The Struggle is Real: Facilitating Pharmacy Student Success on Rotations When Challenges Arise.

Pharmacy preceptors are pivotal to facilitating and maximizing student learning on experiential rotations. However, preceptors may encounter a variety of behaviors or barriers that can hinder student success. Although some guidance exists for preceptors, emerging learner challenges along with new educational outcomes call for an updated practical approach to promoting student success on rotations. This paper provides preceptors with a structured approach to facilitate success for students who exhibit challenges on rotations. Four categories that preceptors can use to identify behaviors and barriers to learning are outlined - knowledge, skills, professional attitudes and behaviors, and external factors including the Social Determinants of Learning™. We describe strategies to help preceptors identify and categorize these challenges and provide a stepwise approach to facilitate student success.

Evaluation of an ambulatory care elective to improve practice readiness perceptions utilizing entry-level competencies.

BACKGROUND AND PURPOSE: The objectives of this study are to (1) describe the impact of an ambulatory care elective on students' future interests in ambulatory care careers and (2) evaluate students' perception of practice readiness using entry-level competencies. EDUCATIONAL ACTIVITY AND SETTING: This study employed a mixed methods approach to provide a comprehensive evaluation of a newly designed ambulatory care elective. A pre-post survey was developed to evaluate students' career plans and perceptions of practice readiness in an ambulatory care setting. The primary outcome analyzed the change in students' career plans and pre-post changes in self-perceptions using the institutional advanced pharmacy practice experience (APPE) ambulatory care rotation assessment and key skills from the American Society of Health-System Pharmacists entry-level readiness objectives. A qualitative analysis was also conducted to analyze open-ended response questions within the post-survey as well as the overall course reflections from the students. FINDINGS: There was no significant difference in career plans; however, students' perception of practice readiness for the ambulatory care setting significantly improved following the elective course. SUMMARY: This elective course improved students' perception of practice readiness for the ambulatory care setting. Future research is required to assess the impact of student performance in APPE and post-graduate pursuits.

Mechanisms and Potential Roles of Glucose-Lowering Agents in COVID-19: A Review.

OBJECTIVE: To explore mechanistic benefits of glucose-lowering agents that extend beyond glycemic control with the potential to mitigate coronavirus disease 2019 (COVID-19) complications. DATA SOURCES: The following PubMed literature search terms were used from July 2020 to January 2, 2021: diabetes, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), glucose-lowering agents, and pharmacology. STUDY SELECTION AND DATA EXTRACTION: English-language studies reporting on the association between diabetes, COVID-19 adverse outcomes, and the potential roles of glucose-lowering agents were reviewed. DATA SYNTHESIS: Selected glucose-lowering agents have benefits beyond glycemic control, with the potential to reduce the risks of severe complications during SARS-CoV-2 infection. Key benefits include anti-inflammatory, anticoagulant, immune modulating, and enzyme/receptor effects. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review summarizes the current knowledge of glucose-lowering agents and their potential roles in COVID-19 outcomes. Considering beneficial mechanisms on COVID-19 outcomes that extend beyond glycemic control as well as safety profiles, current data suggest that dipeptidyl peptidase-IV (DPP-IV) inhibitors and metformin may have the most promise and warrant further investigation. CONCLUSIONS: Certain glucose-lowering agents may offer additional benefits beyond glucose control-namely, by modulating the mechanisms contributing to adverse outcomes related to COVID-19 in patients with diabetes. DPP-IV inhibitors and metformin appear to have the most promise. However, current published literature on diabetes medications and COVID-19 should be interpreted with caution. Most published studies are retrospective and consist of convenience samples, and some lack adequate analytical approaches with confounding biases. Ongoing trials aim to evaluate the effects of glucose-lowering agents in reducing the severity of COVID-19 outcomes.

Ambulatory care practice in the COVID-19 era: Redesigning clinical services and experiential learning.

The coronavirus disease (COVID-19) has created a variety of challenges for health care professionals, including ambulatory care clinical pharmacists. High-quality remote and minimal-contact care has become a necessity. Ambulatory care clinical pharmacists around the nation have adjusted their practice. In many cases, this included implementation of telehealth programs for comprehensive medication management. The redesign of ambulatory care Advanced Pharmacy Practice Experiences (APPE) also required quick adaptation. In this paper, we describe the clinical practice and experiential education challenges encountered by an ambulatory care clinical pharmacist workgroup in a COVID-19 "hotspot," with an emphasis on solutions and guidance. We discuss how to adapt ambulatory care clinical pharmacy practices including methods of minimal-contact care, reimbursement opportunities, tracking outcomes, and restructuring ambulatory care APPE. As ambulatory care clinical pharmacists continue to expand the services they provide in response to COVID-19, we also describe opportunities to promote pharmacists as providers during times of pandemic and into the future.

