Further studies are needed to investigate this topic among student pharmacists.

Profile of bictegravir/emtricitabine/tenofovir alafenamide fixed dose combination and its potential in the treatment of HIV-1 infection: evidence to date.

Modern pharmacologic management of people living with HIV involves the use of fixed dose combinations of antiretrovirals that are simple to take, well tolerated, and highly effective. Specific recent pharmacologic advancements include 1) the second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) that consistently show less side effects, high tolerability, minimal drug interactions, and rapid rates of HIV viral load decline and 2) tenofovir alafenamide, a prodrug of tenofovir that concentrates in lymphoid tissue and minimizes off target effects. Bictegravir/emtricitabine/tenofovir alafenamide or B/F/TAF is a recently approved fixed dose combination that incorporates these new advancements in the management of HIV. This review focuses on the data supporting the use of B/F/TAF, reviews clinically relevant findings, and highlights the unanswered questions that may limit its clinical utility.

Individualized Pharmacokinetic Dosing of Vancomycin Reduces Time to Therapeutic Trough Concentrations in Critically Ill Patients.

Dosing vancomycin in critically ill patients often results in subtherapeutic and supratherapeutic trough concentrations. In this retrospective study, we compared the time to goal trough attainment and incidence of acute kidney injury in intensive care unit (ICU) patients whose vancomycin was dosed by a pharmacy pharmacokinetic (PK) dosing and monitoring service to the standard of care. Three-hundred fifty adult ICU patients at a Level 1 trauma, teaching hospital who received vancomycin for >24 hours from February 1, 2016, to November 30, 2016, were screened. Patients were included in the PK group if consecutive serum concentrations were used to calculate individualized PK and determine a dosing regimen. Patients who were dosed using troughs only were then matched 1-to-1 to the PK group by date of vancomycin initiation and included in the traditional group. Fifty patients were included in each group. Baseline characteristics were similar, except the PK group had more patients under the care of the neuromedical ICU service (42% vs 18%; P = .02) and fewer patients with a corrected creatinine clearance <30 mL/min/1.73 m2 (22% vs 46%; P = .02). Attainment of goal trough concentrations for the PK and traditional groups were 84.4% and 29.4% by 48 hours (P = .0001), 88.4% and 60.7% by 72 hours (P = .009), and 92.9% and 77.8% by 96 hours (P = .1), respectively. Incidence of acute kidney injury between the PK and traditional groups was not statistically significant (8.3% vs 14%; P = .5). Utilization of individualized pharmacokinetic dosing of vancomycin in critically ill patients resulted in faster goal trough attainment without an increase in nephrotoxicity.