Romosozumab: A Novel Injectable Sclerostin Inhibitor With Anabolic and Antiresorptive Effects for Osteoporosis.

OBJECTIVE: To review the clinical pharmacology, efficacy, and safety of romosozumab, a humanized monoclonal antibody with a novel mechanism of action for monthly injection, and its place in the management of osteoporosis. DATA SOURCES: PubMed, MEDLINE, and ClinicalTrials.gov searches (1966 to July 2020) were conducted using the keywords romosozumab and osteoporosis. STUDY SELECTION AND DATA EXTRACTION: Published phase 2 and 3 clinical trials and 2 meta-analyses in patients with osteoporosis were included. DATA SYNTHESIS: Romosozumab increased bone mineral density (BMD) at the lumbar spine (12.1%-13.3%), femoral neck (2.2%-5.9%), and total hip (2.5%-6.9%) in patients with osteoporosis. After 12 months, romosozumab provided greater BMD gains at the lumbar spine and hip than teriparatide. However, teriparatide is likely to further increase BMD if continued for up to 24 months. In postmenopausal women at a high fracture risk, 1 year of romosozumab followed by 1 year of alendronate resulted in lower vertebral, nonvertebral, clinical, and hip fractures than alendronate alone for 2 years. Although absolute event rates were low, serious cardiovascular and cerebrovascular events were numerically higher in 2 clinical trials when compared with alendronate (2.5% vs 1.9%, respectively) and placebo (4.9% vs 2.5%, respectively). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review discusses the place in therapy for romosozumab in osteoporosis management as a novel agent. CONCLUSIONS: Romosozumab offers an alternative for patients with a high risk of osteoporotic fractures. Clinicians should avoid romosozumab in patients with a history of myocardial infarction or stroke in the past 12 months.

The use of a disease state simulation assignment increased students' empathy and comfort with diabetes nutrition counseling.

BACKGROUND AND PURPOSE: To determine if a disease state simulation assignment increases empathy, comfort, and knowledge in diabetes nutrition counseling. EDUCATIONAL ACTIVITY AND SETTING: One-hundred forty students completing ambulatory care experiential rotations over two academic years were invited to participate in the study. Students in the intervention group completed an empathy assignment, which involved developing and following a diet plan appropriate for a patient with diabetes followed by a reflection of their experiences. Students completed a pre- and post-intervention survey assessing empathy, comfort with counseling, and knowledge of diabetes nutrition. FINDINGS: Fifty-three students (31 in the intervention, 22 in the non-intervention group) completed the pre- and post-survey and provided informed consent. Empathy scores on the Kiersma Chen Empathy Scale (range 15-105) improved by 6.4 points in students in the intervention group compared to a decline of 1.2 in students in the non-intervention group (p = 0.045). Comfort in counseling on a diabetes diet, measured on a 10-point scale, increased significantly more in students completing the empathy assignment (4.7 vs 3.5; p = 0.044). Knowledge (0-100%) improved by 9.7% and 8.6% in the intervention and non-intervention groups, respectively (p = 0.859). DISCUSSION: Similar to other studies using disease state simulations, the findings of this study show increased confidence in counseling and empathy. Given that the assignment used in this study is more specific to nutrition counseling, its use may be most helpful in settings where pharmacists are responsible for diabetes nutrition counseling. SUMMARY: Implementation of a similar assignment could be considered for experiential rotations with nutrition counseling.

Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used in combination with insulin to manage type 2 diabetes mellitus, and four agents are currently approved for this indication: exenatide, liraglutide, dulaglutide, and albiglutide. The distinctive properties of GLP-1 RAs-potential hemoglobin A1c (A1C) reduction, weight loss, potential to reduce insulin doses, and lower hypoglycemia risk-have made these agents potential treatment options for patients with type 1 diabetes mellitus (T1DM) as well. These positive effects are due to glucose-dependent insulin secretion, reduced glucagon secretion, increased satiety, and delayed gastric emptying. Patients with T1DM are unable to suppress glucagon during meals, which contributes to postprandial hyperglycemia and may be improved with GLP-1 therapy. In this review, we evaluated the available literature on the clinical efficacy and safety of GLP-1 RAs in patients with T1DM. We conducted a search of the PubMed (1966-May 2016) and Ovid (1946-May 2016) databases. Abstracts presented at the scientific and clinical sessions of the American Diabetes Association and the American Association of Clinical Endocrinologists were also searched. The references of the published articles were also reviewed to identify additional studies appropriate for inclusion. All identified articles published in English were evaluated. Studies were included if they evaluated the clinical use or safety of GLP-1 RAs in patients with T1DM. Twelve studies were included, with four evaluating exenatide, one evaluating exenatide extended release, and seven evaluating liraglutide. Both exenatide and liraglutide showed significant reductions in hemoglobin A1C, plasma glucose concentration, body weight, and insulin doses when administered to patients with T1DM already receiving insulin therapy, without increasing the occurrence of hypoglycemia. Adverse effects were mostly gastrointestinal in nature but were mild and transient. Patients who may benefit most are those experiencing adverse effects from insulin, those not at their A1C goal but hypoglycemia prevents insulin titration, and those who may benefit from weight loss.

