Dhiren Patel

Pharmacotherapy for the management of obesity

In the last 30 years, obesity has rapidly increased and obesity-related comorbidities have surged. Once considered to be a problem only in developed nations, obesity has become a global epidemic. Consequently, the costs associated with managing overweight and obesity worldwide are astronomical. The objective of this mini-review is to provide an overview of current options available for obesity management, with a focus on anti-obesity pharmacotherapies. The impact of weight loss on improving obesity-related comorbidities and risk factors has been well documented. Although established clinical guidelines suggest comprehensive lifestyle modification to induce weight loss, many patients do not respond to lifestyle interventions and may not qualify for bariatric surgery. For these patients, pharmacotherapy may serve as a therapeutic option. Several anti-obesity pharmacotherapies, such as phentermine, are indicated for short-term use and are not required to demonstrate clinically meaningful weight loss (i.e., ≥5%). For long-term weight management, the FDA has approved 5 agents so far-orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide. These drugs have shown efficacy in enabling patients to achieve clinically meaningful weight loss and improving cardiometabolic parameters. Healthcare practitioners can help alleviate the obesity epidemic by tailoring these pharmacotherapies based on individual needs, comorbidities, and associated drug safety concerns.

Insulin Degludec: A Novel Basal Insulin Analogue

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data, adverse effects, and potential role in therapy of insulin degludec. DATA SOURCES: Articles were identified using the MEDLINE database (January 1996-December 2012). Abstracts and posters were identified from respective congressional websites and published supplements of the American Diabetes Association, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists (January 2008-December 2012). Clinicaltrials.gov was used to identify any ongoing clinical trials or completed trials whose results had not been presented or published. STUDY SELECTION AND DATA EXTRACTION: All available studies were reviewed for inclusion; pharmacokinetic studies were limited to those reporting human data. DATA SYNTHESIS: Insulin degludec is a novel, ultra-long-acting basal insulin analogue that has a similar safety and efficacy profile when compared with insulin glargine in patients with type 1 or type 2 diabetes. Clinical trials have indicated that there is less hypoglycemia, particularly nocturnal hypoglycemia, associated with this agent. CONCLUSIONS: If insulin degludec is approved, it may offer an alternative basal insulin for patients needing more flexible dosing, having a history of nocturnal hypoglycemia, or those with severe insulin resistance needing a higher concentration of basal insulin.

Obesity as a risk factor for Alzheimer's disease: weighing the evidence

Alzheimers disease (AD) is the sixth leading cause of death in the USA today; therefore, it is imperative that public health initiatives and clinical strategies are developed to prevent and effectively treat AD. Despite the enormous impact that AD has on individuals, families, society, and the health care system, there are no biomarkers to clearly identify those at risk for AD, public health prevention strategies in place, or treatments to address the underlying pathology or stop the progression of AD. There is ample scientific as well as empirical evidence that obesity and its metabolic and vascular comorbidities are related to AD and likely in the causative pathway. Obesity prevention and treatment could prove to be an efficacious and safe approach to preventing AD, a serious and daunting epidemic disease. In this review, we present the current pathophysiological and clinical evidence linking obesity and obesity‐related comorbidities (eg, insulin resistance, hyperglycaemia, and type 2 diabetes) with AD. Additionally, we discuss which population to target and when to consider treatment for AD. Finally, we summarize the current evidence regarding the efficacy of anti‐obesity and anti‐diabetic pharmacotherapeutic agents for the treatment of AD.

