Stephen Brunton

Differences between Dietary Supplement and Prescription Drug Omega-3 Fatty Acid Formulations: A Legislative and Regulatory Perspective

The medical management of many diseases and conditions can include either restriction or provision of specific essential nutrients. When such nutrients are needed, there are often both prescription and nonprescription products available, as in the case of nicotinic acid or omega-3 fatty acids. Although they may seem to contain similar ingredients, there may be important differences between the prescription and dietary-supplement preparations. The manufacturing of prescription pharmaceutical products is regulated by the US Food and Drug Administration (FDA), which mandates standards for consistency and quality assurance. Dietary supplements are available to consumers under the provisions of the Dietary Supplement Health and Education Act of 1994, for which the FDA has the burden of proving a dietary supplement is harmful rather than requiring the manufacturer prove that the supplement is safe. Consumers and medical professionals should be aware of the important qualitative and quantitative differences between the FDA-approved prescription formulations and dietary supplements, particularly when an essential nutrient is part of the medical management of a disease or condition.

Patient use of dietary supplements: a clinician's perspective

ABSTRACT Background: The estimated prevalence of dietary-supplement use among US adults was 73% in 2002. Appropriate use of dietary supplements within the paradigm of evidence-based medicine may be a challenge for medical doctors and non-physician clinicians. Randomized, controlled, clinical trial data, which are considered the gold standard for evidence-based decision making1, are lacking. Standardized guidelines for the use of dietary supplements are lacking, and dietary supplements can bear unsupported claims. Objectives: This article is intended to review clinically-relevant issues related to the widespread use of dietary supplements, with emphasis on regulatory oversight and safety. Methods: Review articles and clinical trial articles published up until December 2007 were selected based on a search of the MEDLINE electronic database using PubMed. The Food and Drug Administration (FDA) Website was also used as a resource. We used the search terms dietary supplement(s), vitamin supplements, mineral supplements, and Dietary Supplement and Health Education Act. Articles discussing dietary supplements and their regulation, prevalence of use, prescription and nonprescription formulations, and/or adverse events were selected for review. Articles discussing one or more of these topics in adults were selected for inclusion. Results: New FDA regulations require dietary-supplement manufacturers to evaluate the identity, purity, strength, and composition of their products. However, these regulations are not designed to demonstrate product efficacy and safety, and dietary-supplement manufacturers are not required to submit efficacy and safety data to the FDA prior to marketing. Product contamination and/or mislabeling may undermine the integrity of dietary-supplement formulations. Conclusions: The use of dietary supplements may be associated with adverse events. Although there are new regulatory requirements for dietary supplements, these products will not require FDA approval or submission of efficacy and safety data prior to marketing under the new regulation. A limitation to the literature used for this review is the lack of prospective, randomized clinical trials on the safety and efficacy of dietary supplements. Clinicians should be aware of all the dietary supplements that their patients consume, and help their patients make informed decisions appropriate to their medical care.

Recent developments in the management of overactive bladder: focus on the efficacy and tolerability of once daily solifenacin succinate 5 mg

ABSTRACT Background: Overactive bladder (OAB) is a highly prevalent symptom complex that may be extremely distressing to the patient, and can be associated with co-morbidities and reduced quality of life (QoL). One of the major pathophysiological causes of OAB is overactivity of the detrusor muscle, mediated via muscarinic receptors in the bladder. Urgency is the defining symptom of OAB, yet a significant proportion of patients also suffer from incontinence, which is the most distressing symptom to the patient. As such, restoration of continence should be a primary treatment goal. However, effective treatments should also impact on the other key symptoms of OAB, such as micturition frequency and urgency. Non-pharmacologic interventions to treat OAB can be effective but require patients to be highly motivated. In terms of pharmacologic therapy, treatment with an antimuscarinic agent is the mainstay of current therapy. Solifenacin succinate is a once-daily oral antimuscarinic for the treatment of OAB. The recommended dose is 5 mg once daily and can be increased to 10 mg once daily if 5 mg is well tolerated. Objectives: This paper reviews clinical experience with solifenacin 5 mg in patients with OAB as this is the recommended dose according to FDA product labeling. Findings: In Phase 3 studies, based on data captured in 3-day micturition diaries, greater than half of patients who were incontinent at baseline no longer reported experiencing incontinence episodes after 12 weeks of double-blind treatment with solifenacin 5 mg. Furthermore, compared with placebo, solifenacin treatment resulted in statistically significant reductions in incontinence episodes, micturition frequency and urgency episodes, with significant increases in volume voided (based on an analysis of key symptom outcomes in two pooled Phase 3 studies presented here). The most common treatment-related adverse events were expected anticholinergic side effects (dry mouth, constipation, and blurred vision), and these were generally mild to moderate. Discontinuation rates due to adverse events in the treatment and placebo groups were comparable. Conclusion: Solifenacin 5 mg was found to be efficacious and had an acceptable tolerability profile in patients with OAB in these trials and this treatment may provide QoL benefits to patients.

