Philip T. Rodgers

Incretin Mimetics as Emerging Treatments for Type 2 Diabetes

OBJECTIVE: To review the physiology, pharmacology, and clinical efficacy of glucagon-like peptide (GLP-1) and the incretin mimetics exenatide and liraglutide in clinical studies. DATA SOURCES: Primary literature obtained via MEDLINE (1966–April 2004) and International Pharmaceutical Abstracts (1970–April 2004) searches; abstracts obtained from meeting sources and manufacturers. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts evaluating GLP-1, exenatide, and liraglutide in the treatment of patients with type 2 diabetes were reviewed. Data from animal studies were also included if human data were not available. Primary and review articles related to the physiology, development, and evaluation of GLP-1s were reviewed. DATA SYNTHESIS: GLP-1, exenatide (exendin-4, AC2993), and liraglutide (NN2211) are incretin mimetics that have been shown in human studies to be an effective treatment to improve glycemic control in patients with type 2 diabetes. Mechanisms by which these compounds improve glycemic control include enhancing glucose-dependent pancreatic secretion of insulin in response to nutrient intake, inhibiting glucagon secretion, delaying gastric emptying, and promoting early satiety. GLP-1 has been shown to promote pancreatic progenitor cell differentiation and improve β-cell function and lifespan. Reported adverse effects of exenatide and liraglutide include nausea, vomiting, and transient headache, as well as increased risk of hypoglycemia when used with sulfonylureas. CONCLUSIONS: Clinical studies show that GLP-1, exenatide, and liraglutide improve glycemic control for patients with type 2 diabetes through unique mechanisms not available with current pharmaceutical products. Ongoing Phase III studies will help to further position these compounds as treatment options for patients with type 2 diabetes.

Effects of Thiazolidinediones on Bone Loss and Fracture

Objective: To examine the evidence regarding the effects of thiazolidinediones on bone loss and fracture. Data Sources: Published studies assessing the effects of thiazolidinediones on bone and/or fracture risk in humans were selected for review. A MEDLINE (1950–April 2007) and International Pharmaceutical Abstracts (1970–April 2007) search was performed. Search terms included thiazolidinediones, rosiglitazone, pioglltazone, troglitazone, bone, bone mineral density, fracture, and osteoporosis. Study Selection and Data Extraction: The literature search retrieved 5 English-language studies evaluating the effects of thiazolidinediones on bone in humans. These consisted of 2 small, uncontrolled studies using troglitazone; 1 prospective, randomized controlled study and 1 retrospective cohort study using rosiglitazone; and a post hoc analysis of an observational cohort study in subjects taking various thiazolidinediones. All of the studies assessed markers of bone metabolism and/or bone mineral density (BMD). No studies were identified that addressed rate of fractures in subjects taking thiazolidinediones. Data Synthesis: The first troglitazone study demonstrated a decrease in levels of bone formation markers (10%; p<0.05) and resorption markers (12%; p<0.01), and authors determined that troglitazone produces a protective effect on bone through decreased bone turnover. The second troglitazone study did not demonstrate a significant change in BMD or levels of bone turnover markers. The 2 rosiglitazone studies demonstrated decreases in BMD of 1.19–1.9% with rosiglitazone use (p<0.05), The post hoc analysis with various thiazolidinediones indicated a 2.5-fold greater decrease in BMD in women reporting thiazolidinedione use. Conclusions: Few studies have assessed the effects of thiazolidinediones on bone in humans. Studies available suggest that treatment with thiazolidinediones, primarily rosiglitazone, contributes to bone loss. The effect appears to be most prominent in postmenopausal women. More studies are needed to better understand the effects of thiazolidinediones on bone and fracture rates.