Antidiabetic agents and cardiovascular outcomes in patients with heart diseases

Abstract Introduction: This article reviews evidence of the benefits and risk of antidiabetic agents in cardiovascular (CV) outcomes, with a focus on medications approved by the FDA since 2008. Study selection: Peer-reviewed articles were identified from MEDLINE and Current Content databases (both 1966 to 1 October 2016) using the search terms insulin, metformin, rosiglitazone, pioglitazone, glyburide, glipizide, glimepiride, acarbose, miglitol, albiglutide, exenatide, liraglutide, lixisenatide, dulaglutide, pramlintide, meglitinide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, colesevalam, bromocriptine, mortality, myocardial infarction (MI), heart failure (HF), and stroke. Trials were included if they were randomized clinical trials evaluating adult patients (≥18 years) with type 2 diabetes; had a period of intervention and follow-up of ≥12 months; and assessed CV outcomes (CV death, fatal/non-fatal MI or HF) as endpoints. Twenty-three randomized trials were included. Antidiabetic agents: Of agents approved prior to 2008, metformin has not been associated with measurable harm in patients with diabetes in terms of mortality and CV events (and has a trend of benefit). Controversial results existed with the use of sulfonylureas and thiazolidinediones (TZDs) for CV outcomes. Among agents approved after 2008, liraglutide and empagliflozin have been shown to be superior to placebo in improving CV outcomes. Conclusions: The FDA regulatory mandate to demonstrate CV safety in order to approve new diabetes drugs led to an increase in the number of CV outcome trials. However, these trials have placebo-controlled, non-inferiority designs aiming to show absence of CV toxicity. More studies are needed to address other questions, including comparative effectiveness, and longer-term risk versus benefits.

Students’ Attitudes, Academic Performance and Preferences for Content Delivery in a Very Large Self-Care Course Redesign

Objective. To evaluate students’ performance/attitudes toward a flipped team-based learning (TBL) format in a “very large” self-care course based on student content delivery preference. Design. Third-year students enrolled in the course were surveyed regarding elements of redesign and homework completion. Additionally, their performance and incoming grade point average were evaluated. Assessment. A survey was completed by 286 of 305 students. Nineteen percent of respondents preferred traditional content delivery, whereas 30% preferred flipped TBL, 48% preferred a mixed format, and 3% had no preference. The grades achieved in the course were: A (49%), B (48%), C (3%) and D (0%). The majority completed “all” or “most” of the homework, appreciated attributes of course redesign, felt home preparation and in-class activities engaged them, and reported improved communication/evaluation skills. Content delivery preference significantly affected attitudes. Conclusion. Students positively received a flipped team-based learning classroom format, especially those who preferred flipped TBL or mixed content delivery. A minority with preference for traditional teaching style did not enjoy the new format; however, their academic performance did not differ significantly from those who did.

Comparison of long-term knowledge retention in lecture-based versus flipped team-based learning course delivery

OBJECTIVES To determine whether team based learning (TBL) is superior to traditional lecture -based learning in confidence and knowledge retention one year later. DESIGN A survey was administered 17 months after a completion of a required over-the-counter /self-care (OTC) course to two different cohorts of students. The survey assessed confidence and knowledge related to OTC topics. The lecture group had a traditional lecture based classroom experience; the intervention group experienced a TBL format throughout the entire course. ASSESSMENT One hundred forty-seven students of 283 enrolled (51.9%) in the lecture group and 222 of 305 (72.8%) students in the TBL group participated in the knowledge assessment and survey. Demographic data including student grade point averages (GPA) and confidence were similar in both groups. Mean assessment scores (±SD) on OTC knowledge was significantly higher in the traditional lecture based group versus the TBL group; 62.9±19.3 vs. 54.9±15.7 (p=0.001). CONCLUSION Although TBL is thought to improve student engagement and mastery of material, after an initial implementation of TBL, knowledge retention in the long term appears to be lower than lecture based learning.

