Retrospective Analysis of Once-Daily Versus Twice-Daily Insulin Glargine Dosing in Noncritically Ill Individuals.

Background: Insulin is the treatment of choice for diabetes care in the hospital. There is some debate regarding the efficacy and safety of once-daily versus twice-daily insulin glargine in the hospital, particularly in the critically ill population. Objective: The purpose of this pilot study was to evaluate the efficacy and safety of insulin glargine administered as a once-daily versus twice-daily regimen in the noncritically ill population. Methods: A retrospective chart review was conducted from 1 June 2020 to 31 May 2021. Inclusion criteria were age ≥18 years and on a regimen of either once-daily or twice-daily insulin glargine for ≥72 hours during the specified time frame. The primary end point was a comparison of the number of days with all blood glucose measurements within the range of 70-180 mg/dL throughout a 24-hour period. Secondary end points included the number of hyperglycemic (>180 mg/dL) and hypoglycemic (<70 mg/dL) events that occurred in each study group. Results: Group 1 included 101 individuals who received once-daily dosing, and group 2 included 103 individuals who received twice-daily dosing. Baseline characteristics were similar between the groups except for a higher BMI at admission (P = 0.01) and a higher pre-admission A1C (P = 0.02) in group 2. No differences were found for the primary end point (P = 0.5) or for hypoglycemic (P = 0.6) or hyperglycemic (P = 0.7) events. Conclusion: There were no significant differences in efficacy or safety between once-daily and twice-daily insulin glargine in the noncritically ill population. A larger prospective study could confirm these results.

Development and Current Role of Sodium Glucose Cotransporter Inhibition in Cardiorenal Metabolic Syndrome.

ABSTRACT: Sodium-glucose cotransporter-2 inhibitors were approved as adjunct therapy for the management of type 2 diabetes and have become a high-level recommendation for this population with cardiorenal metabolic syndrome. In addition, evidence continues to grow supporting this class of medications for people with heart failure and chronic kidney disease, regardless of diabetes status. This narrative review summarizes the sodium-glucose cotransporter inhibitors for cardiorenal metabolic syndrome.

Clinical review of subcutaneous semaglutide for obesity.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this review paper is to review the efficacy and safety of subcutaneous semaglutide, marketed as Wegovy, a glucagon-like peptide-1 receptor agonist for obesity management. METHODS: A MEDLINE search (1970 to June 2021) was conducted to identify Phase 3 trials of subcutaneous semaglutide for obesity management. Published Phase 3 trials from The Semaglutide Treatment Effect in People with obesity (STEP) program were reviewed and summarized. RESULTS AND DISCUSSION: Based on four Phase 3 trials, subcutaneous semaglutide as 2.4 mg once weekly was compared in efficacy and safety among 5000 randomized participants who were overweight or had obesity. A change in body weight from baseline to end of study was the primary outcome in the STEP program. Participants who received semaglutide had a dose-dependent reduction in body weight from baseline, compared to placebo. Higher percentages of participants had 5%-10% weight reduction from baseline when receiving subcutaneous semaglutide. The patient population was mainly middle-aged female participants with Class II obesity. Additional studies are needed, especially active-comparator trials, to determine the efficacy and safety of semaglutide in a diverse patient population. WHAT IS NEW AND CONCLUSION: Subcutaneous semaglutide is another available option as adjunct therapy to lifestyle modifications for people who are overweight or have obesity based on body weight and body mass index. It resulted in more weight reduction than placebo with gastrointestinal adverse events being the most common safety concerns. Clinical utilization of subcutaneous semaglutide will be determined, as insurance coverage will be a limitation for this new medication.

Flibanserin for hypoactive sexual desire disorder in premenopausal women.

Flibanserin is a mixed 5-HT1A agonist and 5-HT2A antagonist for treatment of premenopausal women with hypoactive sexual desire disorder. It is the first FDA-approved treatment for this disorder and can improve the number of satisfying sexual events. The drug has been associated with hypotension and syncope.

Ivabradine for systolic heart failure.

Ivabradine works in the sinoatrial node to prolong diastolic depolarization and reduce heart rate. In patients with chronic systolic heart failure, this drug has reduced the risk of hospitalization when used in combination with other optimal pharmacotherapy.

Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin.

Background: Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients. Methods: From March 2010 through March 2013, we collected data prospectively and through medical record reviews of patients with confirmed or suspected botulism who were treated with HBAT under an expanded-access Investigational New Drug program. Results: Among 249 HBAT-treated patients, 1 (<1%) child experienced an HBAT-related serious adverse event (hemodynamic instability characterized by bradycardia, tachycardia, and asystole); 22 (9%) patients experienced 38 nonserious adverse events reported by physicians to be HBAT related. Twelve (5%) deaths occurred; all were determined to be likely unrelated to HBAT. Among 104 (42%) patients with confirmed botulism, those treated early (≤2 days) spent fewer days in the hospital (median, 15 vs 25 days; P < .01) and intensive care (10 vs 17 days; P = .04) than those treated later. Improvements in any botulism sign/symptom were detected a median of 2.4 days and in muscle strength a median of 4.8 days after HBAT. Conclusions: HBAT was safe and provided clinical benefit in treated patients. HBAT administration within 2 days of symptom onset was associated with shorter hospital and intensive care stays. These results highlight the importance of maintaining clinical suspicion for botulism among patients presenting with paralytic illness to facilitate early HBAT treatment before laboratory confirmation might be available. Clinical consultation and, if indicated, HBAT release, are available to clinicians 24/7 through their state health department in conjunction with CDC.

Naloxegol for managing opioid-induced constipation.

Naloxegol is a peripherally acting mu-opioid receptor antagonist for opioid-induced constipation in adults with chronic noncancer pain. This drug's once-daily oral formulation can be used as monotherapy and helps to decrease the constipating effects of opioid therapy; however, it has been associated with abdominal pain.

Role of Bupropion Plus Naltrexone for the Management of Obesity.

Objective. The pharmacology, pharmacokinetics, efficacy, and safety of bupropion plus naltrexone for weight loss were reviewed. Data Sources. A MEDLINE search (1970 to November 2015) was conducted for English-language articles using specific MESH terms. Study Selection and Data Extraction. Published Phase 3 clinical trials with primary endpoints related to weight loss were included and critiqued in this review. Study Selection and Data Extraction. Five trials were retrieved and reviewed regarding the efficacy and safety of bupropion plus naltrexone among obese and overweight patients. Data Synthesis. Bupropion is a dopamine/norepinephrine reuptake inhibitor, and naltrexone is an opioid receptor antagonist. The combination of these agents has led to increased weight loss, compared to placebo, among overweight and obese patients with a body mass index (BMI) at or above 30 or BMI at or above 27 with a comorbid condition. The combination of bupropion and naltrexone can produce an average placebo-subtracted weight loss of 4.25% over 56 weeks. Gastrointestinal (ie, nausea, vomiting, constipation) and central nervous system adverse events (ie, headache, dizziness) were commonly reported, and there was a high dropout rate among participants. Conclusions. Bupropion plus naltrexone has demonstrated effective weight loss, in conjunction with lifestyle modifications, among overweight and obese patients with and without comorbidities. Bupropion plus naltrexone has not been studied among special patient populations, such as those with sleep apnea, osteoarthritis, or extreme BMIs. Additional clinical trials and postmarketing data will provide a better understanding of this medication for weight loss.

Liraglutide: an injectable option for the management of obesity.

OBJECTIVE: To review the efficacy and safety of liraglutide, marketed as Saxenda, a glucagon-like peptide-1 analog for obesity management. DATA SOURCES: A MEDLINE search (1970 to March 2015) was conducted for English-language articles using the terms glucagon-like peptide 1, liraglutide, and obesity. STUDY SELECTION AND DATA EXTRACTION: Published articles pertinent to the efficacy and safety of liraglutide for short- and long-term obesity management among overweight or obese patients and special populations were reviewed and summarized. DATA SYNTHESIS: Based on randomized placebo-controlled and active-comparator studies, liraglutide can increase weight loss among overweight and obese patients in a dose-dependent manner with once-daily doses of 1.2 to 3.0 mg. It has been shown that a higher proportion of patients experienced 5% and 10% weight loss from baseline compared with placebo and orlistat. Data support the potential benefit of liraglutide among overweight and obese patients with prediabetes, as well as women with polycystic ovary syndrome (PCOS) with an inadequate response to metformin. Larger and more robust studies are needed to determine the clinical significance of liraglutide among other agents for obesity in diverse populations. CONCLUSIONS: Liraglutide is an adjunct to lifestyle modifications to improve success rates among overweight or obese individuals without diabetes. It may have a potential role in special populations, such as in those with prediabetes and women with PCOS. Based on its clinical evidence, liraglutide can result in more weight loss from baseline compared with orlistat and placebo. Adverse events associated with liraglutide are primarily gastrointestinal and usually dose dependent.

