A pilot project implementing a team-based approach for remote physiologic monitoring in an accountable care organization.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Discontinuing semaglutide after weight loss: strategy for weight maintenance and a possible new side effect.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) facilitate weight loss. Weight regain off therapy is concerning. We reported the case of a 35-year-old male prescribed oral semaglutide with 22.7 kg weight loss over 120 days. Herein, we describe the clinical course when discontinuing GLP-1 RA therapy, one approach to maintaining weight loss after discontinuation, and a possible new side effect. At day 120, we continued oral semaglutide 7 mg daily, down from 14 mg, for weight maintenance with subsequent weight regain. We re-increased semaglutide to 14 mg/day with weight re-loss within 1 month and weight maintance for a year. We then discontinued semaglutide; weight loss was maintained for 6 months. The patient reported lactose intolerance ∼13 months before starting semaglutide. During semaglutide therapy, the patient reported worsened lactose intolerance and new gluten intolerance. Food allergy/celiac testing were negative. Intolerances did not improve with semaglutide discontinuation. Six months after semaglutide discontinuation, the patient was diagnosed with small intestinal bacterial overgrowth, possibly worsened by semaglutide. Factors potentially supporting weight maintenance were early drug treatment for new-onset obesity, non-geriatric age, strength training, and diet modification. The case highlights tailoring approaches to maintain weight loss without GLP-1 RAs. Trials are needed to optimize weight maintenance strategies.

Association of Common Foods with Inflammation and Mortality: Analysis from a Large Prospective Cohort Study.

Some dietary patterns are associated with inflammation, while others lower inflammation and improve health. However, many people cannot follow a complete, healthy diet. Therefore, this study's aim was to identify specific foods associated chronic inflammation and mortality. The study used Multi-Ethnic Study of Atherosclerosis (MESA) research materials from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center. Three plant-based and three animal-based MESA food categories were chosen based on perceived availability in the western diet. The assessed food categories were avocado, ham, sausage, eggs, greens, and broccoli. Inflammatory markers assessed were interleukin-6 (IL-6), fibrinogen antigen, C-reactive protein, D-Dimer, interleukin-2, matrix metalloproteinase 3, necrosis factor-a soluble receptors, oxidized LDL (oxLDL), and total homocysteine. The primary outcome was the multivariable association of foods and inflammatory markers with all-cause mortality. All inflammatory makers, except oxLDL, were associated with mortality in univariate analysis. The effect was largest with IL-6 and D-dimer. The category of broccoli had the most consistent association in univariate analyses with lower inflammation and lower mortality odds. Low and high broccoli consumption versus no consumption were associated with lower mortality odds in the multivariable models with IL-6 and D-dimer. Consumption of the MESA-defined food category "broccoli" (i.e., broccoli, cabbage, cauliflower, brussels sprouts, sauerkraut, and kimchee) was associated with lower inflammation and lower mortality odds. These findings should be validated in randomized controlled trials testing a "food is medicine" approach to identify which, if any, of these foods may have potential as an herbal therapeutic for chronic inflammation.

A Review of the Safety and Efficacy of Bexagliflozin for the Management of Type 2 Diabetes.

OBJECTIVE: To review the pharmacology of bexagliflozin in addition to its safety and efficacy from available clinical trials used for its approval, as well as available clinical evidence to date. DATA SOURCES: A search of the National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov) and PubMed database was performed from inception through June 1, 2023. STUDY SELECTION AND DATA EXTRACTION QUANTIFICATION: The following study designs were included: meta-analyses, systematic review, clinical trial, or observational study design. Abstracts and drug monographs were also reviewed. Narrative or scoping reviews were excluded. Only articles in the English language and those evaluating the pharmacology, pharmacokinetics, safety, or efficacy of bexaglifozin in humans were included. DATA SYNTHESIS: Bexagliflozin reduces hemoglobin A1c ~0.5% with similar reductions in systolic blood pressure and body weight to other SGLT2 inhibitors. No cardiovascular outcomes trial is published, nor ongoing at this time. Adverse effects are similar to other SGLT2 inhibitors (genital mycotic and urinary tract infections, increased urination) including a warning for lower extremity amputation similar to canagliflozin. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Although no cost-effectiveness data are available, statements from the manufacturer suggest a competitive price point. Given limited trial data, lower cost, if chosen, may create a temporary niche for bexagliflozin pending generic availability of other SGLT2 inhibitors. However, given lack of cardiovascular and renal outcome data, empagliflozin, dapagliflozin, or canagliflozin may be preferred. CONCLUSION: Bexagliflozin appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2D.