Deoxycholic Acid (ATX-101) for Reduction of Submental Fat

Objective: To review trials evaluating purified synthetic deoxycholic acid (DCA; ATX-101) for the reduction of submental fat (SMF). Data Sources: A literature search was conducted using MEDLINE (1946 to week 4 of April 2016) and Evidence Based Medicine Database (1974 to 6 May, 2016). Keywords searched included deoxycholic acid, ATX-101, and submental fat. Study Selection and Data Extraction: All human studies published in English that addressed the effects of DCA for the reduction of SMF were selected for analysis. Data Synthesis: Five phase III, multicenter, randomized, double-blinded clinical trials enrolling more than 1700 patients have demonstrated the efficacy of ATX-101 in the reduction of SMF via a variety of validated scales as well as objective measurements. Purified synthetic DCA 2 mg/cm2 injected monthly for 4 to 6 treatment sessions demonstrated improvement in scales evaluated by both clinicians and patients. Improvement in skin caliper measurements of SMF and Magnetic Resonance Imaging (MRI) provide objective evidence of the efficacy of ATX-101. Adverse events (AEs) are very common but are transient and localized to the treatment area. Pain at the injection site is the most common AE, occurring in more than 80% of patients treated. Other common AEs include swelling, bruising, numbness, and induration. Appropriate injection technique is patient specific and requires detailed knowledge of the submental anatomy to minimize AEs. Conclusions: ATX-101 is the first pharmacological intervention approved for the reduction of SMF and offers an alternative to invasive measures to improve the submental profile and positively affect patient self-image.

Angiotensin II type 1 receptor blocker-induced immune thrombocytopenia: a case report

IntroductionThe development of thrombocytopenia after a dose increase in losartan and subsequently after switching the patient to valsartan is reported.Case presentationA 61-year-old Caucasian man presented with epistaxis and gingival bleeding of three weeks duration. Laboratory evaluation revealed a hemoglobin level of 144g/L, a leukocyte count of 16.2×109 cells/L (72.51% neutrophils, 20.1% lymphocytes, 6.8% monocytes, 0.4% eosinophils, 0.2% bands), and a platelet count of 15.0×109 cells/L. Flow cytometry of his peripheral blood showed normal CD4:CD8 ratio and no evidence of any lymphoproliferative disorder. A peripheral smear showed decreased platelets with a few areas of clumping. Four weeks before presentation to the emergency room, his losartan dose was increased to 100mg once daily due to continuously elevated blood pressure readings. He had been maintained on losartan 50mg once daily for five years and previous routine laboratory measurements revealed a baseline platelet count of 248.0×109 cells/L.The patient began receiving an oral prednisone taper and his platelet count returned to a stable value of >200×109 cells/L. Because there was no other probable cause, he was thought to have developed immune thrombocytopenia from the increased losartan dose. Losartan was discontinued and one week later he was switched to valsartan 160mg once daily.Forty-seven days after starting valsartan, the patient presented once again to the emergency room with intermittent epistaxis and gingival bleeding while brushing his teeth of two weeks duration. Laboratory measurement revealed a platelet count of 37×109 cells/L. Valsartan was held and another prednisone taper was initiated. The patient’s platelet count recovered upon valsartan discontinuation and in four weeks, his platelet count improved to 214×109 cells/L.ConclusionsA 61-year-old Caucasian man developed immune thrombocytopenia after an increase in losartan dose and developed immune thrombocytopenia again after he was switched to valsartan.

Nonglycemic Outcomes of Antidiabetic Medications

IN BRIEF The number of medications used to treat diabetes has increased dramatically in the past 15 years. With so many options that have shown significant A1C improvement, it is important to consider side effects, precautions, and additional benefits these agents may offer. This article is a review of some of the most compelling literature available on the nonglycemic benefits of sulfonylureas, thiazolidinediones, biguanides, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium–glucose cotransporter 2 inhibitors. Other classes of antihyperglycemic agents, such as dopamine agonists, meglitinides, and amylin agonists, are not discussed in this article.

The rise of biosimilars: How they got here and where they are going

Biosimilars have become a subject of great interest in the past few years. The European Union and the United States are seeing an increasing number of biosimilar applications and approvals. The development of a biosimilar is significantly more complex and costly than a small molecule generic product. In the European Union, there has been a wider use of these medications compared to the United States. More biosimilars are gaining approval in the United States, and these products will likely alter the healthcare system in highly impactful ways. Understanding the regulatory process, the risks, and benefits will enable clinicians to be prepared and maximize the utility of these medications when they enter the market. This article introduces the concept of a biosimilar, discusses the regulatory process in the United States, and reviews the risks and benefits of these products.