Glycemic Monitoring in Diabetics with Sickle Cell Plus β-Thalassemia Hemoglobinopathy

OBJECTIVE: To report a case of diabetes management in a patient with a hemoglobinopathy that caused her clinician to seek a different measure of glycemic control, fructosamine, rather than glycosylated hemoglobin (HbA1c). CASE SUMMARY: A 53-year-old African American woman presented with a past medical history of type 2 diabetes, hypertension, seizure disorder, rheumatoid arthritis, and sickle cell disease plus β-thalassemia. She reported fasting blood glucose values ranging broadly from 50 to 320 mg/dL, yet her HbA1c result remained steady in a low range of >6%. A measure of fructosamine returned elevated at 340 μmol/L (reference range 200–300%). DISCUSSION: We believe that this patients hemoglobinopathy resulted in falsely low levels of HbA1c, and we substantiate this interpretation with the patients self-monitored blood glucose values from home that appeared higher and inconsistent with the HbA1c results. Although few reports on using the measure of fructosamine appear in the literature, this patients high fructosamine result supports fructosamine as the more appropriate measure of glycemic control. CONCLUSIONS: Serum fructosamine levels may be considered as an appropriate laboratory measurement when monitoring long-term glycemic control in patients with type 2 diabetes mellitus and sickle cell disease.

A Renaissance in Pharmacy Education at the University of North Carolina at Chapel Hill

The UNC Eshelman School of Pharmacy is transforming its doctor of pharmacy program to emphasize active engagement of students in the classroom, foster scientific inquiry and innovation, and immerse students in patient care early in their education. The admissions process is also being reengineered.

New and Emerging Strategies for Reducing Cardiometabolic Risk Factors

Several new drug therapies with beneficial effects on more than one of the cardiometabolic risk factors that contribute to the metabolic syndrome have been developed recently or are under investigation. Emerging risk factors for coronary heart disease (CHD), including low concentrations of high‐density lipoprotein (HDL) cholesterol and apolipoprotein A‐1 (apoA‐1), high levels of high‐sensitivity C‐reactive protein, and small dense low‐density lipoprotein cholesterol particles, have been identified. We provide a detailed description of the mechanisms of action and findings from clinical trials of the new drug therapies and discuss established drug therapies with beneficial effects on emerging risk factors for CHD. The new and emerging drug therapies include an antiobesity agent that reduces atherogenic dyslipidemia and abnormal glucose metabolism; cholesteryl ester transfer protein inhibitors that increase HDL cholesterol and apoA‐1 levels; glitazars that increase HDL cholesterol and decrease triglyceride concentrations, as well as improve abnormal glucose metabolism; and the amylin analog pramlintide and the incretin mimetic exenatide, both of which reduce body weight as well as improve abnormal glucose metabolism. The insulin‐sensitizing effects of angiotensin‐converting enzyme inhibitors and angiotensin II receptor blockers (ARBs), which may help prevent new‐onset diabetes mellitus, and the beneficial effects of the ARB telmisartan on the glucose and lipid profiles also are presented.

Improved Organizational Outcomes Associated With Incorporation of Early Clinical Experiences for Second-Year Student Pharmacists at an Academic Medical Center

Purpose: To assess the feasibility of engaging second professional year student pharmacists in the medication reconciliation process on hospital and health system pharmacy practice outcomes. Methods: Student pharmacists in their second professional year in the Doctor of Pharmacy degree program at our institution were randomly selected from volunteers to participate. Each participant completed training prior to completing three 5-hour evening shifts. Organizational metrics, student pharmacist perception regarding quality of interactions with health care professionals, and pharmacist perceptions were collected. Results: A total of 83 medication histories were performed on complex medical patients (57.0 ± 19.2 years, 51% female, 65% Caucasian, 12 ± 6 medications); of those, 93% were completed within 24 hours of hospital admission. Second professional student pharmacists completed on average 1.9 ± 0.6 medication histories per shift (range 1-3). Student pharmacists identified 0.9 medication-related problems per patient in collaboration with a pharmacist preceptor. Student pharmacists believed the quality of their interactions with health care professionals in the Student Medication and Reconciliation Team (SMART) program was good or excellent. The program has been well received by clinical pharmacists involved in its design and implementation. Conclusion: This study provides evidence that second professional year student pharmacists can assist pharmacy departments in the care of medically complex patients upon hospital admission.