Inhaled technosphere regular insulin powder.

The lungs are an effective way to deliver insulin for patients with diabetes, but an initial inhaled insulin product was withdrawn from the market because of high cost and inconsistent dosing. This article describes a recently approved inhaled insulin that appears to control blood glucose as well as rapid-acting injectable insulin.

Is combination therapy appropriate for hypothyroidism?

Levothyroxine is the first-line drug for treating hypothyroidism. This article reviews the literature on combination therapy using levothyroxine and liothyronine, and found that only one study produced beneficial outcomes; other studies reported increased adverse reactions among participants. Levothyroxine should remain the drug of choice for hypothyroidism. Adequate trials with homogenous populations and large sample sizes are needed to determine whether combination therapy can be recommended for patients with hypothyroidism.

How can NSAIDs harm cardiovascular and renal function?

Consider the potential cardiovascular and renal effects of nonsteroidal anti-inflammatory drugs when evaluating a patient for short- or long-term use of these drugs. Monitoring and extensive counseling is warranted with this particular class of medications.

Canagliflozin: a new option for managing diabetes.

Canagliflozin is a sodium glucose cotransporter 2 inhibitor for patients with type 2 diabetes and can be given as monotherapy or in combination with other agents, including insulin. Taken orally once daily, canagliflozin can reduce weight and BP, but has been associated with genital mycotic infections.

Exenatide extended-release: a once-weekly option for patients with type 2 diabetes.

Exenatide extended-release is a new long-acting glucagon-like peptide-1 agonist that may be an attractive option for patients desiring to lose weight, who are prone to hypoglycemic episodes, and who have not achieved desired glycemic control with current therapy.

A Possible Case of Gabapentin-Induced Mild Hyperglycemia.

Objective: A possible case of gabapentin-induced mild hyperglycemia is reported. Case Summary: A 63-year-old Caucasian gentleman was treated in a pharmacist-run pharmacotherapy clinic for type 2 diabetes management. His comorbidities included type 2 diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, peripheral vascular disease, Barrett's esophagus, chronic back pain, and obesity. His medications for these comorbidities were continued throughout his care. The patient had no known drug allergies. After 3 months of pharmacist-managed diabetes management, the patient's glucose levels had improved and were within the desired range for a majority of the readings. The patient was consulted to the pain clinic for uncontrolled pain and initiated and titrated on gabapentin from 300 mg per day to 600 to 900 mg 3 times per day. Two weeks later, the patient's glucose levels increased to levels of 150 to 165 mg/dL. The patient's increasing blood glucose values were treated with NPH insulin, which was titrated for several months until he was switched to insulin glargine. Gabapentin was not discontinued since it provided adequate pain control. Discussion: An objective causality assessment revealed that the adverse effect was possible. No other new medications were introduced, current medications were not adjusted, and no alternate causes could be found for increased glucose values. Conclusion: A 63-year-old Caucasian gentleman with type 2 diabetes mellitus developed a possible case of gabapentin-induced mild hyperglycemia after receiving gabapentin for several months with a dose titration. Gabapentin could be considered as a cause for otherwise unexplained hyperglycemia in a patient.

[89Zr]-CD8 ImmunoPET imaging of glioblastoma multiforme response to combination oncolytic viral and checkpoint inhibitor immunotherapy reveals CD8 infiltration differential changes in preclinical models.