A Systematic Approach to Treating Early Metabolic Disease and Prediabetes.

At least 70% of US adults have metabolic disease. However, less is done to address early disease (e.g., overweight, obesity, prediabetes) versus advanced disease (e.g., type 2 diabetes mellitus, coronary artery disease). Given the burden of advanced metabolic disease and the burgeoning pandemics of obesity and prediabetes a systematic response is required. To accomplish this, we offer several recommendations: (A) Patients with overweight, obesity, and/or prediabetes must be consistently diagnosed with these conditions in medical records to enable population health initiatives. (B) Patients with early metabolic disease should be offered in-person or virtual lifestyle interventions commensurate with the findings of the Diabetes Prevention Program. (C) Patients unable to participate in or otherwise failing lifestyle intervention must be screened to assess if they require pharmacotherapy. (D) Patients not indicated for, refusing, or failing pharmacotherapy must be screened to assess if they need bariatric surgery. (E) Regardless of treatment approach or lack of treatment, patients must be consistently screened for the progression of early metabolic disease to advanced disease to enable early control. Progression of metabolic disease from an overweight yet otherwise healthy person includes the development of prediabetes, obesity ± prediabetes, dyslipidemia, hypertension, type 2 diabetes, chronic kidney disease, coronary artery disease, and heart failure. Systematic approaches in health systems must be deployed with clear protocols and supported by streamlined technologies to manage their population's metabolic health from early through advanced metabolic disease. Additional research is needed to identify and validate optimal system-level interventions. Future research needs to identify strategies to roll out systematic interventions for the treatment of early metabolic disease and to improve the metabolic health among the progressively younger patients being impacted by obesity and diabetes.

Pharmacist-driven continuous glucose monitoring in community and ambulatory care pharmacy practice: A scoping review.

BACKGROUND: Continuous glucose monitoring (CGM) devices improve clinical outcomes and facilitate achieving patient-specific goals. However, opportunities and barriers to implementation of pharmacist-driven CGM services are not well-described. OBJECTIVES: This scoping review was conducted to identify opportunities and barriers to implementing pharmacist-driven CGM services in the community and ambulatory care setting. Clinical outcomes resulting from pharmacist-driven CGM were also explored. METHODS: A health librarian searched Ovid MEDLINE, Cochrane CENTRAL, Embase, Web of Science, Scopus, International Pharmaceutical Abstracts using keywords and subject headings from inception through December 2, 2022 to identify studies describing pharmacist or pharmacy-based CGM programs. No publication type, date limits, language restrictions, or other filters were applied. The database search was supplemented by a search of Google Scholar and a citation search of preselected gold standard articles. RESULTS: The scoping review initially identified 942 citations of which 249 passed abstract screening and 11 were included in the review. Among studies, the most common design was retrospective, populations varied, control groups were not consistently used, follow-up was primarily short, and sample sizes were small. One study evaluated pharmacist-driven CGM in a community pharmacy setting. Ten studies took place in the ambulatory care setting. Barriers to initiating pharmacist-driven CGM as a clinical service include educational, logistical, workflow, and financial incentive. Beneficial outcomes from pharmacist-driven CGM include improved quality of life, increased empowerment, and improved glycemic control. CONCLUSION: There is lack of strong evidence to support pharmacist-driven CGM in the community pharmacy setting. However, small studies suggest pharmacist-driven CGM is feasible and beneficial in the ambulatory care setting. Further exploration of how educational, logistical, workflow, and financial barriers can be overcome is warranted, given potential for improved clinical outcomes.

