Joel C. Marrs

Dapagliflozin for the Treatment of Type 2 Diabetes

Objective: To review the literature and describe the pharmacologic, pharmacokinetic, and pharmacodynamic properties; clinical safety; and efficacy of dapagliflozin, a new drug currently under review by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes. Data Sources: A MEDLINE (1995-November 2011) and ClinicalTrials.gov search was conducted using the terms dapagliflozin, sodium-glucose cotransporter 2 inhibitor, and SGLT2 inhibitor. Reference citations from publications identified were also reviewed. Study Selection and Data Extraction: All English-language studies, including abstracts, evaluating dapagliflozin use in humans were included in this review. Data Synthesis: Dapagliflozin is the first-in-class oral sodium-glucose cotransporter 2 (SGLT2) inhibitor that represents a new potential therapeutic option for the treatment of type 2 diabetes mellitus. Its mechanism of action is insulin- and insulin-sensitivity independent. Preliminary data suggest that dapagliflozin decreases hemoglobin A1c, fasting plasma glucose, and postprandial plasma glucose, while also promoting weight loss. In Phase 1, 2, and 3 clinical trials, dapagliflozin has exhibited a safety and tolerability profile similar to that of placebo. Conclusions: Dapagliflozin is a novel oral antihyperglycemic agent that has demonstrated promise as monotherapy and as synergistic combination therapy with currently available agents in Phase 3 clinical trials. On January 19, 2012, the FDA issued a complete response letter to AstraZeneca and Bristol-Myers Squibb regarding the new drug application for dapagliflozin. The FDA is requesting additional clinical data—from ongoing studies and potentially new clinical trials—to better describe the risk-benefit profile of the drug. Both manufacturers remain committed to the development of dapagliflozin, and there are currently 8 Phase 3 trials ongoing. Dapagliflozin has the potential to be the next new oral agent in the diabetes drug armamentarium.

Implementation of a Clinical Pharmacy Specialist-Managed Telephonic Hospital Discharge Follow-Up Program in a Patient-Centered Medical Home

The objectives of this retrospective study were to examine the feasibility and characteristics that define successful implementation of a Clinical Pharmacy Specialist (CPS) telephonic hospital discharge follow-up quality improvement initiative, as well as the impact of this initiative. Adult patients who were discharged from a safety-net hospital between July 1, 2010 and June 30, 2011 and who were part of a patient-centered medical home were included in this quality improvement initiative. CPSs attempted to contact 470 patients; of those, 207 received the intervention and 263 did not. Patients in the contacted group were more likely to attend a hospital discharge follow-up appointment (66.2% vs. 44.5%, P<0.01) and had lower rates of 30-day readmission (22 vs. 52, P<0.01) compared to those who were not contacted. Institutions should consider allocating resources for pharmacist-managed posthospital discharge follow-up services because of the potential for positive clinical and financial impact.

Direct Oral Anticoagulants for the Management of Thromboembolic Disorders The Importance of Adherence and Persistence in Achieving Beneficial Outcomes

Anticoagulation therapy is central to the management of thromboembolic disorders, and the use of direct oral anticoagulants offers several advantages over standard therapy with parenteral heparins and vitamin K antagonists. In phase III clinical trials, the direct oral anticoagulants (given once or twice daily) all demonstrated favorable benefit–risk profiles compared with conventional standard therapy for the treatment and secondary prevention of venous thromboembolism and for stroke prevention in patients with nonvalvular atrial fibrillation. In clinical practice, many factors may influence overall clinical outcomes in patients receiving anticoagulant therapy, including adherence and persistence to the prescribed therapy, which becomes particularly important during long-term therapy. When choosing an anticoagulant for an individual patient, the pharmacological and clinical profile of the anticoagulant, its dosing regimen, and the patient’s clinical characteristics (eg, renal function and comorbidities) and preferences should be considered. This review examines the rationale for and clinical evidence of the selected dosing regimens of the direct oral anticoagulants for the treatment of venous thromboembolism and stroke prevention in nonvalvular atrial fibrillation. The potential influence of dosing strategies (eg, once- or twice-daily dosing) and other factors on patient adherence and therapy persistence are also discussed.

