Obesity Management: Clinical Review and Update of the Pharmacologic Treatment Options.

The toolbox of medications available for medical weight management is more robust than ever and includes a wide variety of mechanisms of actions and options for patients.

Diagnosis and treatment of patients with thyroid cancer.

BACKGROUND: Thyroid cancer is the most common malignancy of the endocrine system, representing 3.8% of all new cancer cases in the United States and is the ninth most common cancer overall. The American Cancer Society estimates that 62,450 people in the United States will be diagnosed with thyroid cancer in 2015, and 1950 deaths will result from the disease. OBJECTIVE: To review the current approach to the diagnosis and treatment of patients with thyroid cancer. DISCUSSION: Over the past 3 decades, there has been a dramatic increase in the number of people diagnosed with thyroid cancer, which may be attributable to the wide use of imaging studies, including ultrasounds, computed tomography, magnetic resonance imaging, and positron emission tomography scans that incidentally detect thyroid nodules. Thyroid cancer is divided into several main types, with papillary thyroid cancer being the most common. The treatment options for patients with thyroid cancer include the surgical removal of the entire thyroid gland (total thyroidectomy), radioactive iodine therapy, and molecular-targeted therapies with tyrosine kinase inhibitors. This article summarizes the diagnosis and treatment of thyroid cancer, with recommendations from the American Thyroid Association regarding thyroid nodules and differentiated thyroid cancer. Recently approved drugs and treatment trends are also explored. CONCLUSION: The prognosis and treatment of thyroid cancer depend on the tumor type and its stage at the time of diagnosis. Many thyroid cancers remain stable, microscopic, and indolent. The increasing treatment options for patients with thyroid cancer, including therapies that were recently approved by the US Food and Drug Administration, have kept the mortality rate from this malignancy low, despite the increase in its incidence. Early diagnosis and appropriate treatment can improve prognosis and reduce mortality.

SGLT2 Inhibitors for Type 2 Diabetes Mellitus Treatment.

SGLT2 inhibitors are plausible second-line drugs that provide powerful additional A1c-lowering effects while inducing weight loss without hypoglycemia.

Serum 25-hydroxyvitamin D concentrations in relation to cardiometabolic risk factors and metabolic syndrome in postmenopausal women.

BACKGROUND: Low concentrations of serum 25-hydroxyvitamin D [25(OH)D] may be associated with cardiometabolic disorders; however, little is known about their relation to intermediate metabolic and lipid markers. OBJECTIVE: We investigated the relation of serum 25(OH)D concentrations to fasting insulin, glucose, dyslipidemia, adiposity, and prevalent metabolic syndrome. DESIGN: We conducted this cross-sectional analysis in 292 postmenopausal women aged 50-79 y in the Women's Health Initiative Calcium-Vitamin D (WHI-CaD) trial. Data were collected from 3 nested case-control studies that measured baseline serum 25(OH)D concentrations. Inverse probability weighting was used to approximate parameter estimates for the WHI-CaD population. RESULTS: In weighted linear regression models adjusted for age, race-ethnicity, month of blood draw, region, case-control status, smoking, alcohol, physical activity, and history of cardiometabolic risk factors, there was an inverse association of serum 25(OH)D with adiposity [body mass index (BMI): ß = -1.12 ± 0.30, P = 0.0002; waist circumference: ß = -3.57 ± 0.49, P < 0.0001; waist-hip ratio: ß = -0.01 ± 0.002, P < 0.0001], triglycerides (ß = -0.10 ± 0.02, P < 0.0001), and triglyceride:HDL-cholesterol ratio (ß = -0.11 ± 0.03, P = 0.0003). The multivariable-adjusted odds ratio for metabolic syndrome for the highest (≥52 nmol/L) compared with the lowest (<35 nmol/L) tertile of serum 25(OH)D concentrations was 0.28 (95% CI: 0.14, 0.56). Significant associations remained after adjustment for BMI. We observed no significant associations with LDL cholesterol, HDL cholesterol, insulin, glucose, homeostatic model assessment of insulin resistance (HOMA-IR), or homeostatic model assessment of ß cell function (HOMA-ß). CONCLUSION: Higher serum 25(OH)D concentrations may be inversely associated with adiposity, triglycerides, triglyceride:HDL-cholesterol ratio, and metabolic syndrome but are not associated with LDL and HDL cholesterol, insulin, glucose, HOMA-IR, or HOMA-ß in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611.

