A Review of the Safety and Efficacy of Bexagliflozin for the Management of Type 2 Diabetes.

OBJECTIVE: To review the pharmacology of bexagliflozin in addition to its safety and efficacy from available clinical trials used for its approval, as well as available clinical evidence to date. DATA SOURCES: A search of the National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov) and PubMed database was performed from inception through June 1, 2023. STUDY SELECTION AND DATA EXTRACTION QUANTIFICATION: The following study designs were included: meta-analyses, systematic review, clinical trial, or observational study design. Abstracts and drug monographs were also reviewed. Narrative or scoping reviews were excluded. Only articles in the English language and those evaluating the pharmacology, pharmacokinetics, safety, or efficacy of bexaglifozin in humans were included. DATA SYNTHESIS: Bexagliflozin reduces hemoglobin A1c ~0.5% with similar reductions in systolic blood pressure and body weight to other SGLT2 inhibitors. No cardiovascular outcomes trial is published, nor ongoing at this time. Adverse effects are similar to other SGLT2 inhibitors (genital mycotic and urinary tract infections, increased urination) including a warning for lower extremity amputation similar to canagliflozin. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Although no cost-effectiveness data are available, statements from the manufacturer suggest a competitive price point. Given limited trial data, lower cost, if chosen, may create a temporary niche for bexagliflozin pending generic availability of other SGLT2 inhibitors. However, given lack of cardiovascular and renal outcome data, empagliflozin, dapagliflozin, or canagliflozin may be preferred. CONCLUSION: Bexagliflozin appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2D.

Implementation of a pharmacy residency wellness program: Impact on burnout and mindfulness and lessons learned.

BACKGROUND AND PURPOSE: Attention to wellness in the pharmacy workplace is occurring. To maintain accreditation, pharmacy residency programs must incorporate wellness and resilience initiatives. EDUCATIONAL ACTIVITY AND SETTING: Orlando Health created a pharmacy residency wellness program for post-graduate year one (PGY-1) and post-graduate year two (PGY-2) pharmacy residents to address wellness and burnout. The wellness program included assignment of a mentor, development of a personal wellness plan, completion of monthly reflections, and wellness and resiliency training. FINDINGS: Pharmacy residents anonymously completed the Oldenburg Burnout Inventory (OLBI) and Mindful Attention Awareness Scale (MAAS) at the beginning and end of the residency year. A total of nine pharmacy residents were eligible to participate in the wellness program. Eight residents completed the pre-survey, and seven residents completed the post-survey. No change was observed in the overall median OLBI score (pre-program = 35 [IQR 31.5-37.3] and post-program = 36 [IQR 31-37.5]; P = .683). Similar results were found on the OLBI for disengagement and exhaustion, correlating with low burnout risk. There was no change in the overall median MAAS score (pre-program = 3.7 [IQR 3.6-4.1] and post-program = 3.8 [IQR 3.5-3.9]; P = 1.000). Overall, feedback from the pharmacy residents after program completion was positive. SUMMARY: Pharmacy residents participating in the wellness program at our institution had low risk for burnout and a high level of mindfulness pre- and post-program completion. Pharmacy residents enjoyed participating in the wellness program and found the program to be valuable, supporting its continued implementation.

Pharmacist-driven continuous glucose monitoring in community and ambulatory care pharmacy practice: A scoping review.