Prevalence of and Factors That Influence Board Certification Among Pharmacy Practice Faculty at United States Colleges and Schools of Pharmacy

Board certification is a means of demonstrating expertise above the minimum licensing standards. For many health care professionals, this credential is a necessity. As pharmacists become involved in more advanced patient care services, board certification becomes an essential component to ensuring quality care. The prevalence of United States pharmacy practice faculty members who are board certified, however, is unknown. In addition, to our knowledge, factors that serve to motivate or discourage faculty from obtaining board certification have not been previously described; thus, 900 pharmacy practice faculty members listed in the American Association of Colleges of Pharmacy (AACP) online directory were invited to complete an online survey regarding motivators and barriers for board certification. In addition, a list of board‐certified pharmacists, obtained from the Board of Pharmacy Specialties, was used to check the board certification status of all pharmacy practice faculty members listed in the AACP directory. In 2011, the prevalence of board certification among the 2867 pharmacy practice faculty members was 37% (1063 pharmacists), with the highest prevalence found among assistant professors (39.4%). A total of 322 faculty members (36% response rate) completed the survey; of these, 308 self‐identified as pharmacy practice faculty, and their responses were included in the analysis. Current board certification in pharmacy specialties was reported by 163 respondents (52.9%); 14 (4.5%) were previously certified. Among the 308 respondents, the most common perceived reason why pharmacy practice faculty become board certified was the desire to be recognized as an expert in the field (71.5%). Those who were currently board certified indicated personal growth as the most important reason (60.1%). Those previously certified indicated no perceived benefit as the most common reason for not recertifying (71.4%). Among those never certified, no perceived need (52.0%) or benefit (44.8%) were the most common reasons for not becoming certified; however, a majority of those never certified (68%) stated that they would become board certified if there was no associated cost and they were confident they would pass. To increase the prevalence of board certification in pharmacy practice faculty at U.S. schools and colleges of pharmacy, the benefits of this credential must be addressed at each institution. Steps should be taken to assist and encourage board certification.

Glucose and Low-Density Lipoprotein Cholesterol Lowering in Elderly Patients with Type 2 Diabetes

The prevalence of type 2 diabetes mellitus is high among the elderly population. Treatment of elderly patients with type 2 diabetes presents challenges because of co-morbidities and the potential increase in the risk of adverse effects. Hyperlipidaemia is also common in the elderly population. Glucose-and lipid-lowering treatment in elderly patients should be individualized on the basis of the patient’s life expectancy, health status and cardiovascular risk factors, and evidence-based guideline recommendations. Because elderly patients often have impaired renal and hepatic function, careful considerations must be made when selecting appropriate glucose- and lipid-lowering therapy. There are a number of potential safety issues associated with various glucose- and lipid-lowering therapies that are relevant to elderly patients, including increased risk of heart failure exacerbations, weight loss, increased risk of hypoglycaemia, increased risk of myopathy, and contraindications of some agents in patients with hepatic or renal impairment. The bile acid sequestrant colesevelam HCl is unique compared with other glucose- and lipid-lowering therapies because it is the only product approved by the US Food and Drug Administration, as an adjunct to diet and exercise, to lower both glucose and low-density lipoprotein cholesterol (LDL-C) in adults with type 2 diabetes and primary hyperlipidaemia, respectively. Furthermore, colesevelam has been shown to have similar glucose- and lipid-lowering efficacy in patients aged <65 years and those aged ≥65 years. Colesevelam was not associated with weight gain, was associated with a low incidence of hypoglycaemia, and can be safely combined with a broad range of glucose-lowering agents (metformin, sulfonylureas and insulin) and lipid-lowering statins. Currently, colesevelam is available in tablet form and as a powder for oral suspension formulation; the latter may be of benefit to elderly patients with swallowing difficulties. As colesevelam has both glucose- and lipid-lowering effects, its use may reduce the drug burden in elderly patients receiving multiple agents for glucose and lipid lowering. Colesevelam may be a valuable treatment option as an add-on to existing glucose- and/or lipid-lowering therapy to help improve haemoglobin A1c and to lower LDL-C levels in elderly patients with type 2 diabetes and primary hyperlipidaemia.

Key Articles and Guidelines in the Primary Prevention of Ischemic Stroke

Ischemic stroke is a prevalent disease with a large burden on the health system. Preventive strategies, therefore, are paramount. Primary prevention is aimed at reducing the risk of stroke in asymptomatic people. The most effective prevention is through control of modifiable risk factors. Due to the large amount of literature available on this topic, this bibliography (the first of a 2‐part series) aims to provide a comprehensive resource for medical practitioners charged with caring for this population.