Current therapies and emerging drugs in the pipeline for type 2 diabetes.

BACKGROUND: Diabetes is a global epidemic that affects 347 million people worldwide and 25.8 million adults in the United States. In 2007, the total estimated cost associated with diabetes in the United States in 2007 was $174 billion. In 2009, $16.9 billion was spent on drugs for diabetes. The global sales of diabetes pharmaceuticals totaled $35 billion in 2010, and these are expected to rise to $48 billion by 2015. Despite such considerable expenditures, in 2000 only 36% of patients with type 2 diabetes in the United States achieved glycemic control, defined as hemoglobin A1c <7%. OBJECTIVE: To review some of the most important drug classes currently in development for the treatment of type 2 diabetes. DISCUSSION: Despite the 13 classes of antidiabetes medications currently approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes, the majority of patients with this chronic disease do not achieve appropriate glycemic control with these medications. Many new drug classes currently in development for type 2 diabetes appear promising in early stages of development, and some of them represent novel approaches to treatment, with new mechanisms of action and a low potential for hypoglycemia. Among these promising pharmacotherapies are agents that target the kidney, liver, and pancreas as a significant focus of treatment in type 2 diabetes. These investigational agents may potentially offer new approaches to controlling glucose levels and improve outcomes in patients with diabetes. This article focuses on several new classes, including the sodium-glucose cotransporter-2 inhibitors (which are furthest along in development); 11beta-hydroxysteroid dehydrogenase (some of which are now in phase 2 trials); glycogen phosphorylase inhibitors; glucokinase activators; G protein-coupled receptor 119 agonists; protein tyrosine phosphatase 1B inhibitors; and glucagon-receptor antagonists. CONCLUSION: Despite the abundance of FDA-approved therapeutic options for type 2 diabetes, the majority of American patients with diabetes are not achieving appropriate glycemic control. The development of new options with new mechanisms of action may potentially help improve outcomes and reduce the clinical and cost burden of this condition.

Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Despite increasing public health concerns regarding obesity, few safe and effective drug treatments are available. Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight. The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants. METHODS: Men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m(2) and uncomplicated obesity or BMI 27-45 kg/m(2) with dyslipidaemia or hypertension were eligible for enrolment in this randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the USA. Participants were prescribed mild hypocaloric diet and exercise and were randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB16), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation. Randomisation was done by use of a centralised, computer-generated, web-based system and was stratified by study centre. Co-primary efficacy endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5% or more. The primary analysis included all randomised participants with a baseline weight measurement and a post-baseline weight measurement while on study drug (last observation carried forward). This study is registered with ClinicalTrials.gov, number NCT00532779. FINDINGS: 1742 participants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, n=578; placebo, n=581). 870 (50%) participants completed 56 weeks of treatment (n=296; n=284; n=290, respectively) and 1453 (83%) were included in the primary analysis (n=471; n=471; n=511). Mean change in bodyweight was -1.3% (SE 0.3) in the placebo group, -6.1% (0.3) in the naltrexone 32 mg plus bupropion group (p<0.0001 vs placebo) and -5.0% (0.3) in the naltrexone 16 mg plus bupropion group (p<0.0001 vs placebo). 84 (16%) participants assigned to placebo had a decrease in bodyweight of 5% or more compared with 226 (48%) assigned to naltrexone 32 mg plus bupropion (p<0.0001 vs placebo) and 186 (39%) assigned to naltrexone 16 mg plus bupropion (p<0.0001 vs placebo). The most frequent adverse event in participants assigned to combination treatment was nausea (naltrexone 32 mg plus bupropion, 171 participants [29.8%]; naltrexone 16 mg plus bupropion, 155 [27.2%]; placebo, 30 [5.3%]). Headache, constipation, dizziness, vomiting, and dry mouth were also more frequent in the naltrexone plus bupropion groups than in the placebo group. A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups. Combination treatment was not associated with increased depression or suicidality events compared with placebo. INTERPRETATION: A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity. FUNDING: Orexigen Therapeutics.

Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity.

BACKGROUND: Bupropion and naltrexone are centrally active drugs that have shown potential efficacy - alone and in combination - for the treatment of obesity. OBJECTIVE: To explore the efficacy and safety of naltrexone and bupropion alone and in a novel combination drug that utilizes sustained-release (SR) formulations of both drugs and to evaluate their efficacy in promoting weight loss. The mechanisms of action of these centrally acting drugs are discussed. Preclinical and clinical studies of bupropion and naltrexone alone and in combination are reviewed. RESULTS/CONCLUSIONS: Both bupropion and naltrexone have been shown individually to induce weight loss. Bupropion has greater efficacy as monotherapy. Naltrexone SR potentiates the effects of bupropion SR; thus, this synergistic combination has the potential for additional weight loss compared to monotherapy. Current Phase III trials will yield further safety and efficacy information regarding these drugs in combination.

Medical nutrition: a comprehensive, school-wide curriculum review.

BACKGROUND: A school-wide nutrition program was established in 1982 and a required medical nutrition course (MNC) was established in 1985 at the University of Nevada School of Medicine. Emphasis was placed on developing an integrated curriculum and on using innovative methods to incorporate nutrition into the existing curriculum. OBJECTIVE: The objective of this review was to establish a baseline and make positive curricular changes to comply with the recommendations of the Liaison Committee on Medical Education for accreditation. The MNC and the nutrition curriculum were evaluated as part of this 3-y comprehensive, school-wide evaluation process. DESIGN: The MNC was invited for review (December 2004) because of its position in the curriculum (first year), special content and methods, and relation to other courses. A review team, which consisted of the Assistant Dean for Medical Education (who chaired the team), a curriculum coordinator, faculty representatives, and a medical student, was appointed. The MNC coordinator prepared a review book that included the requested documentation. The initial 3-h review meeting culminated in a formal evaluation and recommendations. Follow-up meetings at 1 mo and 1 y were scheduled. RESULTS: The review was a positive process that reaffirmed the uniqueness of the nutrition program at the University. It supported the MNC as an important part of the required curriculum. Recommendations included use of the Web, encouragement to identify new opportunities with interested faculty, and a structure to further integrate and align nutrition into existing courses. CONCLUSIONS: A positive, proactive review process supports the importance of nutrition in the medical school curriculum and encourages further integration.

Medical nutrition therapy for the treatment of obesity.

Most physicians do not have the benefit of in-house registered dietitians to facilitate patient evaluation and create treatment plans. Fortunately, with the new tools that are available to physicians and patients, energy balance can be evaluated. Then, a balanced deficit diet can be encouraged to achieve a weight management goal while maintaining healthy food intake patterns. Patients should also be counseled regarding weight maintenance diets to prevent weight gain. A low-fat diet is preferred because the patient will benefit from improved cardiac risk as a result of weight loss and a restricted saturated fat content is healthier. Other diets and approaches are acceptable if they are hypocaloric and do not negatively impact the patient's health (eg, some high-protein, high-fat diets can increase lipid levels; high-carbohydrate diets can increase triglycerides in patients who have type 2 diabetes). As patients lose weight, further increases in physical activity and exercise should be emphasized to help maintain lost weight. It is also helpful from a behavioral perspective to encourage patients to monitor their weight, food intake, and physical activity. Medical offices can support patients by providing weekly or biweekly weigh-ins to track progress and provide ongoing feedback. Patients should be reminded that the ultimate goal of any weight management program is gradual, incremental weight losses that are maintained over time. Sustainable and enjoyable changes in eating practices and physical activity patterns must be made along with a lifelong commitment to health.