Cultivating a Vibrant and Thriving Elective Curriculum in Pharmacy Schools.

Elective courses are required in Doctor of Pharmacy (PharmD) curricula in the United States, but they may receive less attention than required courses in the core curriculum. Elective courses can serve as a platform for innovation in, experimentation with, and implementation of high-impact educational practices. However, these benefits may not always be realized or maximized. We advocate for an "elective curriculum" that is strategically designed and intentionally planned and managed. Students, faculty members, and administrators all play important roles in creating this curriculum. To ensure the curriculum is vibrant and thriving, attention is needed to: alignment with institutional missions, meeting the postgraduation needs of students and employers, enhancing faculty development and faculty experience, strengthening partnerships within the university and/or external entities, and moving the profession forward.

Understandability, actionability, and readability of online patient education materials about diabetes mellitus.

PURPOSE: The purpose of this study was to assess the understandability, actionability, and readability of online diabetes education materials. SUMMARY: This was a descriptive study that identified printable diabetes education materials through an online search. Materials were included from the following sources: national organizations with materials approved by expert panels, corporations with materials subject to FDA approval, and not-for-profit organizations with inter-professional advisory boards to approve materials. Topics included were basic knowledge of diabetes, hypoglycemia, insulin, and blood sugar goals. Materials were excluded if they were non-printable, contained active links, had a publication date prior to January 2011, were greater than 2 pages in length, or were pediatric focused. Understandability and actionability of the patient education materials were evaluated using the Patient Education Materials Assessment Tool (PEMAT). Descriptive statistics and inter-rater reliability analysis using the kappa statistic were utilized. Readability was assessed using the Flesch-Kincaid Grade Level and Simple Measure of Gobbledygook (SMOG) formula. Pearson correlation coefficient was calculated to assess the relationship between reading grade level and PEMAT scores. In total, 25 websites were identified, 5 of which met the inclusion criteria; 13 patient education materials were included, PEMAT scoring revealed that 4 of these met the criteria for understandability and only 1 met the criteria for actionability. There was no correlation found between PEMAT scores and reading grade levels (Pearson correlation coefficient = -0.30, p = 0.325). CONCLUSION: The majority of diabetes patient education materials reviewed scored poorly using the PEMAT. Future development of diabetes patient education materials should be designed with the goal of increasing understandability and actionability.

Does Dapagliflozin Affect Energy Intake and Appetite? A Randomized, Controlled Exploratory Study in Healthy Subjects.

The primary aims of this study were to assess the effects of dapagliflozin versus placebo on energy intake and appetite ratings in healthy individuals. This was a randomized, single-blind, placebo-controlled, 2-period crossover study. In each period, healthy individuals received either dapagliflozin or placebo for 2 weeks. On assessment days, participants were asked to consume a standard preload breakfast. Appetite ratings were measured with 100-mm visual analog scales immediately before and during the 4.25-hour period after breakfast. Energy intake was measured at an ad libitum lunch. Energy intake and appetite responses were assessed at the end of each 2-week treatment period by mixed-design analysis of variance. Eighteen individuals completed all assessments (44% female; mean age, 22.8 years; 44% Caucasian; mean BMI, 25.2 kg/m2 ). There was no difference in energy intake on dapagliflozin compared to placebo (mean difference, -19.8 kcal; P = .516). Mean differences in prebreakfast desire for salty foods (11.3 mm, P = .094) and postbreakfast desire for sweet foods (8.1 mm, P = .054) trended higher with dapagliflozin relative to placebo. Our data do not support an effect of dapagliflozin on energy intake or appetite measures in young, healthy subjects. Although not statistically significant, the size of the mean differences in prebreakfast desire for salty foods and postbreakfast desire for sweet foods on dapagliflozin were larger than placebo and reflect the drug's natriuretic and glucuretic effects. These findings should be further evaluated in patients with type 2 diabetes.

Aspirin for primary prevention of cardiovascular disease in patients with diabetes: A meta-analysis.

