Lomitapide and mipomersen: novel lipid-lowering agents for the management of familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused primarily by mutations in the low-density lipoprotein receptor gene. Familial hypercholesterolemia is characterized by exceedingly high levels of low-density lipoprotein cholesterol (LDL-C) and subsequent premature coronary heart disease. Homozygous FH (HoFH) is less prevalent, but more severe, than heterozygous FH. Current treatment options include dietary therapy, lipid-lowering agents (eg, statins), and/or LDL-C apheresis. PURPOSE: Despite the available treatment options, patients with FH rarely attain treatment goals. This review will focus on 2 novel agents, lomitapide and mipomersen, with recently approved US Food and Drug Administration (FDA) labeling for use in patients with HoFH. CONCLUSIONS: Lomitapide and mipomersen are 2 agents with novel mechanisms of action and the ability to significantly lower LDL-C, apolipoprotein B, and non-high-density lipoprotein cholesterol levels. A black box warning exists for lomitapide and mipomersen regarding the risk for transaminase elevations and hepatic steatosis. Furthermore, these agents are currently restricted for use only in patients with HoFH and have been required by the FDA to participate in a Risk Evaluation and Mitigation Strategy. CLINICAL IMPLICATIONS: These new agents offer additional treatment options for clinicians managing patients with HoFH, but it remains uncertain whether lomitapide and mipomersen will gain FDA approval for use in patients with heterozygous FH or in the general population. Cost and concern for the risk for hepatotoxicity will remain limiting factors to these agents being more widely used.

Feasibility and efficacy of a nurse practitioner-and pharmacist-led hypertension clinic.

ABSTRACT: Hypertension (HTN) affects over one third of adults in the United States. Blood pressure (BP) management and patient education are provided by physicians, advanced practice clinicians, pharmacists, and nurses. In the traditional medical/clinic model, physicians have provided and directed HTN care. However, advanced practice nurses and pharmacists are also well trained and positioned to manage HTN. The purpose of this study was to explore the feasibility of an HTN clinic, led by a nurse practitioner (NP) and PharmD, specifically analyzing if targeted HTN can be achieved in this setting. Registry data were used to analyze the initial and the most recent visit BP levels in patients who were seen in an NP/PharmD-led HTN clinic. Measures of central tendency and differences between initial and most recent visit were also compared. A total of 46 patients were included in this analysis. Data showed that there was no statistically significant difference in the first visit (144/86) and the most recent visit (138/84) BP ( p = .26), but that there was a clinical trend in decreasing BP as well as narrowing of BP ranges and interquartile ranges between visit. The NP/PharmD-led clinic is feasible and can help lower BP and narrow ranges toward targeted BP.

Evaluation of Vitamin B12 Monitoring in Veterans With Type 2 Diabetes on Metformin Therapy.

BACKGROUND: Studies have shown an association between metformin use and vitamin B12 deficiency. Since 2017, the American Diabetes Association (ADA) Standards of Medical Care in Diabetes Guideline has included a recommendation for periodic vitamin B12 measurements in metformin-treated patients, especially those with anemia or peripheral neuropathy. OBJECTIVE: To determine the overall incidence and impact of the ADA Guideline on vitamin B12 monitoring in a veteran population on long-term metformin therapy. METHODS: Retrospective chart review was performed for patients on metformin who started therapy prior to 2005 at the VA North Texas Health Care System (VANTXHCS). The primary outcome was the proportion of patients with at least 1 vitamin B12 level drawn during 2016 versus 2018. Metformin dose and duration, vitamin B12 supplementation, and incident neuropathy prescriptions or diagnosis were also analyzed. RESULTS: Of 394 patients included for the primary outcome, 136 (34.5%) had at least 1 vitamin B12 level in 2016 versus 198 (50.3%) patients in 2018 (odds ratio: 1.94, P < .001). Of the 394 patients, 157 were diagnosed with neuropathy or prescribed a medication for neuropathy without a vitamin B12 level in the previous year or with a low level that was not supplemented. CONCLUSION: Vitamin B12 monitoring significantly increased between 2016 and 2018, aligning with the release of the 2017 ADA guidelines. However, a large proportion of patients were identified who were diagnosed with or treated for neuropathy without adequate vitamin B12 monitoring.

Weight effects of antidiabetic agents.

INTRODUCTION: Obesity and diabetes are on the rise, which remains a continuous health concern worldwide. It is important to consider weight effects of antidiabetic agents prior to initiation as different antidiabetic agents impact weight differently. Areas covered: New agents to treat diabetes, glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors, have emerged over recent years that have been shown to result in weight reduction. Unfortunately, other antidiabetic medications used can cause weight gain such as with insulin, sulfonylureas, and thiazolidediones while some remain weight neutral (metformin and dipeptidyl peptidase-4 inhibitors). The weight effects of these antidiabetic medications described are from select relevant guidelines, clinical trials, reviews, and meta-analysis found through PubMed and Ovid databases up to July 2017. Expert commentary: This article summarizes the current evidence available on the weight effects of these agents in patients with diabetes. Evaluating potential risks, such as weight gain, with potential benefits, such as improvement in glycemic control, will help with designing optimal therapeutic diabetes regimens.

Clinical Inquiry: Do ACE inhibitors or ARBs help prevent kidney disease in patients with diabetes and normal BP?

Yes for angiotensin-converting enzyme (ACE) inhibitors, no for angiotensin receptor blockers (ARBs). A 2011 meta-analysis of 5 RCTs (total 2975 patients) that compared ACE inhibitor therapy with placebo in diabetic patients without hypertension and albuminuria found that ACE inhibitors reduced the risk of new-onset microalbuminuria or macroalbuminuria by 18% (relative risk [RR]=0.82; 95% confidence interval [CI], 0.73-0.92).

Pharmacological management of obesity in patients with type 2 diabetes.

INTRODUCTION: Obesity is a growing health concern worldwide. Multiple guidelines are available to clinicians to help guide treatment of obesity. Areas covered: In their 2016 update, the American Diabetes Association included recommendations for the use of pharmacological agents in the treatment of obesity in patients with concurrent diabetes. Five agents have been approved by the Food and Drug Administration and are recommended by guidelines for the long-term treatment of obesity: orlistat, lorcaserin, phentermine/topiramate ER, naltrexone/bupropion, and liraglutide. Expert commentary: This article summarizes the current evidence available on the use of these agents in patients with diabetes.