Differentiating prescription omega-3-acid ethyl esters (P-OM3) from dietary-supplement omega-3 fatty acids

ABSTRACT Background: A reliable means of treating hypertriglyceridemia is the use of large doses of the omega‑3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Modest levels of EPA and DHA may be obtained from food, particularly fatty fish. Objectives: This article is intended to review clinically relevant differences between dietary-supplement omega‑3 fatty acids and prescription omega‑3-acid ethyl esters (P-OM3). Methods: PubMed and the Food and Drug Administration (FDA) Website were searched for articles published between 1995 and 2007 that contained the terms fish oil, fatty acids, n-3 fatty acids, omega fatty acids, docosahexaenoic acid, or eicosapentaenoic acid. Articles discussing sources, recommended intake, and differences among various formulations of omega‑3 fatty acids were selected for review. A limitation to this review is the lack of head-to-head clinical trials using P‑OM3 and dietary-supplement omega‑3 fatty acids. Results: Many types of nonprescription dietary supplements of omega‑3 fatty acids are available; however, the efficacy, quality, and safety of these products are open to question because they are not regulated by the same standards as pharmaceutical agents. P‑OM3 is the only omega‑3 fatty acid product (Omacor* capsules) approved by the US FDA available in the United States as an adjunct to diet to reduce very high (≥ 500 mg/dL) triglyceride levels in adult patients. Conclusions: P‑OM3 can be used with confidence by practitioners who want to provide therapeutic doses of omega‑3 fatty acids in a preparation that has been documented to be both safe and effective.

A look into the future: improving diabetes care by 2015

Abstract Insulin initiation, which was traditionally the province of specialists, is increasingly undertaken by primary care. However, significant barriers to appropriate and timely initiation still exist. Whilst insulin is recognized as providing the most effective treatment in type 2 diabetes, it is also widely considered to be the most challenging and time consuming. This editorial identifies that the organization of existing healthcare services, the challenges faced by patients, and the treatments themselves contribute to suboptimal insulin management. In order to improve future diabetes care, it will be necessary to address all three problem areas: (1) re-think the best use of existing human and financial resources to promote and support patient self-management and adherence to treatment; (2) empower patients to participate more actively in treatment decision making; and (3) improve acceptance, persistence and adherence to therapy by continuing to refine insulin therapy and treatment regimens in terms of safety, simplicity and convenience. The principles discussed are also applicable to the successful management of any chronic medical illness.

Hypoglycemic Potential of Current and Emerging Pharmacotherapies in Type 2 Diabetes Mellitus

Abstract Intensive glycemic control can reduce the risk of microvascular complications in patients with type 2 diabetes mellitus (T2DM). However, hypoglycemia induced by diabetes medications is recognized as a major limiting factor in the attainment of glycemic goals. Mild hypoglycemia is relatively common in patients with T2DM, and the prevalence of severe hypoglycemia increases with insulin treatment and can approach the prevalence seen in patients with type 1 diabetes. Mild hypoglycemia and the fear of hypoglycemia can have a substantial impact on the physical, mental, social, and economic well–being of patients with T2DM. Severe hypoglycemia is more serious and may be associated with an increased risk of dementia, cardiovascular events, and death. Insulin and insulin secretagogue therapies (eg, sulfonylureas and meglitinides) are the major causes of hypoglycemia in patients with T2DM. Other diabetes drugs, such as metformin, when used as monotherapy, have a low risk of hypoglycemia. Emerging experimental therapies, such as activators of the free fatty acid receptor 1, G protein–coupled receptor 119 agonists, glucokinase activators, inhibitors of 11β-hydroxysteroid dehydrogenase type 1, and sodium–glucose co–transporter 2 inhibitors, some of which have mechanisms of action consistent with a potential low risk of hypoglycemia, may help patients with T2DM achieve improved glycemic control.

