Tirzepatide: A Novel Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide 1 Receptor Agonist for the Treatment of Type 2 Diabetes: The First Twincretin.

Tirzepatide is a dual-action glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 (GLP-1) receptor agonist and the first drug in a new class known as twincretins. It is similar to GLP-1 receptor agonists but provides a synergistic enhancement of the incretin effect to control blood glucose levels and reduce weight. Across the SURPASS research program trials, tirzepatide lowered A1C by 1.7-2.4% from baseline. The proportion of patients using tirzepatide who achieved an A1C <7% ranged from 91 to 97%. Patients in the treatment groups averaged a weight loss of 5.44-11.34 kg (12-25 lb). Across all trials, patients on tirzepatide 15 mg lost 8.8-12.9 kg (19.4-28.44 lb) or 9.17-13.7% body weight. In the SURMOUNT-1 trial, maximum weight loss was 23.6 kg (52 lb) or 22.5% body weight. Tirzepatide is a potent new weapon in the arsenal against diabetes.

The First Interchangeable Biosimilar Insulin: Insulin Glargine-yfgn.

On March 23, 2020, all insulin products were reclassified as biologics instead of drugs under the Biological Price Competition and Innovation (BPCI) Act of 2009. This allows biosimilar insulin products to be manufactured when the patent expires for the reference biologic, sometimes called the originator or brand name product. A biosimilar product may not be substituted for the reference biologic at the pharmacy counter unless the biosimilar undergoes further switch trials to earn the designation as an interchangeable biosimilar. Insulin glargine-yfgn 100 units/mL is the first biosimilar insulin to attain interchangeable status with the reference insulin glargine. In the INSTRIDE 1 and INSTRIDE 2 trials, insulin glargine-yfgn has proven noninferiority regarding blood glucose reduction and adverse effect profile versus reference insulin glargine; even in the INSTRIDE 3 trial in which treatment of diabetes was switched between insulin glargine-yfgn and reference insulin glargine throughout the trial without statistically significant changes to glucose levels or adverse effects. Insulin glargine-yfgn may be substituted at the pharmacy counter without consultation with the prescriber, in accordance with state laws. In suit with other biosimilars, insulin glargine-yfgn's list price is significantly lower than other insulin glargine products. This increases market competition leading to decreases in costs of other insulin glargine products. Many patients who could not previously afford insulin therapy may now have significantly improved access to treatment. Providers will need education to increase awareness of these new biosimilars and interchangeable biosimilar insulin products, cost benefits, and substitution allowances.

Leveraging Social Media and Web Presence to Discuss and Promote Diversity, Equity, and Inclusion in Radiology.

PURPOSE: This article seeks to better understand how radiology residency programs leverage their social media presences during the 2020 National Residency Match Program (NRMP) application cycle to engage with students and promote diversity, equity, and inclusion to prospective residency applicants. METHODS: We used publicly available information to determine how broad a presence radiology programs have across specific platforms (Twitter [Twitter, Inc, San Francisco, California], Facebook [Facebook, Inc, Menlo Park, California], Instagram [Facebook, Inc], and website pages) as well as what strategies these programs use to promote diversity, equity, and inclusion. RESULTS: During the 2020 NRMP application cycle, radiology residency programs substantially increased their social media presence across the platforms we examined. We determined that 29.3% (39 of 133), 58.9% (43 of 73), and 29.55% (13 of 44) of programs used Twitter, Instagram, and Facebook, respectively; these accounts were established after an April 1, 2020, advisory statement from the NRMP. Program size and university affiliation were correlated with the degree of social media presence. Those programs using social media to promote diversity, equity, and inclusion used a broad but similar approach across programs and platforms. CONCLUSION: The events of 2020 expedited the growth of social media among radiology residency programs, which subsequently ushered in a new medium for conversations about representation in medicine. However, the effectiveness of this medium to promote meaningful expansion of diversity, equity, and inclusion in the field of radiology remains to be seen.

An exploratory survey on the awareness and usage of clinical practice guidelines among clinical pharmacists.