Inclisiran for the Treatment of Hyperlipidemia and for Atherosclerotic Cardiovascular Disease Risk Reduction: A Narrative Review.

PURPOSE: Inclisiran is a novel nonstatin therapy providing significant reduction in low-density lipoprotein cholesterol (LDL-C) as well as improvements in other lipid biomarkers. This review summarizes data from postapproval publications regarding the impact of inclisiran on lipids and cardiovascular risk reduction, as well as its tolerability and cost-effectiveness. METHODS: A search of PubMed for inclisiran was used to identify articles published since its approval by the US Food and Drug Administration (FDA). Clinical research studies reporting meta-analysis; pooled patient-level trial analyses; cost-effectiveness analyses; new human data; prespecified, post-hoc, or subgroup trial analyses; and clinical trial extensions were included. FINDINGS: The search identified 153 citations; 16 studies were included. FDA-approval trials, subsequent pooled patient-level trial analyses, and extension studies found that inclisiran, administered with and without maximally tolerated statin therapy, reduced LDL-C by ≈50%, with the reduction sustained for 4 years. Inclisiran appeared to be well tolerated, even long-term, with injection-site reactions being the most common adverse effect. A patient-level pooled analysis of data from Phase III trials suggested that cardiovascular events were reduced with inclisiran versus placebo (7.1% vs 9.4%; odds ratio = 0.74 [95% CI, 0.58-0.94]). Inclisiran is suggested to be cost-effective based the presumed cardiovascular benefit commensurate with LDL-C reduction. IMPLICATIONS: The cardiovascular benefit and cost-effectiveness of inclisiran are promising, though not definitive. The results of a large-scale study of the effects of inclisiran on cardiovascular outcomes are expected in 2026; until then, the nonstatin therapies primarily prescribed for LDL-C reduction remain proprotein convertase subtilisin/kexin (PCSK)-9 inhibitors and ezetimibe. However, inclisiran is a reasonable alternative to, PCSK-9 inhibitors, in patients who struggle with the self-injection of or adherence to PCSK-9 inhibitors as inclisiran maintenance therapy is administered twice yearly by a health care professional.

Impact of Overbasalization on Clinical Outcomes in Patients With Type 2 Diabetes: A Post Hoc Analysis of a Large Randomized Controlled Trial.

The American Diabetes Association's Standards of Medical Care in Diabetes emphasize the need for awareness regarding overbasalization (basal insulin doses >0.5 units/kg/day without bolus insulin) in the treatment of type 2 diabetes. However, outcomes data on the impact of overbasalization are limited. This post hoc analysis of a large randomized controlled trial suggests that an insulin therapy regimen involving overbasalization compared with a basal-bolus insulin regimen that avoids overbasalization is less effective at lowering A1C and may be associated with increased cardiovascular risk. Clinicians should consider alternative approaches to glycemic control before increasing basal insulin doses to >0.5 units/kg/day.

Use and Interchange of Incretin Mimetics in the Treatment of Metabolic Diseases: A Narrative Review.

PURPOSE: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and now tirzepatide, a dual GLP-1 RA/glucose-dependent insulinotropic polypeptide agonist, have numerous advantages in the treatment of type 2 diabetes and obesity, yet only 11% of patients with type 2 diabetes are prescribed a GLP-1 RA. This narrative review addresses the complexity and cost issues surrounding incretin mimetics to support clinicians. METHODS: This narrative review summarizes key trials on the differing effects of incretin mimetics on glycosylated hemoglobin and weight, provides a table with rationale for how to interchange among agents, and summarizes the key factors that guide drug selection beyond guidance from the American Diabetes Association. To support proposed dose interchanges, we preferentially selected high-quality, prospective randomized controlled trials with direct comparisons of agents and doses when available. FINDINGS: Tirzepatide produces the greatest reductions in glycosylated hemoglobin and weight, but its impact on cardiovascular events is still under investigation. Subcutaneous semaglutide and liraglutide are approved for weight loss specifically and are effective in the secondary prevention of cardiovascular disease. Although producing less weight loss, only dulaglutide has effectiveness in the primary and secondary prevention of cardiovascular disease. Semaglutide is the only orally available incretin mimetic; however, the oral formulation produces less weight loss versus its subcutaneous alternative and did not have cardioprotection in its outcomes trial. Although effective in controlling type 2 diabetes, exenatide extended release has the least impact on glycosylated hemoglobin and weight among commonly used agents, while not having cardioprotection. However, exenatide extended release may be preferred on some restrictive insurance formularies. IMPLICATIONS: Although trials have not explicitly studied how to interchange among agents, interchanges can be guided by comparisons between agents' impact on glycosylated hemoglobin and weight. Efficient changes among agents can help clinicians optimize patient-centered care, particularly in the face of changing patient needs and preferences, insurance formularies, and drug shortages.