Metformin-Induced Fixed-Drug Eruption Confirmed by Multiple Exposures.

BACKGROUND: A fixed-drug eruption (FDE) is a reaction characterized by cutaneous lesions that appear due to exposure to a particular drug. Barbiturates, carbamazepine, sulfamethoxazole, and tetracyclines have all been associated with causation of FDEs. Although these drugs are more commonly associated with FDEs, any introduction of a medication has the potential to result in a FDE. Metformin, a commonly used medication to improve glycemic control, has been reported to cause dermatologic reactions in some case reports, but only a single previously documented case report discusses the potential of metformin-associated FDE. CASE REPORT: We describe a 56-year-old woman who developed a FDE with multiple exposures to metformin. Upon each exposure, small, round, erythematic lesions developed on the palms of the hands and soles of the feet; these lesions resolved each time after discontinuation of metformin. According to the Naranjo scale, there is a definite association between metformin and FDE in this case (score of 8). CONCLUSIONS: This report contributes to the limited documented literature on metformin-induced FDE. Clinicians should be made aware of possible FDEs associated with this commonly used medication.

Assessing Adherence to Insulin Initiation Recommendations at a Suburban Family Medicine Clinic.

The American Diabetes Association recommends insulin initiation when A1c ≥10%. The aim of this study was to determine adherence to insulin initiation in patients with an A1c ≥10% at an outpatient family medicine clinic. The secondary objectives were to determine whether initiation of insulin within 3 weeks of an A1c ≥10% increased the rate or decreased the time to achieve an A1c <7% and to determine whether pharmacist involvement increased the rate of reaching an A1c <7%. This institutional review board-approved, retrospective, observational, cohort study identified 120 patients with type 2 diabetes mellitus and an A1c ≥10% in 2014. Patients already receiving insulin or those without a follow-up A1c were excluded. Study outcomes included proportion of patients receiving insulin therapy within 3 weeks of A1c >/=10%, rate of meeting A1c <7%, time to reach A1c <7%, and proportion of patients meeting with a pharmacist. Fifty-five patients with a mean age of 55 years, a mean duration of diabetes of 6.4 years, and a mean baseline A1c of 11.7% met the inclusion criteria. Most patients were receiving no therapy (29%), monotherapy (27%), or dual therapy (29%) at baseline. Insulin was initiated in 5 patients (9.1%, P < 0.05) within 3 weeks of the qualifying A1c. Another 5 patients (P < 0.05) received insulin at some point during the study. An A1c <7% was achieved in 35.6% of patients not receiving insulin, 20% of patients receiving early insulin, and no patients who received insulin after 3 weeks. The mean time to A1c <7% was 6 months for patients not on insulin and 3 months for those receiving early insulin. Thirty-three percent of patients who met with a pharmacist reached an A1c <7% compared with 30% of patients who did not. Adherence to insulin initiation guidelines and rate of achieving A1c <7% in patients with A1c ≥10% is low. Increasing pharmacy involvement may increase the rate of reaching goal A1c.

Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus.

Glucagon-like peptide-1 (GLP-1) has been evaluated for use in the treatment of type 2 diabetes mellitus (T2DM) due to its role in glucose regulation. Four GLP-1 receptor agonists (RAs) are currently indicated for T2DM in the USA. Exenatide and liraglutide are short-acting and require twice-daily and daily dosing, respectively. Two longer acting agents, exenatide long-acting release (LAR) and albiglutide, were formulated to allow for once-weekly dosing. All four GLP-1 RAs have demonstrated reductions in hemoglobin A1c, fasting blood glucose, and body weight both as monotherapy and in combination with first- and second-line diabetes agents including metformin, sulfonylureas, thiazolidinediones, and insulin. Greater glycemic control was seen with liraglutide compared with the other GLP-1 treatment options; however, the two long-acting agents were superior to exenatide twice daily. All agents were well tolerated with most adverse events being mild or moderate in nature. The most common adverse event was transient nausea which typically resolved 4-8 weeks after treatment initiation. Long-acting agents had lower rates of nausea but an increased incidence of injection site reactions. Trials have suggested GLP-1 RAs may improve cardiovascular risk factors including blood pressure, lipid parameters and inflammatory markers. Future trials are needed to confirm the clinical outcomes of these agents. Overall, GLP-1 RAs will provide benefit for patients with T2DM intolerable to or not reaching glycemic goals with first-line agents, especially in patients in need of weight loss.

Pharmacological management of obesity in pediatric patients.