Background: The NHLBI has not developed clinical practice guidelines since 2007. As a result, multiple organizations have released competing guidelines. This has created confusion and debate among clinicians as to which recommendations are most applicable for practice. Objectives: To explore preliminary attitudes, awareness, and usage of clinical practice guidelines in practice and teaching for hypertension, dyslipidemia and asthma among clinical pharmacists. Methods: Clinical pharmacists across the US were surveyed electronically over a two week period in Spring 2019 regarding utilization and knowledge of practice guidelines for hypertension, dyslipidemia, and asthma. Clinical cases were included to evaluate application of guidelines. Descriptive statistics, Chi-square analysis, and Wilcoxon signed-rank test were conducted. Statistical significance level was set to 0.01 to account for multiple tests conducted on the same survey participants. Results: Forty-eight, 34, and 28 pharmacists voluntarily completed hypertension, dyslipidemia, and asthma survey questions, respectively. Interactions by disease state (p < 0.001) revealed more pharmacists (93%) reporting to have ≤50% patient load in managing asthma and more pharmacists (95%) had read the full summary/report of the most recent hypertension guideline. Primary reasons why the most recent guideline was not selected were also significantly different by disease state (interaction; p < 0.001). For dyslipidemia and asthma, pharmacists had a higher mean rating of agreement (p < 0.007) in having the most confidence in the most recent as compared to older guidelines. Proportionally more clinical cases were answered correctly (interaction; p < 0.001) when pharmacists applied the most recent guideline for hypertension (84%), while the opposite outcome was found for asthma (27%). Conclusion: While more pharmacists selected the most recent guideline for practice and teaching, there was inconsistent application of guidelines to clinical cases. Further studies with a larger representation of pharmacists are warranted to more definitively determine factors influencing guideline preference and usage.

The role of basal insulin and GLP-1 receptor agonist combination products in the management of type 2 diabetes.

The prevalence of type 2 diabetes necessitates the development of new treatment options to individualize therapy. Basal insulin has been a standard treatment option for years, while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have grown in use over the past decade due to glucose-lowering efficacy and weight loss potential. There are two new combination injectable products that have recently been approved combining basal insulins with GLP-1 RAs in single pen-injector devices. United States guidelines recently emphasize the option to use combination injectable therapy with GLP-1 RAs and basal insulin once the basal insulin has been optimally titrated as a second- or third-line agent in addition to metformin without reaching the goal A1c. Insulin glargine/lixisenatide 100/33 (IGlarLixi) can be dosed between 15 and 60 units once daily from a single pen-injector device. Insulin degludec/liraglutide 100/3.6 (IDegLira) can be dosed between 10 and 50 units once daily, also from a single pen-injector device. Maximum doses, while measured in units, correspond to limits defined by each individual GLP-1 RA. The dual use of basal insulin plus GLP-1 RA is non-inferior compared with basal insulin plus a single injection of prandial insulin at the largest meal and compared with twice daily-dosed premixed insulins; and this combination is associated with weight loss and less hypoglycemia. These new combination products could help providers effectively and efficiently follow clinical practice guidelines while enhancing patient adherence with injectable medications.

Pharmacist-managed short-acting beta agonist refill service in a general pediatric clinic.

