Karen Whalen

The Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Treatment of Type 2 Diabetes

PURPOSE Diabetes is a chronic metabolic disorder characterized by hyperglycemia that results from insulin resistance, diminished or absent insulin secretion, or both. Approximately one-half of patients with diabetes fail to achieve acceptable glycemic control. Consequently, morbidity and mortality associated with diabetes is high, resulting from complications such as cardiovascular disease and nephropathy. The sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of medications for the treatment of type 2 diabetes. This article provides an overview of efficacy and safety data for the SGLT2 inhibitors and outlines their role in the management of diabetes. METHODS Relevant articles were identified through searches of PubMed and International Pharmaceutical Abstracts by using the key terms canagliflozin, dapagliflozin, empagliflozin, and sodium-glucose co-transporter 2 inhibitor. A review of bibliographies of retrieved articles was also performed to identify additional references. All identified trials published in English and that involved the efficacy and safety of SGLT2 inhibitors in the treatment of type 2 diabetes were reviewed. FINDINGS The SGLT2 inhibitors improve glucose control by increasing urinary glucose excretion. Effectiveness is decreased in the presence of renal dysfunction. These agents are efficacious as monotherapy and add-on therapy for patients with type 2 diabetes uncontrolled on metformin, sulfonylureas, insulin, and other antihyperglycemic combinations. The SGLT2 inhibitors lower glycosylated hemoglobin by 0.5% to 1% and fasting plasma glucose by ~15 to 35 mg/dL, depending on the agent and the dosage used, and are also associated with modest reductions in weight (-1.5 to -3.5 kg) and systolic blood pressure (-3 to -5 mm Hg). Genital mycotic infections and increased urination, owing to the mechanism of action, are the most common adverse effects. In general, the class is well tolerated, and the risk of hypoglycemia is low. IMPLICATIONS With their unique mechanism of action and good safety and tolerability profiles, the SGLT2 inhibitors are an important addition to existing treatments for type 2 diabetes. Because of the lack of data with this class of drugs when current treatment guidelines for diabetes were published, the SGLT2 inhibitors are recommended as second- or third-line therapies for diabetes. Forthcoming data on the long-term efficacy and safety profile of these agents should help to solidify the role of SGLT2 inhibitors in the management of diabetes.

Estradiol Valerate/Dienogest: A Novel Oral Contraceptive

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the new oral contraceptive estradiol valerate/dienogest. Data Sources: Searches of PubMed (1966-July 2011) and International Pharmaceutical Abstracts (1970-July 2011) were conducted using the key words estradiol valerate, dienogest, Natazia, and Olaira. Bibliographies of retrieved articles were reviewed to identify additional références. Study Selection and Data Extraction: All identified studies published in English and involving efficacy and safety of estradiol valerate/dienogest as an oral contraceptive were reviewed. Data Synthesis: Estradiol valerate/dienogest is a 4-phasic oral contraceptive approved for the prevention of pregnancy. The 4-phasic design allows for acceptable cycle control with this hormonal combination. In efficacy trials of estradiol valerate/dienogest in women aged 18–35 years, the Pearl Index ranged from 0.40 to 1.64, a range comparable to that of other combination oral contraceptives. The safety profile was also similar to that of other oral contraceptives, with headache, metrorrhagia, breast tenderness, nausea or vomiting, acne, and weight gain reported as the most common adverse effects. Menstrual bleeding patterns and cycle control with estradiol valerate/dienogest were comparable to those of a monophasic oral contraceptive containing ethinyl estradiol/levonorgestrel. Estradiol valerate/dienogest differs from other oral contraceptives in that il necessitates more stringent dosing guidelines for maximum contraceptive efficacy. New starts should be on the first day of menses only, and a back-up method of contraception is required for the first 9 days, as compared to 7 days with other oral contraceptives. Back-up contraception is usually required for any pill taken more than 12 hours later than scheduled. Conclusions: Estradiol valerate/dienogest is an effective oral contraceptive. Because it has more stringent start times and requires a longer duration of back-up contraception and stricter adherence, estradiol valerate/dienogest should be reserved for patients who are intolerant of other combination oral contraceptives.