OBJECTIVE: To review current evidence of pharmacological options for managing pediatric obesity and provide potential areas for future research. DATA SOURCES: A MEDLINE search (1966 to October 2014) was conducted using the following keywords: exenatide, liraglutide, lorcaserin, metformin, obesity, orlistat, pediatric, phentermine, pramlintide, topiramate, weight loss, and zonisamide. STUDY SELECTION AND DATA EXTRACTION: Identified articles were evaluated for inclusion, with priority given to randomized controlled trials with orlistat, metformin, glucagon-like peptide-1 agonists, topiramate, and zonisamide in human subjects and articles written in English. References were also reviewed for additional trials. DATA SYNTHESIS: Whereas lifestyle modification is considered first-line therapy for obese pediatric patients, severe obesity may benefit from pharmacotherapy. Orlistat is the only Food and Drug Administration (FDA)-approved medication for pediatric obesity and reduced body mass index (BMI) by 0.5 to 4 kg/m(2), but gastrointestinal (GI) adverse effects may limit use. Metformin has demonstrated BMI reductions of 0.17 to 1.8 kg/m(2), with mild GI adverse effects usually managed with dose titration. Exenatide reduced BMI by 1.1 to 1.7 kg/m(2) and was well-tolerated with mostly transient or mild GI adverse effects. Topiramate and zonisamide reduced weight when used in the treatment of epilepsy. Future studies should examine efficacy and safety of pharmacological agents in addition to lifestyle modifications for pediatric obesity. CONCLUSIONS: Lifestyle interventions remain the treatment of choice in pediatric obesity, but concomitant pharmacotherapy may be beneficial in some patients. Orlistat should be considered as second-line therapy for pediatric obesity. Evidence suggests that other diabetes and antiepileptic medications may also provide weight-loss benefits, but safety should be further evaluated.

Robotic guidance does not improve component position or short-term outcome in medial unicompartmental knee arthroplasty.

We performed a retrospective review in a matched group of patients on the use of robotic-assisted UKA implantation versus UKA performed using standard operative techniques to assess differences between procedures. While both techniques resulted in reproducible and excellent outcomes with low complication rates, the results demonstrate little to no clinical or radiographic difference in outcomes between cohorts. Average operative time differed significantly with, and average of 20 minutes greater in, the robotic-assisted UKA group (P=0.010). Our minimal clinical and radiographic differences lend to the argument that it is difficult to justify the routine use of expensive robotic techniques for standard medial UKA surgery, especially in a well-trained, high-volume surgeon. Further surgical, clinical and economical study of this technology is necessary.

The clinical efficacy and safety of sodium glucose cotransporter-2 inhibitors in adults with type 2 diabetes mellitus.

The use of currently available antihyperglycemic agents can be limited by contraindications; cost; renal and hepatic dosage adjustments; dosing schedules; and adverse effects such as gastrointestinal upset, weight gain, and hypoglycemia. These limitations have led the pharmaceutical industry to identify and pursue alternative therapies. Sodium glucose cotransporter-2 (SGLT-2) inhibitors belong to a new class of diabetes drugs and have a novel mechanism of action. These agents are unique in that they increase glucose excretion, independent of insulin secretion, by inhibiting the renal reabsorption of glucose, inducing glycosuria. To summarize the current evidence for SGLT-2 inhibitor therapy, we reviewed abstracts and published data from human trials evaluating the efficacy and safety of dapagliflozin, canagliflozin, and empagliflozin through February 2013. Data from these trials suggest that SGLT-2 inhibitors are able to lower hemoglobin A1c and fasting blood glucose when used as either monotherapy or combination therapy. Cardiometabolic benefits included a reduction in systolic blood pressure, reduction in triglycerides, and weight loss of up to 3 kg. Common and serious adverse effects including infections, cancer, and pollakiuria were identified and reviewed. Although these agents have generally demonstrated efficacy, the adverse effects associated with dapagliflozin have caused a delay in its regulatory approval. Continued research in this area will determine the risk:benefit ratio of SGLT-2 inhibitor therapy.

The clinical use of denosumab for the management of low bone mineral density in postmenopausal women.

Osteoporosis is a leading cause of debility and declining quality of life in postmenopausal women worldwide. Treatment of osteoporosis has been ubiquitous throughout the developed world since the mid-1990s, most notably with the introduction of bisphosphonates in 1995. Nonetheless, the incidence of hip fractures increased by 25% between 1990 and 2000, despite advances in osteoporosis therapy. Studies indicate that bone density increases over the first 3 years of bisphosphonate therapy and then plateaus or perhaps even declines, placing these patients at greater risk of fracture. Since hip fractures are associated with increased morbidity, mortality, and increased cost of health care, improvements in treating osteoporosis are critical. Denosumab is a novel monoclonal antibody targeted against the receptor activator of nuclear factor-κB ligand (RANKL) that inhibits osteoclast activity. Initial data suggest that denosumab increases bone mineral density for greater than 3 years. Of greater importance, denosumab has been shown to decrease vertebral fractures by 68%, nonvertebral fractures by 19%, and hip fractures by 42% for at least 36 months. Data also indicate that the safety profile of denosumab is equivalent to other drugs used in osteoporosis management, but potential risks of immunosuppression and cancer have been hypothesized.