BACKGROUND: Continuous glucose monitoring (CGM) devices improve clinical outcomes and facilitate achieving patient-specific goals. However, opportunities and barriers to implementation of pharmacist-driven CGM services are not well-described. OBJECTIVES: This scoping review was conducted to identify opportunities and barriers to implementing pharmacist-driven CGM services in the community and ambulatory care setting. Clinical outcomes resulting from pharmacist-driven CGM were also explored. METHODS: A health librarian searched Ovid MEDLINE, Cochrane CENTRAL, Embase, Web of Science, Scopus, International Pharmaceutical Abstracts using keywords and subject headings from inception through December 2, 2022 to identify studies describing pharmacist or pharmacy-based CGM programs. No publication type, date limits, language restrictions, or other filters were applied. The database search was supplemented by a search of Google Scholar and a citation search of preselected gold standard articles. RESULTS: The scoping review initially identified 942 citations of which 249 passed abstract screening and 11 were included in the review. Among studies, the most common design was retrospective, populations varied, control groups were not consistently used, follow-up was primarily short, and sample sizes were small. One study evaluated pharmacist-driven CGM in a community pharmacy setting. Ten studies took place in the ambulatory care setting. Barriers to initiating pharmacist-driven CGM as a clinical service include educational, logistical, workflow, and financial incentive. Beneficial outcomes from pharmacist-driven CGM include improved quality of life, increased empowerment, and improved glycemic control. CONCLUSION: There is lack of strong evidence to support pharmacist-driven CGM in the community pharmacy setting. However, small studies suggest pharmacist-driven CGM is feasible and beneficial in the ambulatory care setting. Further exploration of how educational, logistical, workflow, and financial barriers can be overcome is warranted, given potential for improved clinical outcomes.

Inclisiran for the Treatment of Hyperlipidemia and for Atherosclerotic Cardiovascular Disease Risk Reduction: A Narrative Review.

PURPOSE: Inclisiran is a novel nonstatin therapy providing significant reduction in low-density lipoprotein cholesterol (LDL-C) as well as improvements in other lipid biomarkers. This review summarizes data from postapproval publications regarding the impact of inclisiran on lipids and cardiovascular risk reduction, as well as its tolerability and cost-effectiveness. METHODS: A search of PubMed for inclisiran was used to identify articles published since its approval by the US Food and Drug Administration (FDA). Clinical research studies reporting meta-analysis; pooled patient-level trial analyses; cost-effectiveness analyses; new human data; prespecified, post-hoc, or subgroup trial analyses; and clinical trial extensions were included. FINDINGS: The search identified 153 citations; 16 studies were included. FDA-approval trials, subsequent pooled patient-level trial analyses, and extension studies found that inclisiran, administered with and without maximally tolerated statin therapy, reduced LDL-C by ≈50%, with the reduction sustained for 4 years. Inclisiran appeared to be well tolerated, even long-term, with injection-site reactions being the most common adverse effect. A patient-level pooled analysis of data from Phase III trials suggested that cardiovascular events were reduced with inclisiran versus placebo (7.1% vs 9.4%; odds ratio = 0.74 [95% CI, 0.58-0.94]). Inclisiran is suggested to be cost-effective based the presumed cardiovascular benefit commensurate with LDL-C reduction. IMPLICATIONS: The cardiovascular benefit and cost-effectiveness of inclisiran are promising, though not definitive. The results of a large-scale study of the effects of inclisiran on cardiovascular outcomes are expected in 2026; until then, the nonstatin therapies primarily prescribed for LDL-C reduction remain proprotein convertase subtilisin/kexin (PCSK)-9 inhibitors and ezetimibe. However, inclisiran is a reasonable alternative to, PCSK-9 inhibitors, in patients who struggle with the self-injection of or adherence to PCSK-9 inhibitors as inclisiran maintenance therapy is administered twice yearly by a health care professional.

Impact of Overbasalization on Clinical Outcomes in Patients With Type 2 Diabetes: A Post Hoc Analysis of a Large Randomized Controlled Trial.

The American Diabetes Association's Standards of Medical Care in Diabetes emphasize the need for awareness regarding overbasalization (basal insulin doses >0.5 units/kg/day without bolus insulin) in the treatment of type 2 diabetes. However, outcomes data on the impact of overbasalization are limited. This post hoc analysis of a large randomized controlled trial suggests that an insulin therapy regimen involving overbasalization compared with a basal-bolus insulin regimen that avoids overbasalization is less effective at lowering A1C and may be associated with increased cardiovascular risk. Clinicians should consider alternative approaches to glycemic control before increasing basal insulin doses to >0.5 units/kg/day.

Effect of Antidepressants on Glucagon-Like Peptide-1 Receptor Agonist-Related Weight Loss.