OBJECTIVES: To use a pharmacist-managed short-acting beta agonist (SABA) service (1) to determine the patient's rationale for SABA refill requests, (2) to assess adherence to current controller therapy and current level of disease control, and (3) to characterize the pharmacist's recommendations made in response to a patient's SABA refill request. SETTING: An academic-based general pediatric clinic. PRACTICE DESCRIPTION: SABA overuse is a marker of increased morbidity and mortality in children with asthma. This article describes a pharmacist-managed SABA refill telephone service. PRACTICE INNOVATION: The pediatric ambulatory care pharmacy team assessed and authorized (or denied) all SABA refill requests, provided education, and facilitated appropriate follow-up using a telephone service. INTERVENTIONS: Upon receiving a patient-requested SABA refill, the pharmacist identified the reason for the SABA request, assessed asthma control, and determined adherence to daily controllers or spacer use, if applicable. Education was also provided. Data obtained were used to determine SABA refill approval. EVALUATION: Primary reasons for SABA refill request were for (1) current symptom management and (2) no refills remaining in the absence of symptoms. Forty-two (50%) SABA refill requests were eligible for refill per the clinic algorithm, yet 70% actually received a refill after assessment by the pharmacist. Asthma control was assessed as 26% well controlled, 38% not well controlled, and 36% very poorly controlled. Forty-eight percent of patients prescribed daily controller medications were deemed adherent. Spacers were used in 43 of 76 (56%) patients using metered dose inhalers. Education was provided to 82% of caregivers. Pharmacists facilitated asthma follow-up visits in 41 of 84 (49%) patients contacted, and 61% of those appointments were kept. CONCLUSIONS: Pharmacist management of a SABA refill telephone service provides an additional means for delivery of asthma education, facilitates follow-up asthma care, helps to identify patients at risk for increased morbidity and mortality due to the overuse of SABAs, and provides another mechanism for medication refills.

Barriers to Patient Use of Control Solution for Glucose Meters: Surveys of Patients, Pharmacists, and Providers in a Metropolitan Area.

BACKGROUND: An important factor in controlling diabetes is self-monitoring of blood glucose. Manufacturers of glucose meters recommend routine use of control solution to ensure accuracy. Previous studies have demonstrated that glucose meters vary in accuracy and that patients are not using control solution as recommended. The purpose of this study is to identify potential barriers to control solution use from multiple perspectives including patient, pharmacist, and provider. METHODS: This study was a prospective, observational survey design. First, 25 randomly selected chain and independent pharmacies in the Tulsa metropolitan area were audited for control solution accessibility. These pharmacies were then used to survey pharmacists, via telephone, regarding control solution inventory and perception of importance of use. Next, providers were electronically surveyed on their routine practice recommendations, while 60 patients with diabetes were randomly selected for telephone survey on use and perceptions of control solution. RESULTS: Twenty-five pharmacies were audited and 23 pharmacists, 60 patients, and 29 providers were surveyed. Only 39% of pharmacies stated they supplied control solution, however, only 1 pharmacy visibly stocked it. The only patient factor that appeared to have an impact on control solution usage was having type 1 versus type 2 diabetes (38% vs 15%). Providers are aware of what control solution is (62%), but only half felt it should be routine practice with 44% of those never recommending it. CONCLUSION: This study raises awareness for the need to educate patients, providers, and pharmacists about use of control solution to ensure glucose meter accuracy.

A literacy-sensitive approach to improving antibiotic understanding in a community-based setting.

OBJECTIVE: Antibiotic misuse contributes to antibiotic-resistant bacterial infections. Patient and prescriber knowledge and behaviors influence antibiotic use. Past research has focused on describing and influencing prescriber behavior with less attention to the patient role in antibiotic use. This study seeks to: (1) develop and deploy a program to enhance patient knowledge about antibiotic use; (2) evaluate whether providing patient education is associated with improvements in antibiotic knowledge in a community-based sample; and (3) explore whether health literacy may be associated with knowledge of appropriate antibiotic use. METHOD: This study developed, deployed, and evaluated whether community-based educational seminars enhance patient knowledge about antibiotic use. KEY FINDINGS: Twenty-eight participants from five locations completed the seminar. The antibiotic knowledge index score significantly increased by 2.0 points on the 14 point knowledge index from 10.95 (±2.88) to 12.95 (±1.72) (P = 0.0011) for the 19 participants completing both the pre and post-test. CONCLUSION: A community-based educational seminar on appropriate antibiotic use can effectively increase patient understanding of their role in antibiotic stewardship and combat the inappropriate use of antibiotics.

Interventions to improve dissemination and implementation of Hepatitis B vaccination in patients with diabetes.