Vancomycin Flight Simulator: A Team-Based Learning Exercise.

BACKGROUND: Team-based learning (TBL) encourages learners to think critically to solve problems they will face in practice. Pharmacokinetic dosing and monitoring are complex skills requiring the application of learned knowledge. The study sought to assess the impact of a TBL, vancomycin dosing activity in a Pharmaceutical Skills IV course measured with exam question performance during the second professional year. METHODS: This retrospective, descriptive study relates a TBL activity, assigned to 85 students, which included an individual student pre-preparation quiz, assigned readings, in-class individual and team-based readiness assessments, small group application of a vancomycin patient case, and group discussion/feedback on clinical decisions with supportive reasoning. The class year before and class year of the TBL implementation were compared using the total percentage of points possible earned by the class years, by topic. To minimize potential confounding, the primary outcome was the change in topic performance by the rank difficulty (e.g., the largest possible benefit being the hardest topic becoming the easiest with no other variation in topic rank difficulty). RESULTS: In the year of implementation, the mean individual readiness assurance test (IRAT) performance was 5.5 ± 1.88 (10 points possible, 55%). The mean team readiness assurance test (TRAT) performance was 10 of 10 points possible (100%). The class exam item performance in the year before (n = 101) and year of (n = 84) TBL implementation showed a general decline in exam scores. However, the vancomycin topic difficultly went from fifth easiest, to second easiest, with less than 1% change in raw score. CONCLUSIONS: Implementation of a pharmacokinetic TBL activity appeared to moderately support the students' vancomycin learning. Additional studies are warranted on APPE readiness and performance.

Effect of Antidepressants on Glucagon-Like Peptide-1 Receptor Agonist-Related Weight Loss.

Background: Depression and obesity have a bidirectional relationship making the management of one, without the other, problematic. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a preferred medication class for diabetes and obesity treatment given their weight loss effect; however, it is not known how antidepressants impact this effect. Objective: To assess the impact of antidepressant use on GLP-1 RA-associated weight loss in patients with or without type 2 diabetes mellitus. Methods: This was a retrospective, propensity matched, cohort study conducted using TriNetX. The study identified patients initiating a GLP-1 RA being treated with citalopram/escitalopram, bupropion, or no antidepressant. Cohorts were propensity score matched to analyze the primary outcome of mean end-of-study (77-371 days) body weight. Results: An initial query identified 31 273 patients eligible for analysis (30 160 receiving no antidepressant, 311 receiving bupropion, and 802 receiving citalopram/escitalopram). After propensity score matching, the study found patients receiving citalopram/escitalopram were taking more antidiabetic therapies at baseline compared with patients not treated with an antidepressant. Patients in the antidepressant cohorts experienced less weight loss compared with their respective matched cohorts not receiving antidepressants (citalopram/escitalopram -0.73 kg versus -1.74 kg; bupropion -0.84 kg versus -3.46 kg). Only the bupropion cohort was significantly heavier at end-of-study versus the non-antidepressant cohort (108 kg versus 103 kg, P = 0.018). Conclusion and Relevance: Antidepressants may diminish the weight loss effect of GLP-1 RAs. Additional research is needed to assess whether all GLP-1 RAs are affected similarly and the optimal weight loss strategies in patients receiving antidiabetic therapy with comorbid depression.