Early Clinical Experiences for Second-Year Student Pharmacists at an Academic Medical Center

Objective. To examine student outcomes associated with the Student Medication and Reconciliation Team (SMART) program, which was designed to provide second-year student pharmacists at the University of North Carolina (UNC) Eshelman School of Pharmacy direct patient care experience at UNC Medical Center. Design. Twenty-two second-year student pharmacists were randomly selected from volunteers, given program training, and scheduled for three 5-hour evening shifts in 2013-2014. Pre/post surveys and reflection statements were collected from 19 students. Data were analyzed with a mixed methods approach. Assessment. Survey results revealed an increase in student self-efficacy (p<0.05) and positive perceptions of SMART. Qualitative findings suggest the program provided opportunities for students to develop strategies for practice, promoted an appreciation for the various roles pharmacists play in health care, and fostered an appreciation for the complexity of real-world practice. Conclusion. Early clinical experiences can enhance student learning and development while fostering an appreciation for pharmacy practice.

Famotidine-associated mental status changes

A 77‐year‐old man who had taken ranitidine for several years for dyspepsia was prescribed alternative therapy with famotidine 20 mg twice/day. He subsequently developed mental status changes, with confusion, disorientation, and nightmares. The symptoms dissipated after he discontinued famotidine for 2 days. He rechallenged himself and experienced return of the symptoms shortly thereafter, with additional visual hallucinations. His therapy was changed to lansoprazole, and his symptoms again disappeared and have not recurred. Case reports of central nervous system effects with other histamine2 antagonists have been published. Eight cases occurred with famotidine, all of which were in hospitalized patients receiving intravenous famotidine. We believe this is the first report of mental status changes in an ambulatory patient taking oral famotidine. The elderly may be particularly susceptible to such changes.

Limited Predictive Utility of Admissions Scores and Objective Structured Clinical Examinations for APPE Performance

Objective. To examine the relationship between admissions, objective structured clinical examination (OSCE), and advanced pharmacy practice experience (APPE) scores. Methods. Admissions, OSCE, and APPE scores were collected for students who graduated from the doctor of pharmacy (PharmD) program in spring of 2012 and spring of 2013 (n=289). Pearson correlation was used to examine relationships between variables, and independent t test was used to compare mean scores between groups. Results. All relationships among admissions data (undergraduate grade point average, composite PCAT scores, and interview scores) and OSCE and APPE scores were weak, with the strongest association found between the final OSCE and ambulatory care APPEs. Students with low scores on the final OSCE performed lower than others on the acute care, ambulatory care, and community APPEs. Conclusion. This study highlights the complexities of assessing student development of noncognitive professional skills over the course of a curriculum.

The Clinical Significance of the Interaction Between Proton Pump Inhibitors and Clopidogrel

Objective: To determine whether the interaction between omeprazole and clopidogrel is a proton pump inhibitor (PPI) class effect or a drug-specific effect. Data Sources: A MEDLINE search for primary literature was completed (through August 2009) using the search terms proton pump inhibitors and clopidogrel. Additional data obtained from references and abstracts presented at clinical meetings were included when appropriate. Study Selection: Nine primary literature articles were identified and reviewed. This included only one prospective, double-blind, placebo-controlled, randomized trial. The remainder were prospective and retrospective cohort studies and a population-based nested case-control study. Data Extraction: Omeprazole, a CYP2C19 inhibitor, has been shown to increase the platelet reactivity index (PRI) when combined with clopidogrel (52.4% vs 39.8%; p < 0.0001), leading to an increased risk of thrombosis. This combination was also shown to cause a 25% increase in the risk of mortality or rehospitalization for acute coronary syndrome (ACS), with a significantly higher risk for each 10% increase in time on this combination therapy (odds ratio [OR] 1.07; CI 1.05 to 1.09). Conversely, combination therapy with pantoprazole or esomeprazole and clopidogrel caused a nonsignificant increase in PRI (p = 0.382) and adenosine diphosphate-induced platelet aggregation (p = 0.69 and 0.88, respectively). Similarly, the combination of pantoprazole and clopidogrel was not associated with an increased risk of myocardial infarction (OR 1.02 [0.70–1.47]) when patients were followed for 90 days following hospital discharge for ACS. One study has shown a class effect when PPIs are combined with clopidogrel, leading to an increased risk of a major adverse cardiovascular event (hazard ratio 1.51; 1.39 to 1.64). Histamine2 (H2)-receptor antagonists have not been associated with a significant interaction with clopidogrel in any study. Conclusions: The use of PPIs with clopidogrel may be warranted, based on comorbid disease states for many patients, but H2-receptor antagonists should be considered when appropriate, due to their lack of interaction with clopidogrel.