Rationale: Novel immune-activating therapeutics for the treatment of glioblastoma multiforme (GBM) have shown potential for tumor regression and increased survival over standard therapies. However, immunotherapy efficacy remains inconsistent with response assessment being complicated by early treatment-induced apparent radiological tumor progression and slow downstream effects. This inability to determine early immunotherapeutic benefit results in a drastically decreased window for alternative, and potentially more effective, treatment options. The objective of this study is to evaluate the effects of combination immunotherapy on early CD8+ cell infiltration and its association with long term response in orthotopic syngeneic glioblastoma models. Methods: Luciferase positive GBM orthotopic mouse models (GSC005-luc) were imaged via [89Zr]-CD8 positron emission tomography (PET) one week following treatment with saline, anti-PD1, M002 oncolytic herpes simplex virus (oHSV) or combination immunotherapy. Subsequently, brains were excised, imaged via [89Zr]-CD8 ImmunoPET and evaluated though autoradiography and histology for H&E and CD8 immunohistochemistry. Longitudinal immunotherapeutic effects were evaluated through [89Zr]-CD8 PET imaging one- and three-weeks following treatment, with changes in tumor volume monitored on a three-day basis via bioluminescence imaging (BLI). Response classification was then performed based on long-term BLI signal changes. Statistical analysis was performed between groups using one-way ANOVA and two-sided unpaired T-test, with p < 0.05 considered significant. Correlations between imaging and biological validation were assessed via Pearson's correlation test. Results: [89Zr]-CD8 PET standardized uptake value (SUV) quantification was correlated with ex vivo SUV quantification (r = 0.61, p < 0.01), autoradiography (r = 0.46, p < 0.01), and IHC tumor CD8+ cell density (r = 0.55, p < 0.01). Classification of therapeutic responders, via bioluminescence signal, revealed a more homogeneous CD8+ immune cell distribution in responders (p < 0.05) one-week following immunotherapy. Conclusions: Assessment of early CD8+ cell infiltration and distribution in the tumor microenvironment provides potential imaging metrics for the characterization of oHSV and checkpoint blockade immunotherapy response in GBM. The combination therapies showed enhanced efficacy compared to single agent immunotherapies. Further development of immune-focused imaging methods can provide clinically relevant metrics associated with immune cell localization that can inform immunotherapeutic efficacy and subsequent treatment response in GBM patients.

Development of Quality Measures for Inpatient Diabetes Care and Education Specialists: A Call to Action.

ABSTRACT: Diabetes and hyperglycemia are associated with an increased risk of in-hospital complications that lead to longer lengths of stay, increased morbidity, higher mortality, and risk of readmission. Diabetes care and education specialists (DCESs) working in hospital settings are uniquely prepared and credentialed to serve as content experts to facilitate change and implement processes and programs to improve glycemic-related outcomes. A recent survey of DCESs explored the topic of productivity and clinical metrics. Outcomes highlighted the need to better evaluate the impact and value of inpatient DCESs, advocate for the role, and to expand diabetes care and education teams to optimize outcomes. The purpose of this article was to recommend strategies and metrics that can be used to quantify the work of inpatient DCESs and describe how such metrics can help to show the value of the inpatient DCES and assist in making a business case for the role.

Significant publications in diabetes pharmacotherapy and technology in 2020.

INTRODUCTION: The most significant articles on diabetes pharmacotherapy and technology in the peer-reviewed literature from 2020, as determined by a panel of pharmacists with expertise in diabetes care and education, are summarized. AREAS COVERED: Members of the Association of Diabetes Care and Education Specialists Pharmacy Community of Interest were selected to review articles published in prominent peer-reviewed journals in 2020 that most impacted diabetes pharmacotherapy and technology. A list of 37 nominated articles were compiled (22 in diabetes pharmacotherapy and 15 in diabetes technology). Based on discussion among the authors, the articles were ranked based on significant contribution, impact, and diversity to diabetes pharmacotherapy and technology. The top 10 highest ranked publications (n = 6 for diabetes pharmacotherapy and n = 4 in diabetes technology) are summarized in this article. EXPERT OPINION: With the significant number of publications in diabetes care and education, it can be challenging and overwhelming to remain current with published literature. This review article may be helpful in identifying key articles in diabetes pharmacotherapy and technology from the year 2020.