Background: Depression and obesity have a bidirectional relationship making the management of one, without the other, problematic. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a preferred medication class for diabetes and obesity treatment given their weight loss effect; however, it is not known how antidepressants impact this effect. Objective: To assess the impact of antidepressant use on GLP-1 RA-associated weight loss in patients with or without type 2 diabetes mellitus. Methods: This was a retrospective, propensity matched, cohort study conducted using TriNetX. The study identified patients initiating a GLP-1 RA being treated with citalopram/escitalopram, bupropion, or no antidepressant. Cohorts were propensity score matched to analyze the primary outcome of mean end-of-study (77-371 days) body weight. Results: An initial query identified 31 273 patients eligible for analysis (30 160 receiving no antidepressant, 311 receiving bupropion, and 802 receiving citalopram/escitalopram). After propensity score matching, the study found patients receiving citalopram/escitalopram were taking more antidiabetic therapies at baseline compared with patients not treated with an antidepressant. Patients in the antidepressant cohorts experienced less weight loss compared with their respective matched cohorts not receiving antidepressants (citalopram/escitalopram -0.73 kg versus -1.74 kg; bupropion -0.84 kg versus -3.46 kg). Only the bupropion cohort was significantly heavier at end-of-study versus the non-antidepressant cohort (108 kg versus 103 kg, P = 0.018). Conclusion and Relevance: Antidepressants may diminish the weight loss effect of GLP-1 RAs. Additional research is needed to assess whether all GLP-1 RAs are affected similarly and the optimal weight loss strategies in patients receiving antidiabetic therapy with comorbid depression.

Pharmacist-Physician Collaborative Practice to Improve Diabetes Care at Tampa General Medical Group.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a pharmacist-physician collaborative effort to reduce A1C and blood pressure and thereby lower risks for complications for people with diabetes being treated at a network of family care clinics in the Tampa, FL, area.

Flash Continuous Glucose Monitoring: A Practical Guide and Call to Action for Pharmacists.

Despite advances in diabetes technology, the proportion of patients with type 2 diabetes achieving recommended glycemic goals remains suboptimal. There is a growing interest in flash continuous glucose monitoring (CGM) among patients, pharmacists and providers. Pharmacists are well positioned to collaborate with patients and providers in ambulatory care or community-based settings to allow a greater number of patients with diabetes to harness the benefits of flash CGM. The purpose of this narrative review is to provide pharmacists with a background on flash CGM technology, review the data supporting pharmacist-driven flash CGM services, and address common questions that arise in pharmacy practice surrounding flash CGM.

Measurement of Pharmacist-Physician Collaborative Care on Therapeutic Inertia in Patients With Type 2 Diabetes.

BACKGROUND: Team-based care practice models have been shown to improve diabetes-related therapeutic inertia, yet the method and type of antidiabetic treatment intensification (TI) leading to improvements in glycemic control are not well understood. OBJECTIVE: To evaluate time to TI in a pharmacist-physician practice model (PPM) as compared with usual medical care (UMC), explore the method and type of antidiabetic TI, and evaluate achievement of hemoglobin A1C (A1C) goal among each cohort. METHODS: This was a retrospective cohort study conducted between January 1, 2017, and December 31, 2018. Median time to TI was calculated and compared between patients in the PPM and UMC groups using the log rank test. Descriptive statistics were used to evaluate the method and type of TI and A1C goal achievement. RESULTS: A total of 56 patients were included. The median (interquartile range) time to antidiabetic TI among the PPM cohort was 37.5 days (8, 216.5), as compared with 142 days (16, 465) in the UMC cohort (P = 0.19). At 1 year post-index date, 25% of patients in the PPM cohort reached their A1C goal compared with 18.8% of patients in the UMC cohort. This effect was maintained in the subgroup (n = 49) of patients receiving TI (23.1% vs 17.8%). CONCLUSION AND RELEVANCE: A shorter time to TI and improvement in A1C goal achievement was observed with pharmacist-physician care compared with UMC. These findings suggest that pharmacist-physician care may be one of several interventions necessary to overcome therapeutic inertia in diabetes care.