OBJECTIVE: The purpose of this study was to assess provider awareness of routine vaccinations recommended for patients with diabetes and to determine whether pharmacist-led interventions are associated with increased provider implementation of recommendations for hepatitis B vaccination. METHODS: This study was conducted in 3 phases at 2 outpatient clinics affiliated with an academic institution. In phase 1, adults with diabetes who visited the clinics between January and November 2012 and who were eligible for the hepatitis B vaccine were identified. In phase 2, medical residents were surveyed twice for vaccine recommendations and reasons for (not) recommending the hepatitis B vaccine, specifically. Residents were then provided a pharmacist-led in-service about hepatitis B vaccine recommendations. The third phase was initiated in April 2013, following postintervention observation from December 2012 through March 2013. RESULTS: Forty-eight of 100 (48%) medical residents attended the in-service and completed both surveys, with 77% indicating they did not recommend the hepatitis B vaccine. During phase 1, 1441 patients were identified, 0.6% (n = 8) of whom had received at least the first dose of the series. In phase 3, 946 patients were identified with 1.7% (n = 16) having received at least the first dose (P = 0.007). CONCLUSION: An attempt to disseminate updated recommendations to providers via educational in-service was successful in increasing the percentage of eligible patients vaccinated with the hepatitis B vaccine.

Novel Concentrated Insulin Delivery Devices: Developments for Safe and Simple Dose Conversions.

To aid the burden of large dosing volumes, concentrated insulin products have been available in some form since the 1950s, albeit requiring significant and cumbersome detail in prescribing, converting doses from other products, and educating patients on how to administer. In 2015 and 2016, new concentrated products have been introduced that are available exclusively in pen devices that perform the conversion automatically, and thus, help to bypass the necessity for confusing calculations or administration. Providers and patients accustomed to traditional methods must recognize the differences and utility of these products to avoid dosing errors, as there are major differences in dosing procedures as well as their role in clinical practice. For example, the novel concentrated insulins (aside from U-500 products) are not solely indicated for severe insulin resistance. Use of novel agents may decrease the number of injections required, decrease complexity for patients and providers, reduce errors, and avoid conversion calculations. It is imperative that clinicians appreciate the nuances among the agents to choose an insulin product that is appropriate and fits a patient's needs and preferences.

Identifying opportunities to improve medication management in transitions of care.

PURPOSE: The types and causes of medication discrepancies during the transition from inpatient to ambulatory care were investigated. METHODS: A descriptive study was conducted at an academic outpatient group practice affiliated with a private nonacademic hospital to (1) describe discrepancies between inpatient discharge summaries and patient-reported medication lists, (2) identify patient and system factors related to breakdowns in medication documentation, and (3) determine reasons for medication discrepancies. During a four-month period, 17 patients at high risk for medication misadventures while transitioning from hospital care to outpatient follow-up were contacted by telephone soon after discharge and asked to provide information on all medications they were taking. Patient-reported medication lists were compared with the corresponding discharge summaries, and medication discrepancies were categorized by patient- and system-level factors using a validated instrument. RESULTS: Of the total of 96 discrepancies identified, more than two thirds (n = 67, 68%) involved the omission of a prescribed medication from either the patient-reported list or the discharge summary. Cardiovascular medications, including antihypertensives, antilipemics, diuretics, and antiarrhythmics, accounted for almost one quarter of all medication discrepancies. About 15% (n = 14) and 16% (n = 15) of identified discrepancies related to medication dose and frequency, respectively. CONCLUSION: Among 17 patients transitioning from inpatient to outpatient care, nearly 100 discrepancies between patient-reported medication lists and discharge summaries were identified. Most discrepancies were attributed to nonintentional nonadherence and resumption of home medications without instructions to do so. All 17 patients had at least 1 medication discrepancy categorized as involving a system-level factor.

Pharmacist-led educational and error notification interventions on prescribing errors in family medicine clinic.