Saxagliptin: A New Dipeptidyl Peptidase 4 Inhibitor for Type 2 Diabetes

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of saxagliptin, a new dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes. Data Sources: Searches of PubMed (1966–March 2010) and International Pharmacy Abstracts (1970–March 2010) were conducted using the key words saxagliptin, Onglyza, and BMS-477118. A review of bibliographies of retrieved articles was also performed to identify additional references. Study Selection Ano Data Extraction: All identified studies published in English and involving efficacy and safety of saxagliptin in the treatment of type 2 diabetes were reviewed. Data Synthesis: Saxagliptin is a competitive inhibitor of DPP-4 that stows the degradation of incretin hormones, thereby stimulating insulin secretion, reducing postprandial glucagon, and decreasing glucose levels. Saxagliptin is well absorbed after oral administration and demonstrates a pharmacokinetic profile that is compatible with once-daily dosing. Clinical trials with saxagliptin monotherapy for the treatment of type 2 diabetes showed a reduction in hemoglobin A1c (A1C) of 0.43–0.9%. Saxagliptin has demonstrated similar reductions in A1C when used as add-on therapy with metformin, sulfonylureas, and thiazolidinediones. The combination of saxagliptin and metformin for initial therapy in treatment-naïve patients was associated with greater improvements in A1C than either agent alone. In general, saxagliptin therapy is well tolerated. The most common adverse effects occurring in clinical trials were headache, nasopharyngitis, upper respiratory tract infections, and urinary tract infections. Conclusions: Saxagliptin is effective as monotherapy or add-on therapy for the management of type 2 diabetes. Because saxagliptin has a higher cost and reduces Al C and other surrogate markers of glucose control to a lesser extent than other well-validated therapies, such as metformin, saxagliptin should be reserved for patients who fail or are intolerant of conventional treatments for type 2 diabetes.

Preparation of Faculty Members and Students to Be Citizen Leaders and Pharmacy Advocates

To identify characteristics and quality indicators of best practices for leadership and advocacy development in pharmacy education, a national task force on leadership development in pharmacy invited colleges and schools to complete a phone survey to characterize the courses, processes, and noteworthy practices for leadership and advocacy development at their institution. The literature was consulted to corroborate survey findings and identify additional best practices. Recommendations were derived from the survey results and literature review, as well as from the experience and expertise of task force members. Fifty-four institutions provided information about lecture-based and experiential curricular and noncurricular components of leadership and advocacy development. Successful programs have a supportive institutional culture, faculty and alumni role models, administrative and/or financial support, and a cocurricular thread of activities. Leadership and advocacy development for student pharmacists is increasingly important. The recommendations and suggestions provided can facilitate leadership and advocacy development at other colleges and schools of pharmacy.

Perceptions of Tenure and Tenure Reform in Academic Pharmacy

Objectives. To determine the academic pharmacy community’s perceptions of and recommendations for tenure and tenure reform. Methods. A survey instrument was administered via either a live interview or an online survey instrument to selected members of the US academic pharmacy community. Results. The majority of respondents felt that tenure in academic pharmacy was doing what it was intended to do, which is to provide academic freedom and allow for innovation (59.6%). Respondents raised concern over the need for faculty mentoring before and after achieving tenure, whether tenure adequately recognized service, and that tenure was not the best standard for recognition and achievement. The majority (63%) agreed that tenure reform was needed in academic pharmacy, with the most prevalent recommendation being to implement post-tenure reviews. Some disparities in opinions of tenure reform were seen in the subgroup analyses of clinical science vs basic science faculty members, public vs private institutions, and administrators vs nonadministrators. Conclusions. The majority of respondents want to see tenure reformed in academic pharmacy.

The Impact of a Computerized Potassium Alert on Adverse Drug Events and Pharmacists' Interventions

Background: Hyperkalemia is one of the most common drug-related electrolyte abnormalities resulting in adverse drug events (ADEs) at our institution. Objective: To determine the effect of a computerized pharmacy alert on the number of adverse events related to hyperkalemia in a hospital setting and to study the impact of guidelines and education on pharmacist response to high potassium levels. Methods: An alert was built into the pharmacy computer system, which warned pharmacists about a potassium level greater than 5.1 mEq/L when processing an order that could increase potassium. The alert was linked to a trigger medication list. After the alert was implemented, the number of ADEs due to hyperkalemia was compared for the 3 months pre- and postalert. Due to a lack of consistency in pharmacist interventions after implementation of the alert, hyperkalemia management guidelines were developed by the pharmacy department. The staff pharmacists received training on how to address hyperkalemia when processing prescriptions. After the education component was completed, the types of pharmacist interventions made pre- and posttraining were also compared. Results: Building an automated pop-up alert resulted in a decreased number of ADEs related to hyperkalemia (p < 0.001) and reduced the utilization of medications needed to treat hyperkalemia (p = 0.019). Conclusions: Implementation of a computerized pharmacy alert resulted in a statistically significant decrease in adverse drug events related to hyperkalemia in our institution. Educating pharmacists about hyperkalemia and developing guidelines for its management provided consistency among responses to the high potassium computerized alert. Further studies are needed to evaluate the impact of guideline development and pharmacist education on the trend of drug-induced hyperkalemia in an inpatient pharmacy setting.