AIMS: Aspirin use for primary prevention of cardiovascular disease (CVD) is controversial, especially in patients with diabetes. The objective of this meta-analysis was to evaluate aspirin's safety and efficacy for primary prevention of CVD [fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, angina, transient ischemic attack (TIA), peripheral artery disease (PAD) and revascularization] in patients with diabetes. METHODS: A literature search was conducted using the terms cardiovascular disease, aspirin, diabetes mellitus to identify trials of patients with diabetes who received aspirin for primary prevention of CVD. Study sample size, and ischemic and bleeding events were extracted and analyzed using RevMan 5.2.7. RESULTS: In total, 6 studies (n=10,117) met criteria. Aspirin doses ranged from 100mg every other day to 650mg daily. Follow-up ranged from 3.6 to 10.1years. In patients with diabetes, there was no difference between aspirin and placebo with respect to the risk of all cause mortality (OR 0.93, 95% CI 0.81-1.06), or individual atherosclerotic events compared to placebo. There were no differences in bleeding (OR 2.53, 95% CI 0.77-8.34), GI bleeding (OR 2.14, 95% CI 0.63-7.33) or hemorrhagic stroke rates (OR 0.90, 0.34-2.33) between groups. CONCLUSIONS: It remains unclear whether aspirin may reduce the occurrence of a first atherosclerotic event or mortality in patients with diabetes. More research on this use of aspirin in patients with diabetes is required to supplement currently available research.

Enhancing Academic Success by Creating a Community of Learners.

OBJECTIVE: To enhance academic performance and student progression by creating a community of learners. DESIGN: Academic performance and student progression of students participating in the first 3 years of a second-year pharmacy learning community were compared with those of students in the 3 previous classes. Students participating in the learning community completed surveys at the end of each semester and at the end of the academic year. Peer mentors were surveyed at the end of the academic year. ASSESSMENT: After implementing the learning community, failures during the second year of the pharmacy program decreased. Students had increasingly positive perceptions of the experience over the 3 years. Peer mentors rated their overall experience highly. CONCLUSION: Implementation of a learning community resulted in improved progression through the program and was well received by students.

Clinical pharmacists as key members of the patient-centered medical home: an opinion statement of the Ambulatory Care Practice and Research Network of the American College of Clinical Pharmacy.

The American College of Clinical Pharmacy (ACCP) Ambulatory Care Practice Research Network (PRN) considers the role of clinical pharmacists to be fundamental to the success of the Patient-Centered Medical Home (PCMH) model. Within the PCMH, pharmacists can improve the health of populations by participating in activities that optimize medication management. Multiple published articles support clinical pharmacist involvement in the PCMH with regard to promotion of team-based care, enhanced access, care coordination, and improved quality and safety of care. A survey of clinical pharmacist members of ACCP who operate in such a model depict a variety of activities, with some members pioneering new and innovative ways to practice clinical pharmacy. Although this is a significant opportunity for pharmacists in the primary care setting, a unified vision of pharmacy services is needed. It is our hope that with continued efforts focused on obtaining national provider status, clinical pharmacy can use the PCMH model to solidify the future of primary care pharmacy. The following is an opinion statement of the ACCP Ambulatory Care PRN regarding the vital role of clinical pharmacists in the PCMH.

Evaluation of lorcaserin for the treatment of obesity.

INTRODUCTION: Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from baseline with lorcaserin compared to 2.5% with placebo and over twice as many patients achieved ≥ 5% weight loss. Patients with diabetes achieved mean weight loss of 4.5% with lorcaserin compared to 1.5% with placebo as well as modest improvements in glycemic outcomes. AREAS COVERED: The authors review the pharmacology and clinical efficacy as well as the safety and tolerability of lorcaserin. This was achieved through a PubMed search (1960 - present) on lorcaserin to generate the key literature in the area. The lorcaserin package insert and Food and Drug Administration briefing documents were also used to identify relevant information. To assess long-term clinical efficacy and safety, the authors used studies with a minimum duration of one year. EXPERT OPINION: Lorcaserin induces moderate but significant weight loss compared to placebo as an adjunct to lifestyle modification. Although head-to-head comparison trials are not available, lorcaserin is likely less effective but better tolerated than its recently approved competitor, phentermine/topiramate. Cardiovascular outcome data will be invaluable in determining lorcaserin's eventual utilization and place in therapy.