OBJECTIVES: To determine the rate of prescribing errors in a family medicine clinic and the subsequent impact of pharmacist-led educational and error notification interventions on prescribing errors. DESIGN: Single site, pre-post study design. SETTING: An outpatient academic family medicine clinic serving pediatric and adult populations in Oklahoma from March 1, 2011, through April 30, 2012. PARTICIPANTS: 24 resident physicians who prescribed medications during routine outpatient visits. INTERVENTION: A prescribing educational program, audit and feedback methods, and weekly newsletter. MAIN OUTCOMES MEASURE: Percentage of prescription errors and physician error rate before and after intervention among pediatric and adult populations. RESULTS: During the two assessment periods, 24 resident physicians wrote 2,753 prescriptions for 394 pediatric and 899 adult patients. The overall percentage of prescription errors decreased from 18.6% during March 2011 to 14.5% during April 2012 (P = 0.004). Errors were more commonly seen with prescriptions written for pediatric patients (24.9%) than for adult patients (13.9%) (P = 0.001). Individual physician error rates ranged from 5% to 36% (mean ± SD 16.5% ± 8.1). Physicians committed significantly fewer prescribing errors during the postintervention assessment period (14.9%) than during the preintervention assessment period (20.9%) (P = 0.002). Controlling for time, pediatric prescription error rates among physicians who participated in the educational intervention were 36% lower than the error rates among physicians who did not participate (rate ratio 0.64 [95% CI 0.45, 0.91], P = 0.01). CONCLUSION: The pharmacist-led educational program was effective in reducing pediatric prescribing errors among resident physicians in a family medicine clinic.

Influence of the type of Basal insulin and other variables on clinical outcomes in children with newly diagnosed type 1 diabetes.

Background. Basal insulin detemir and glargine each have characteristics that may make them a superior choice in children and adolescents with type 1 diabetes, but there is a paucity of data on glycemic results in this population. Objective. Examination of variables associated with achievement of HbA1c goal in children and adolescents with newly diagnosed type 1 diabetes. Methods. The primary outcome, factors associated with achievement of HbA1c goal, was examined in a retrospective chart review. Variables, including type of basal insulin, were collected during the first year of diagnosis of patients in a pediatric diabetes clinic. Secondary outcomes included change in HbA1c, severe hypoglycemic events, and episodes of DKA. Results. 94 patients were included in the study. HbA1c at diagnosis was found to be a significant predictor of achievement of goal at 3 months (P = 0.002) and of change in HbA1c at 3 and 12 months (P < 0.001 for each). Severe hypoglycemia and episodes of DKA were uncommon. Conclusions. Choice of basal insulin was not found to be a predictor of achieving HbA1c goal or of change in HbA1c over the course of the first year of diagnosis with type 1 diabetes.

Management of a prediabetes case with the DPP-4 inhibitor sitagliptin.

OBJECTIVE: It is important to prevent or slow the progression of prediabetes to type 2 diabetes and, therefore, reduce the risk of long-term complications. New therapeutic options will allow more patients to be effectively managed. Although theorized to be effective for prediabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors have not been studied in this population. The purpose of this article is to report the results of a case in which a patient with prediabetes was treated with the DPP-4 inhibitor, sitagliptin. CASE SUMMARY: A 56-year-old woman was diagnosed with prediabetes at a hemoglobin A1C (A1C) of 6.2%. After 6 months of consistent lifestyle modifications, her A1C was 6.3%, and she wanted to start a medication to prevent disease progression. Because of anticipated risk or intolerability with standard prediabetes treatments, she was started on sitagliptin 100 mg daily; 6 weeks later, she noted improvements in glucometer readings. After 18 months on sitagliptin, her A1C had improved to 5.8% without further lifestyle improvements, and by 32 months, her A1C had improved to 5.6%. Her A1C was maintained within or below the prediabetes range of 5.7% to 6.4% over 3 years of treatment with sitagliptin. DISCUSSION: Although human studies with DPP-4 inhibitors are lacking, the available studies have shown improvements in ß-cell function and postprandial and fasting glucose levels. Furthermore, animal studies have shown a delay in progression of prediabetes. No case reports have been found regarding DPP-4 inhibitor use in prediabetes. CONCLUSION: Sitagliptin may have a role in treating prediabetes and should be further studied.

Cardiovascular disease and non-steroidal anti-inflammatory drug prescribing in the midst of evolving guidelines.

