Joshua W. Fleming

New Obesity Agents: Lorcaserin and Phentermine/Topiramate

OBJECTIVE To evaluate the evidence for lorcaserin and phentermine/topiramate in the treatment of obesity. DATA SOURCES Literature was accessed through PubMed (June 1975-March 2013) using the search terms lorcaserin, phentermine, topiramate, or phentermine/topiramate. Additionally, reference citations from publications identified were reviewed. Additional information was obtained from the Food and Drug Administration (FDA)–approved prescribing information and FDA briefing documents. STUDY SELECTION AND DATA EXTRACTION English-language articles focusing on Phase 3 clinical trials for obesity were critiqued. Data from preclinical and Phase 1 and/or 2 trials are reported when appropriate. Six prospective Phase 3 trials were reviewed. DATA SYNTHESIS Obesity has reached epidemic proportions, affecting more than one third of adults in the US. Two medication products, lorcaserin and phentermine/topiramate, have recently received FDA approval as adjuncts to a reduced-calorie diet and increased physical activity among individuals with a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 27 kg/m2 with an obesity-related comorbidity, such as hypertension, dyslipidemia, or diabetes. Lorcaserin is a selective serotonin 5-HT2C agonist that regulates food intake, while the combination of phentermine/topiramate causes appetite suppression and enhanced satiety. Three Phase 3 randomized, placebo-controlled trials reported approximately 75% and 45% of patients achieved greater than or equal to 5% weight loss with phentermine/topiramate and lorcaserin, respectively. CONCLUSIONS With lifestyle modification, phentermine/topiramate appears most effective in terms of weight loss. Lorcaserin demonstrates moderate efficacy. Long-term cardiovascular outcomes studies are needed to confirm the safety and benefit of these new obesity agents.

Resistant Nonalcoholic Fatty Liver Disease Amelioration With Rosuvastatin and Pioglitazone Combination Therapy in a Patient With Metabolic Syndrome

Objective: To report a case describing resolution of persistently elevated aminotransferases in a patient with severe, resistant nonalcoholic fatty liver disease (NAFLD) using combination therapy. Case Summary: A 47-year-old obese male patient presented with a history of elevated aminotransferases and numerous statin intolerances. In addition to worsening control of diabetes and dyslipidemia, severe NAFLD was confirmed. Rosuvastatin was started, which induced short-term elevations in aminotransferases resulting in patient discontinuation. Biochemical markers of NAFLD worsened over time. Therefore, both rosuvastatin 20 mg daily and pioglitazone 15 mg daily were started simultaneously to potentially blunt the early increase in transaminases seen with rosuvastatin. At 2 weeks, the patient’s alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had decreased 57% and 56% from baseline, respectively. By 9 months, the patient’s ALT and AST serum concentrations had normalized. Repeat liver ultrasound demonstrated improvement in steatosis grading and reduction in liver size. These improvements occurred despite a 4.5-kg weight gain since starting rosuvastatin and pioglitazone. Discussion: Pharmacotherapy in NAFLD is not well validated, particularly combination therapy. Medications that target obesity-related consequences are commonly used, although evidence regarding biochemical and histological improvement is inconclusive. Consideration should be given to the use of combination of thiazolidinediones and statins for rapid biochemical improvement and long-term histological impact. Conclusions: The improvement in this patient’s biochemical and ultrasonographic markers of resistant, severe NAFLD was rapid and sustained with combination therapy. This case represents a potential solution for initiating or maintaining statin therapy in patients with NAFLD who are at high cardiovascular risk.