Glucagon-like peptide-1 receptor agonists as add-on therapy to basal insulin in patients with type 2 diabetes: a systematic review.

The prevalence of obesity and diabetes continues to rise in the US. Glucagon-like peptide-1 receptor agonist (GLP-1RA) is an effective treatment option for type 2 diabetes mellitus (T2DM) that promotes weight loss. Common and effective treatment options added to metformin therapy (basal insulin, sulfonylureas, and pioglitazone) contribute to weight gain, which makes the addition of GLP-1RAs advantageous. Exenatide was the first agent in this class and has recently been approved for use in combination with insulin glargine by the US Food and Drug Administration and the European Medicines Agency. Until recently, there was a lack of data examining basal insulin combined with these agents. The main purpose of this article is to review the prospective interventional data on the safety and efficacy of GLP-1RAs (exenatide, liraglutide, albiglutide, lixisenatide) combined with basal insulin therapy in nonpregnant adults with T2DM. Databases searched were PubMed, Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews (inception to January 2012). Abstracts presented at relevant diabetes and endocrine meetings from 2009 to 2011 were also reviewed, as were reference lists of identified publications. A total of five studies met the criteria and were included in the review. Data from these studies demonstrated that this combination therapy offers advantages for the treatment of diabetes, such as additional lowering of A1c without major risk for hypoglycemia, lower basal insulin requirements, decreased postprandial glucose levels (with or without fasting plasma glucose decreases), and weight loss, or at the very least, less weight gain. However, the gastrointestinal side effects and high cost of these agents may limit their use. This review demonstrates that adding a GLP-1RA to an existing basal insulin regimen is a reasonable treatment strategy in nonpregnant adult patients with T2DM.

Lorcaserin: an investigational serotonin 2C agonist for weight loss.

PURPOSE: The pharmacology, pharmacokinetics, and adverse effects of the selective serotonin (5-HT) agonist lorcaserin are reviewed, with an emphasis on efficacy and safety data from Phase III clinical trials. SUMMARY: Lorcaserin is highly selective for a subtype of 5-HT receptors important in appetite regulation, with low affinity for other 5-HT-receptor subtypes whose activation is thought to underlie serious cardiovascular adverse effects; such effects have been seen with nonselective serotonergic agents for weight loss (e.g., fenfluramine). In two Phase III trials of lorcaserin, the cumulative proportion of patients who achieved weight loss of ≥5% over 12 months was about 47% with lorcaserin use versus 20-25% among placebo users (p < 0.0001 for both trials). Lorcaserin was generally well tolerated in the clinical trials to date; nausea and vomiting, headache, and dizziness were the most commonly reported adverse effects. In two of the three Phase III trials to date, lorcaserin use was not found to increase the risk of cardiac valvulopathy; however, in the other Phase III trial, which focused on patients with diabetes, lorcaserin use was associated with an increased rate of new valvulopathy. In a carcinogenicity evaluation involving laboratory rats, lorcaserin was linked to the development of various malignancies, a finding with uncertain implications for its potential future use in humans. CONCLUSION: Lorcaserin, a 5-HT(2C) agonist, has demonstrated efficacy in patients who are obese or are overweight with associated comorbidities. Phase III trials have found that more than 35% of patients lost greater than 5% of their baseline weight. The maker of lorcaserin has indicated it will continue to seek U.S. marketing approval of the drug for the indications of long-term weight loss and weight-loss maintenance in specific patient populations.

Diabetes medications related to an increased risk of falls and fall-related morbidity in the elderly.

OBJECTIVE: To review literature regarding the effect of diabetes medications as a contributing risk for falls and fall-related morbidity in elderly patients with type 2 diabetes. DATA SOURCES: Primary literature was identified through PubMed MEDLINE (1966-November 2009) using the search terms elderly, aged, older adults, diabetes type 2, diabetes mellitus, falls, fractures, medication, hypoglycemia, and vitamin B(12) deficiency. Each drug class and the individual agents within the classes were also included in the search. Additional references were obtained through review of references from articles obtained. STUDY SELECTION AND DATA EXTRACTION: Clinical studies evaluating diabetes medications and their association with falls, as well as studies evaluating their association with the complications of falls, were considered for inclusion. Selection emphasis was placed on randomized studies evaluating diabetes medications and falls. DATA SYNTHESIS: There is no direct link between metformin and falls; however, an indirect association caused by neuropathy secondary to vitamin B(12) deficiency may be of concern. Although hypoglycemia is a risk factor, to date, there are no trials specifically linking insulin secretagogues to falls. Insulin use has been demonstrated to increase the risk of falls in the elderly. Thiazolidinediones increase fracture risk and thus may worsen fall-related outcomes. There are no studies to date linking other agents to an increased risk of falls. CONCLUSIONS: Special considerations should be made when treating elderly patients with diabetes. At this time, a patient's functional level and risk factors for falls should weigh into decision-making regarding drug selection. The risk of falls and fall-related complications associated with diabetes medications should not be ignored.