Evaluation of Aspirin Use in Patients With Diabetes Receiving Care in Community Health

Background: The American Diabetes Association (ADA) recommends low-dose aspirin therapy as a primary prevention strategy in patients with type 1 or type 2 diabetes mellitus (DM) at increased cardiovascular risk. However, not all patients who are indicated are taking aspirin therapy, and it is not routinely documented in the electronic health record (EHR). Objective: To determine frequencies of appropriate aspirin use and documentation in the EHR in adult patients with DM. Methods: Adult patients with DM were randomized and contacted for participation in a telephonic survey between January and October 2013. Patients who consented were administered a standardized oral telephone survey regarding aspirin use. Patient demographics, current medications, allergies, past medical history, and pertinent laboratory values were collected. Patients were then stratified by the ADA-defined indication for aspirin. The primary outcomes were rates of appropriate aspirin use and documentation of aspirin therapy in the EHR. Results: Investigators contacted 276 patients for inclusion. Of the 81 patients surveyed, 74% were indicated for aspirin therapy. Nearly all (92.3%) patients reporting aspirin use were indicated for aspirin therapy compared with only 57.1% of patients who did not report aspirin but were indicated (P = 0.0003). Alternatively, 96.7% of patients with aspirin use documented in their EHR were indicated for aspirin therapy compared with only 60.8% of patients who did not have aspirin use documented in the EHR but had an indication (P = 0.0002). Approximately 20% of the patients indicated for and reporting aspirin use did not have aspirin documented in their EHR. Conclusions: Aspirin use in patients with DM who are indicated for therapy is significantly underutilized and underdocumented.

A Review of the Role of the Pharmacist in Heart Failure Transition of Care

This article reviews current literature on the role of pharmacists in the transition of care (TOC) for patients with heart failure (HF) and the impact of their contributions on therapeutic and economic outcomes. Optimizing the TOC for patients with HF from the hospital to the community/home is crucial for improving outcomes and decreasing high rates of hospital readmissions, which are associated with increased morbidity, mortality, and costs. A multidisciplinary team approach to the management of patients with HF facilitates the transition from the hospital to the ambulatory care setting, allowing for the consideration of medical, pharmacological, and lifestyle variables that impact the care of individual patients. Pharmacist participation on both inpatient and outpatient teams can provide a variety of services that have been shown to reduce hospital readmission rates and benefit patient management and treatment. These include medication reconciliation, patient education, medication dosage titration and adjustment, patient monitoring, development of disease management pathways, promotion of medication adherence, and postdischarge follow-up. In addition, as new pharmacologic treatments for HF become available, pharmacists can raise awareness of optimal drug use by maximizing education related to efficacy (e.g., adherence) and safety (e.g., potential side effects and drug interactions). Improving understanding of HF and its treatment will enable increased pharmacist involvement in the TOC that should lead to improved outcomes and reduced healthcare costs.Funding: Novartis.

Antihyperglycemic Medications and Cardiovascular Risk Reduction

Abstract Cardiovascular disease (CVD) remains a leading cause of death in patients with type 2 diabetes (T2D). In addition to glycemic control, a major focus of diabetes treatment involves cardiovascular (CV) risk reduction. In 2008, the US Food and Drug Administration (FDA) instituted a new requirement that new drugs developed and studied for the treatment of T2D must undergo CV safety testing. Since the advent of this new policy, canagliflozin, empagliflozin, liraglutide and semaglutide have demonstrated superior CV event reduction — via a composite of reduction in CV death, nonfatal myocardial infarction (MI), and nonfatal stroke — compared with placebo in patients with T2D and existing CVD, or at high risk of CVD. Multiple studies are underway to evaluate the CV outcomes of other antihyperglycemic agents. In a time when there are numerous drugs in the T2D armamentarium, positive CV outcomes data influence drug selection and aids practitioners in making more individualised therapeutic recommendations for their patients.

Patterns of serum laboratory monitoring for safety and efficacy in patients on chronic statin therapy

Objective: To describe safety and efficacy laboratory monitoring of statin therapy at the University of Colorado Hospital Outpatient Clinics over a period of 3 years prior to the revised United States Food and Drug Administration statin labeling. Methods: This retrospective, observational study evaluated serum laboratory monitoring for safety and efficacy of statin therapy between July 2008 and June 2011. Adult patients prescribed chronic statin therapy were included. The primary objective of this study was to describe the frequency of outpatient liver function tests, lipid panels, and creatine kinase for patients on chronic statin therapy. Results: A total of 143 patients met study criteria. Over a 3-year period, the mean maximum frequency of measurements per patient of serum hepatic transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was higher than lipid panel measurements (5.2 ± 4.4 and 4.2 ± 2.0 respectively, p = 0.021). Only 22 of 143 patients (15.4%) had an elevation in ALT or AST. All elevations were less than three times the upper limit of normal and statin therapy was continued without changes in response to these elevations. Creatine kinase, though not a routine monitoring test, was infrequently measured (mean maximum frequency of measurements per patient 0.3 ± 0.8). Conclusion: Serum hepatic transaminases were routinely monitored in patients treated with chronic statin therapy. Given the absence of significant serum hepatic transaminase elevations, and clinician response to minor elevations, our data indicate that routine serum laboratory evaluations for statin toxicity are excessive.