Afrezza: An inhaled approach to insulin delivery

Purpose The purpose of this article is to educate nurse practitioners about Afrezza. Data sources A comprehensive literature search was conducted using MEDLINE for clinical trial data. Information from the Centers of Disease Control and Prevention, World Health Organization, clinical guidelines, Food and Drug Administration labeling, briefings, and press releases was also utilized. Conclusions Afrezza represents a promising noninjectable insulin delivery option for type 1 and type 2 diabetes mellitus. According to clinical trial evidence, it appears to be efficacious and comparable to currently available prandial insulin options, and based on current data, it appears to be a safe alternative to injectable insulin with high treatment satisfaction. Implications for practice Afrezza may offer an alternative for insulin naive patients who are hesitant about initiating traditional insulin. It may cause less weight gain when compared to subcutaneous mealtime insulin with a more rapid absorption and elimination profile, but more long-term studies are needed. Afrezza is limited in type 1 diabetes to use in combination with basal insulin. It is not recommended in the treatment of diabetic ketoacidosis or for patients who smoke. It is contraindicated during hypoglycemic episodes, in chronic lung diseases, or in those with hypersensitivity to regular human insulin or any of the excipients in Afrezza.Purpose:The purpose of this article is to educate nurse practitioners about Afrezza. Data sources:A comprehensive literature search was conducted using MEDLINE for clinical trial data. Information from the Centers of Disease Control and Prevention, World Health Organization, clinical guidelines, Food and Drug Administration labeling, briefings, and press releases was also utilized. Conclusions:Afrezza represents a promising noninjectable insulin delivery option for type 1 and type 2 diabetes mellitus. According to clinical trial evidence, it appears to be efficacious and comparable to currently available prandial insulin options, and based on current data, it appears to be a safe alternative to injectable insulin with high treatment satisfaction. Implications for practice:Afrezza may offer an alternative for insulin naïve patients who are hesitant about initiating traditional insulin. It may cause less weight gain when compared to subcutaneous mealtime insulin with a more rapid absorption and elimination profile, but more long‐term studies are needed. Afrezza is limited in type 1 diabetes to use in combination with basal insulin. It is not recommended in the treatment of diabetic ketoacidosis or for patients who smoke. It is contraindicated during hypoglycemic episodes, in chronic lung diseases, or in those with hypersensitivity to regular human insulin or any of the excipients in Afrezza.

Sodium glucose co-transporter 2 inhibitors: a novel approach to the management of type 2 diabetes mellitus.

Purpose The purpose of this article is to educate nurse practitioners about the newest class of oral medications developed to treat type 2 diabetes mellitus (T2DM). This article will review dapagliflozin and canagliflozin, the two Food and Drug Administration (FDA) approved sodium glucose co-transporter 2 (SGLT2) inhibitors, and discuss their place in therapy. Data sources A comprehensive literature search was conducted using MEDLINE with the key terms: dapagliflozin, canagliflozin, SGLT2 inhibitors, and SGLT2 inhibitors. Other resources included the World Health Organization (WHO), U.S. FDA, Centers for Disease Control and Prevention (CDC), clinical guidelines, FDA labeling, briefings, and press releases. Conclusions Dapagliflozin and canagliflozin appear to be safe and moderately effective. SGLT2 inhibitors provide an alternative for dual and triple therapy for T2DM or can be used as monotherapy in patients who cannot tolerate other first-line options. Implications for practice SGLT2 inhibitors have a unique, insulin-independent mechanism of action, targeting the kidneys. They have a low incidence of hypoglycemia and result in a moderate reduction in HbA1C. Improvements in weight, blood pressure, and lipid parameters have been demonstrated. Dosing considerations are required for the elderly, renally impaired, and patients at risk for hypotension.Purpose: The purpose of this article is to educate nurse practitioners about the newest class of oral medications developed to treat type 2 diabetes mellitus (T2DM). This article will review dapagliflozin and canagliflozin, the two Food and Drug Administration (FDA) approved sodium glucose co‐transporter 2 (SGLT2) inhibitors, and discuss their place in therapy. Data sources: A comprehensive literature search was conducted using MEDLINE with the key terms: dapagliflozin, canagliflozin, SGLT2 inhibitors, and SGLT2 inhibitors. Other resources included the World Health Organization (WHO), U.S. FDA, Centers for Disease Control and Prevention (CDC), clinical guidelines, FDA labeling, briefings, and press releases. Conclusions: Dapagliflozin and canagliflozin appear to be safe and moderately effective. SGLT2 inhibitors provide an alternative for dual and triple therapy for T2DM or can be used as monotherapy in patients who cannot tolerate other first‐line options. Implications for practice: SGLT2 inhibitors have a unique, insulin‐independent mechanism of action, targeting the kidneys. They have a low incidence of hypoglycemia and result in a moderate reduction in HbA1C. Improvements in weight, blood pressure, and lipid parameters have been demonstrated. Dosing considerations are required for the elderly, renally impaired, and patients at risk for hypotension.