Risk perception for developing diabetes among pharmacists.

BACKGROUND: Emerging evidence implies that differences in risk perception between healthcare professionals and the lay public exist. OBJECTIVE: To compare the actual risk status versus the personal risk perceptions for developing diabetes among pharmacists. METHODS: Perceived risk was measured in this cross-sectional study with the validated Risk Perception Survey for Developing Diabetes (RPS-DD). The RPS-DD has 4 main subscales aimed at capturing multiple dimensions of perceived risk and is scored on the following scale: 1 (almost no risk), 2 (slight risk), 3 (moderate risk), and 4 (high risk). Actual risk was assigned according to the American Diabetes Association (ADA) Diabetes Risk Test. Differences between higher and lower ADA risk participants were analyzed. Regression analyses were conducted to examine risk factors associated with pharmacists' self-reported perception for developing diabetes. RESULTS: Pharmacists (N = 218, 46.2 +/- 12.2 years [mean +/- SD], 47.7% male, 85.9% white) completed the survey. The Comparative Disease and Environmental Risk mean subscale scores were 1.98 +/- 0.43 and 1.86 +/- 0.41, indicating slight risk perceptions for the subscales, respectively. The single-item self-reported perceived risk for developing diabetes was 2.25 +/- 0.90, indicating a slight to moderate perceived risk for this disease. The Optimistic Bias score was 2.60 +/- 0.64, suggesting a trend toward more optimistic bias and a lower perceived risk for the development of diabetes. The Personal Control score was 3.38 +/- 0.47, illustrating that pharmacists endorsed personal control over the development of diabetes. Higher ADA risk participants reported less optimistic bias compared with lower risk respondents (p = 0.005). Comparative disease risk perception (correlation [r] = 0.38; p < 0.0001) and degree of optimistic bias (r = -0.49; p < 0.0001) emerged as the only predictors for diabetes related risk perception CONCLUSIONS: Pharmacists exhibited a slight to moderate risk perception for developing diabetes, reported a trend toward more optimistic bias, and demonstrated personal control over developing diabetes. Significant comparisons between higher and lower risk respondents were observed only with the optimistic bias subscale.

Quality of diabetes care in Arab Americans.

The quality of care received by Arab American patients with type 2 diabetes residing in a city with a large migrant Arab population has not been examined. Arab American adults with a self-reported diagnosis of diabetes were identified in a rigorous cross-sectional, population-based epidemiologic study conducted in Dearborn, MI. Quality of diabetes care was determined by assessing adherence to the American Diabetes Association (ADA) clinical practice recommendations. The Third National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS) provided data for a national comparison. Among the 53 participants, mean age was 59+/-12 years and the mean duration of diabetes was 11.3+/-13.3 years. The ADA goal for an A1c of <7% was met by 30% of study subjects. LDL (<100mg/dL) and BP (<130/85) goals were met by 36% and 16% of subjects, respectively. The majority of the Arab American subjects studied were treated less aggressively with pharmacologic agents than recommended by the ADA. 26% of the Arab Americans had an A1c>9.5% as compared to 18% of the national population. Arab Americans generally had worse blood pressure control but better lipid control compared to the national sample. This is the first report of the quality of diabetes care in an Arab American population, and demonstrates sub-optimal quality of care according to the ADA clinical practice recommendations.

Health issues in the Arab American community. The use of glucose-lowering agents and aspirin among Arab Americans with diabetes.