Novel biomarkers of inflammation in heart failure with preserved ejection fraction: analysis from a large prospective cohort study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous cluster of causes, including non-resolving inflammation, endothelial dysfunction, and multi-organ defects. The present study's objective was to identify novel predictors of HFpEF. METHODS: The study analyzed the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the association of specific markers of inflammation with new onset of HFpEF (interleukin-2 [IL-2], matrix metalloproteinase 3 [MMP3], large low-density lipoprotein cholesterol [LDL-C], and medium high-density lipoprotein cholesterol [HDL-C]). The study included men and women 45 to 84 years of age without cardiovascular disease at baseline. The primary outcome was the multivariate association of the hypothesized markers of inflammation with new-onset of HFpEF versus participants without new-onset heart failure. Participants with missing data were excluded. RESULTS: The present analysis included 6814 participants, 53% female, with a mean age of 62 years. Among the entire cohort, HFpEF was diagnosed in 151 (2.2%) participants and heart failure with reduced ejection fraction (HFrEF) was diagnosed in 146 (2.1%) participants. Participants were followed for the outcome of heart failure for a median 13.9 years. Baseline IL-2 was available for 2861 participants. The multivariate analysis included 2792 participants. Of these, 2668 did not develop heart failure, 62 developed HFpEF, 47 developed HFrEF, and 15 developed unclassified heart failure. In the multivariate regression model, IL-2 was associated with new-onset HFpEF (OR, 1.00058; 95% confidence interval, 1.00014 to 1.00102, p = 0.009) but not new-onset HFrEF. In multivariate analysis, MMP3, large LDL-C, and medium HDL-C were not associated with HFpEF or HFrEF. CONCLUSION: These findings portend IL-2 as an important component of suboptimal inflammation in the pathogenesis of HFpEF.

Is it Time to Expand Glucagon-like Peptide-1 Receptor Agonist Use for Weight Loss in Patients Without Diabetes?

The obesity and type 2 diabetes mellitus epidemics demonstrate that simply emphasizing a healthy lifestyle is insufficient. While weight loss medications have historically been considered "cosmetic", glucagon-like peptide-1 receptor agonists (GLP1-RAs) also reduce cardiovascular risk in patients with type 2 diabetes. Therefore, we assessed whether GLP1-RAs warrant use in patients who are overweight (body mass index 27.0-29.9 kg/m2) without weight-related comorbidity. We reviewed trials of available GLP1-RAs with a natural GLP1 backbone given their trend toward cardiovascular benefit and excluded trials requiring concurrent antidiabetic agents associated with weight gain. We assessed 20 phase III trials of GLP1-RAs studied in cardiovascular outcome trials. The GLP1-RAs consistently produced weight loss. Hypoglycemia risk with GLP1-RAs was generally low without other precipitating factors, whereas gastrointestinal adverse effects were common. Dulaglutide 1.5 mg weekly did not produce sufficient weight loss to support its use specifically for weight loss, while data supporting dulaglutide 3.0 or 4.5 mg weekly were limited to a single trial. Weight loss was sufficient with liraglutide 1.8 mg daily in one trial and was consistently sufficient with liraglutide 3.0 mg daily. Oral and injectable semaglutide at both doses consistently produced weight loss, though demonstrated a potential increased risk for retinopathy. Overall, we suggest five GLP1-RAs can be used in the treatment of overweight (body mass index 27.0-29.9 kg/m2 without weight-related comorbidity) with shared decision making to address each medications' key limitation: liraglutide 1.8 mg daily (less demonstrated weight loss), liraglutide 3.0 mg daily (no cardiovascular outcome trial at this dose), and oral and injectable semaglutide at both doses (uncertain retinopathy risk and pending cardiovascular outcome trial of high-dose semaglutide). Use should be limited to patients who fail, refuse, or cannot access lifestyle interventions for weight loss, and should be accompanied by standard restrictions on and monitoring of weight loss medications. We expect additional and earlier use of weight loss therapies to help clinicians curb the obesity and type 2 diabetes epidemics.