Fixed-dose combinations in type 2 diabetes - role of the canagliflozin metformin combination.

Canagliflozin–metformin is one of the newest combination therapies available for the treatment of type 2 diabetes mellitus (T2DM). Canagliflozin is an inhibitor of the sodium–glucose co-transporter 2 which causes an increase in the urinary excretion of glucose. In the present article, we review the safety and efficacy of canagliflozin and metformin from data obtained from Phase III metformin add-on therapy clinical trials as there are no studies to date that specifically evaluate the combination of metformin and canagliflozin. Trials included in this review were dual-therapy trials of subjects who were already taking background metformin and were assigned to receive canagliflozin, glimepiride, or sitagliptin. The addition of canagliflozin to metformin resulted in a decrease in HbA1c of 0.73%–0.93%. Canagliflozin 100 mg was considered to be non-inferior to glimepiride and sitagliptin 100 mg with the canagliflozin 300 mg dose being statistically superior to sitagliptin and glimepiride. Other advantages of the use of canagliflozin are reduction in weight (3.3–4.0 kg) and systolic blood pressure (3.3–4.7 mmHg). The primary disadvantages are potential genital mycotic infections, hypotension, and gastrointestinal side effects from metformin. All things considered, this combination appears to be safe and effective in clinical trials and represents a promising option for the treatment of T2DM.

The role of Toujeo®, insulin glargine U‐300, in the treatment of diabetes mellitus

Purpose The purpose of this article is to educate nurse practitioners about the role of Toujeo®, insulin glargine U-300 (Gla-300), which is a new option for the treatment of diabetes mellitus. Data sources A comprehensive literature search was conducted using MEDLINE with the key terms: insulin glargine 300, Toujeo, Gla-300, and EDITION for clinical trial data. Other resources included package inserts, drug information websites, and the World Health Organization (WHO). Conclusions Gla-300 appears to be a safe and effective option for basal insulin therapy. In clinical trials, it was shown to be equally efficacious as Gla-100 with fewer episodes of hypoglycemia and slightly less weight gain, and subjects receiving Gla-300 required approximately 10 units more basal insulin to obtain the same hemoglobin A1c (HbA1c) as subjects receiving Gla-100. Implications for practice This new basal therapy option represents a potential advantage for patients who require higher doses of insulin because of the higher concentration of Gla-300. The lower incidence of hypoglycemia and more predictable pharmacokinetics could offer a significant therapeutic benefit in difficult-to-control patients with diabetes mellitus. The biggest disadvantage of this product is the slightly higher insulin dosage that is required to improve and/or maintain patients’ HbA1c.

Assessment of clinical productivity tracking via reporting of quality patient indicators

As the role of pharmacists in providing direct patient care continues to expand, the need for and interest in a method for assessing and measuring clinical productivity is becoming more paramount. Unfortunately, there is no consensus on how, when, and which quality indicators or clinical productivity measures should be collected. The primary objective of this study was to assess the landscape of clinical productivity tracking across practice sites.

The impact of participation in a Research/Writing Group on scholarly pursuits by non-tenure track clinical faculty

BACKGROUND AND PURPOSE The purpose of this study was to evaluate the success of a faculty Research/Writing Group (RWG) by quantifying the amount of scholarly productivity from participants in the group compared with that of a matched cohort. EDUCATIONAL ACTIVITY AND SETTING The RWG meets monthly to discuss current projects, providing an assessment of their scholarly activity. Participants offer ideas on improvement, resources and possible platforms for presentations and/or publications. FINDINGS To evaluate the success of this model, scholarly production from the participants in the RWG was compared to a matched group of clinical non-tenure track faculty not participating in the group over a three year period. Faculty perception of RWG participation was evaluated by data collected through a survey using Qualtrics. SUMMARY Participation in the RWG provided these junior faculty the support system to feel confident in their pursuit of scholarly activities; and therefore, they outpaced their counterparts in dissemination of their research.