OBJECTIVE: Little is known about the health outcomes or the quality of care among Arab American patients with diabetes. The objective of this study is to examine the use of glucose-lowering agents and aspirin therapy in this population compared to the drug utilization patterns reported in nationally representative surveys. RESEARCH DESIGN AND METHODS: A random sample of adult Arab American patients with self-reported diabetes was selected. Complete medication histories were recorded during a face-to-face interview. Medication utilization of the glucose-lowering agents and aspirin were compared to data from the Third National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS). RESULTS: The study sample consisted of 53 participants (20 males, 33 females) with mean age +/- SD of 59.4 +/- 12 years and A1C levels of 8.0 +/- 2%. Compared to US adults, Arab American patients with diabetes were less likely to be treated with insulin (27% vs 17%) and more likely to receive oral hypoglycemic agents (65% vs 81%). Similar proportions of participants were maintained on insulin-oral hypoglycemic-combined therapy (10% US adults vs 9% Arab Americans). Aspirin use was significantly lower among the study participants (23%) compared to the reported national prevalence of aspirin intake (64%). CONCLUSION: The therapeutic management of diabetes in the Arab-American patients with diabetes is suboptimal. The use of insulin and aspirin was lower than that reported by participants in the NHANES and BRFSS national databases. More aggressive approaches for the management of hyperglycemia and the prevention of cardiovascular diseases are needed to improve health outcomes in the Arab-American community.

Evolution of peroxisome proliferator-activated receptor agonists.

OBJECTIVE: To discuss the evolution of peroxisome proliferator-activated receptor (PPAR) agonists from single site to multiple subtype or partial agonists for the treatment of type 2 diabetes, dyslipidemia, obesity, and the metabolic syndrome. DATA SOURCES: Information was obtained from MEDLINE (1966-March 2007) using search terms peroxisome proliferator-activated receptor agonist, PPAR dual agonist, PPAR alpha/gamma agonist, PPAR pan agonist, partial PPAR, and the specific compound names. Other sources included pharmaceutical companies, the Internet, and the American Diabetes Association 64th-66th Scientific Sessions abstract books. STUDY SELECTION AND DATA EXTRACTION: Animal data, abstracts, clinical trials, and review articles were reviewed and summarized. DATA SYNTHESIS: PPAR alpha, gamma, and delta receptors play an important role in lipid metabolism, regulation of adipocyte proliferation and differentiation, and insulin sensitivity. The PPAR dual agonists were developed to combine the triglyceride lowering and high-density lipoprotein cholesterol elevation from the PPAR-alpha agonists (fibrates) with the insulin sensitivity improvement from the PPAR-gamma agonists (thiazolidinediones). Although the dual agonists reduced hemoglobin A(1C) (A1C) and improved the lipid profile, adverse effects led to discontinued development. Currently, PPAR-delta agonists (GW501516 in Phase I trials), partial PPAR-gamma agonists (metaglidasen in Phase II and III trials), and pan agonists (alpha, gamma, delta; netoglitazone in Phase II and III trials) with improved cell and tissue selectivity are undergoing investigation to address multiple aspects of the metabolic syndrome with a single medication. By decreasing both A1C and triglycerides, metaglidasen did improve multiple aspects of the metabolic syndrome with fewer adverse effects than compared with placebo. Metaglidasen is now being compared with pioglitazone. CONCLUSIONS: Influencing the various PPARs results in improved glucose, lipid, and weight management, with effects dependent on full or partial agonist activity at single or multiple receptors. Although the dual PPAR compounds have been associated with unacceptable toxicities, new PPAR agonist medications continue to be developed and investigated to discover a safe drug with benefits in multiple disease states.

Thiazolidinediones and the risk of edema: a meta-analysis.

The use of thiazolidinediones (TZDs) in the management of type 2 diabetes mellitus (T2DM) has been associated with an increased risk of peripheral edema. A meta-analysis was performed to assess the overall risk for developing edema secondary to TZD. A systematic literature search was conducted using five electronic databases. All prospective, randomized, either placebo-controlled or comparative studies reporting the incidence of edema with TZD therapy were included. Odds ratios were generated by pooling estimates across the studies. The analysis included 26 studies consisting of 15,332 patients with T2DM. The pooled odds ratio for TZD induced edema was 2.26 (95% CI: 2.02-2.53). The results yielded a higher risk for developing edema with rosiglitazone (3.75 [2.70-5.20]) compared to pioglitazone (2.42 [1.90-3.08]). Concordant results persisted with calculations of the adjusted indirect estimate. This meta-analysis demonstrates at least a two-fold increase in the risk for developing edema with a TZD agent. The risk appears to be greater with rosiglitazone than with pioglitazone. Further studies are needed to explore this difference.