RATIONALE, AIMS AND OBJECTIVES: Responding to safety concerns, the American Heart Association (AHA) published guidelines for non-steroidal anti-inflammatory drug (NSAID) use in patients with pre-existing cardiovascular disease (CVD) during 2005 and revised them in 2007. In the revision, a stepped approach to pain management recommended non-selective NSAIDs over highly selective NSAIDs. This research evaluated NSAID prescribing during and after guideline dissemination. METHOD: A cross-sectional sample of 8666 adult, community-based practice visits with one NSAID prescription representing approximately 305 million visits from the National Ambulatory Medical Care Survey (NAMCS) from 2005 to 2010 was studied. Multivariable logistic regression controlling for patient, provider and visit characteristics assessed the associations between diagnosis of CVD and NSAID type prescribed during each calendar year. Visits were stratified by arthritis diagnosis to model short-term/intermittent and long-term NSAID use. RESULTS: Approximately one-third (36.8%) of visits involving a NSAID prescription included at least one of four diagnoses for CVD (i.e. hypertension, congestive heart failure, ischaemic heart disease or cerebrovascular disease). Visits involving a CVD diagnosis had increased odds of a prescription for celecoxib, a highly selective NSAIDs, overall [adjusted odds ratio (AOR) = 1.29, 95% confidence interval (CI): 1.06-1.57] and in the subgroup of visits without an arthritis diagnosis (AOR = 1.45, 95% CI: 1.11-1.89). Results were not statistically significant for visits with an arthritis diagnosis (AOR = 1.10, 95% CI: 0.47-2.57). When analysed by year, the relationship was statistically significant in 2005 and 2006, but not statistically significant in each subsequent year. CONCLUSION: National prescribing trends suggest partial implementation of AHA guidelines for NSAID prescribing in CVD from 2005 to 2010.

Perirhinal cortex represents nonspatial, but not spatial, information in rats foraging in the presence of objects: comparison with lateral entorhinal cortex.

The medial temporal lobe (MTL) is involved in mnemonic processing. The perirhinal cortex (PRC) plays a role in object recognition memory, while the hippocampus is required for certain forms of spatial memory and episodic memory. The lateral entorhinal cortex (LEC) receives direct projections from PRC and is one of the two major cortical inputs to the hippocampus. The transformations that occur between PRC and LEC neural representations are not well understood. Here, we show that PRC and LEC had similarly high proportions of neurons with object-related activity (PRC 52/94; LEC 72/153), as expected from their locations in the "what" pathway into the hippocampus. However, LEC unit activity showed more spatial stability than PRC unit activity. A minority of LEC neurons showed stable spatial firing fields away from objects; these firing fields strongly resembled hippocampal place fields. None of the PRC neurons showed this place-like firing. None of the PRC or LEC neurons demonstrated the high firing rates associated with interneurons in hippocampus or medial entorhinal cortex, further dissociating this information processing stream from the path-integration based, movement-related processing of the medial entorhinal cortex and hippocampus. These results provide evidence for nonspatial information processing in the PRC-LEC pathway, as well as showing a functional dissociation between PRC and LEC, with more purely nonspatial representations in PRC and combined spatial-nonspatial representations in LEC.

Integration of team-based learning strategies into a cardiovascular module.

OBJECTIVES: To integrate components of team-based learning (TBL) into a cardiovascular module to increase students' responsibility for their own learning and actively engage students across 2 campuses in patient cases. DESIGN: An existing cardiovascular course module was modified by replacing 8 hours of lectures with self-directed learning (SDL) assignments and transforming case discussion sessions using TBL methodologies. Case discussions were delivered using TBL methods to increase engagement of all students across both campuses while maintaining a low faculty-to-student ratio in the classrooms. Readiness assurance quizzes were performed with each SDL assignment and TBL case session. ASSESSMENT: Student and faculty satisfaction improved with the addition of SDL assignments and TBL cases without adverse effects on grades in the wake of the 14% decrease in lecture time. Total faculty time required increased primarily in the first year because of development of course materials. CONCLUSION: A modified TBL format was successfully integrated into a lecture-based cardiovascular module, resulting in improved student and faculty satisfaction with the course and no adverse effect on student performance.