Patient perceptions of insulin detemir as reported through patient telephone surveys

ABSTRACT Objectives: To examine patient-reported perceptions of insulin detemir (Levemir†) as treatment for diabetes and report information back to prescribing physicians. Methods: This cross-sectional survey with a convenience population involves physicians identifying patients appropriate for this treatment and providing them with study information. Patients voluntarily responded to a baseline survey prior to medication use and surveys at approximately 30 and 60 days following treatment initiation using interactive voice response (IVR) technology. Questions were designed by the medical group on the study team to measure patients’ perceptions regarding blood sugar control, confidence in avoiding symptoms and medication satisfaction with insulin detemir. Questions were not drawn from a tested survey instrument, but do maintain face validity. Prescribing physicians received an individual report summarizing the patients responses. Results: In total, 586 adults completed the study. Average age was 59 years; 64% female. After an average of 35 days and 72 days using insulin detemir, patients could more easily judge blood sugar levels (n = 586; average 6.6 and 7.0 out of 10 (10 = much easier) at each follow-up, respectively) and keep good blood sugar control (n = 586; 6.7 and 7.0). With insulin detemir, patients who used a prior insulin (n = 414) felt more confident about avoiding symptoms of hypoglycemia with an average rating of 6.8 out of 10 after the first month and 7.1 out of 10 (10 = much more confident) after the second month. They (n = 414) also felt more confident in avoiding low blood sugars at night with average ratings of 7.3 after both the first and second months with insulin detemir. Thirty-one percent of the prior insulin users (n = 414) also reported weight loss, 58% reported no change, 11% gained weight after the second month with insulin detemir. Satisfaction with insulin detemir among all patients (n = 586) averaged 7.9 out of 10 at both months 1 and 2. Conclusions: With insulin detemir, patients felt more confident about managing blood sugar levels, tended not to gain weight, and were quite satisfied. The authors recognize that the results are not generalizable to or representative of all patients using insulin detemir due to potential patient selection bias. In addition, the results reflect patients’ self-reported impressions which were not confirmed through any objective clinical measures. However, the individual patient data collected through the surveys can help physicians monitor patients’ perceptions and promote discussions about treatment with patients.

Early intervention to achieve optimal outcomes in type 2 diabetes: a case presentation.

Type 2 diabetes mellitus (DM) is a progressive disease characterized by insulin resistance and impaired insulin secretion. To compensate for these metabolic dysfunctions, pancreatic beta-cells begin to overproduce insulin; however, it is this compensatory mechanism that eventually results in beta-cell exhaustion, impaired insulin secretion, and relative insulin deficiency. The metabolic abnormalities associated with diabetes also contribute to vascular dysfunction and an increased risk of coronary heart disease. Among patients with type 2 DM, cardiovascular disease, particularly macrovascular disease, is the primary cause of mortality, accounting for 55% of deaths. Management of the disease, therefore, must address all of the contributing factors, including a sedentary lifestyle and diet that contribute to overweight/obesity, and comorbidities such as hypertension and dyslipidemia. In this paper, we present a case study based on actual clinical experience to illustrate an evidence-based rationale for early and aggressive intervention for patients with type 2 DM, including lifestyle modification, oral antidiabetic agents, and insulin.

A comprehensive approach to Parkinson's disease. How to manage fluctuating motor and nonmotor symptoms.

PREVIEW Because of their close rapport with patients and their families, primary care physicians are in a unique position to provide comprehensive care for patients with Parkinsons disease. In this environment, they can monitor changes in motor status and prescribe drugs either alone or in consultation with neurologists and other specialists. Primary care physicians also can treat debilitating nonmotor symptoms of Parkinsons disease, such as chronic pain, autonomic dysfunction, mood disorders, sleep disturbances, and cognitive impairment. In this article, Dr Brunton describes the complex presentation of this disease, appropriate drug therapy, drug side effects, and neurosurgical techniques that may be used should drugs fail.

Role of Emerging Insulin Technologies in the Initiation and Intensification of Insulin Therapy for Diabetes in Primary Care.

In Brief This article explores some of the reasons for the delay in insulin initiation in primary care and evaluates new approaches to insulin therapy that may address these barriers and, therefore, improve insulin use by primary care providers.