Continuous glucose monitoring in persons with type 2 diabetes not using insulin.

INTRODUCTION: CGM is an evidence-based intervention to improve glycemic control in persons with T1D and T2D using insulin. Use of CGM in persons with T2D not using insulin is not well studied. AREAS COVERED: Existing clinical evidence for the use of CGM in persons with T2D is reviewed with a focus on persons with T2D not using insulin. Additional perspective and consideration are provided on the role and rationale for using CGM in persons with T2D not using insulin. EXPERT OPINION: On the basis of available evidence, persons with T2D not using insulin benefit clinically through reduction in HbA1c, and improvement in time in range. Additional benefits include improvement in behavior modification, satisfaction, quality of life, empowerment, and diabetes distress. Drivers of these benefits are independent of insulin use in persons with T2D and may include an improved understanding of how diet, lifestyle, and exercise impact diabetes through CGM use. Clinical benefits from CGM independent of medication use include ability to modify health behavior and subsequently improve self-management.

Prevalence of and Characteristics Associated With Overbasalization Among Patients With Type 2 Diabetes Using Basal Insulin: A Cross-Sectional Study.

This article describes a cross-sectional analysis of 655 patients to determine the prevalence of and patient-specific characteristics associated with overbasalization in patients with type 2 diabetes. Overbasalization was defined as uncontrolled A1C (>8%) plus a basal insulin dose >0.5 units/kg/day. The period prevalence of overbasalization was found to be 38.1, 42.7, and 42% for those with an A1C >8, ≥9, and ≥10%, respectively. Those with an A1C ≥9% had the greatest likelihood of experiencing overbasalization. These results suggest that overbasalization may play a role in patients not achieving optimal glycemic control in type 2 diabetes.

A Review of the First Long-term Implantable Continuous Glucose Monitoring System Available in the United States.

BACKGROUND: Although real-time continuous glucose monitoring (rtCGM) has been shown to improve glycemic control in patients with type 1 diabetes mellitus and type 2 diabetes mellitus treated with insulin, rates of adoption have been low. A novel approach, with the use of a long-term implantable continuous glucose monitoring (LTI CGM) has the potential to overcome barriers to rtCGM. The purpose of this review is to provide a background on the first LTI CGM technology to be approved, along with a review of contraindications, interference, safety, accuracy, and efficacy. Considerations for patient selection are discussed based on the available evidence. METHODS: PubMed, EMBASE, and Cochrane Library were searched for keywords and subject headings to identify studies assessing LTI CGM. RESULTS: Seven studies were identified which assessed LTI CGM. Mean absolute relative difference is similar to available CGM devices. Rates of adverse events were low. Change in hemoglobin A1c with LTI CGM may be comparable to rtCGM. CONCLUSIONS: Based on the available evidence, LTI CGM appears to be safe and accurate. Additional clinical trial investigation is warranted to evaluate the glycemic efficacy of LTI CGM.

Evaluation of cardiovascular and renal outcomes with ertugliflozin: what is the VERdict from the VERTIS-CV trial?

INTRODUCTION: A growing number of antidiabetic agents have demonstrated cardiovascular and renal benefits in cardiovascular outcome trials (CVOTs), despite such trials being principally required to rule out excess cardiovascular risk. AREAS COVERED: This article addresses the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes (VERTIS-CV) trial, its background, design, results, and implications. In patients at least 40 years of age with atherosclerotic cardiovascular disease (ASCVD), the VERTIS-CV trial demonstrated ertugliflozin was non-inferior to placebo for major adverse cardiovascular events, though not superior. Ertugliflozin significantly reduced hospitalization for heart failure compared to placebo. The composite renal outcome was not significantly different between groups. Ertugliflozin was generally well tolerated with a safety profile commensurate with other sodium-glucose co-transporter-2 inhibitors (SGLT-2) inhibitors. EXPERT OPINION: In patients with type 2 diabetes and ASCVD, ertugliflozin appears safe with a noted non-significant trend toward improved renal outcomes. Approximately 23.7% of patients in the VERTIS-CV trial had heart failure, the highest among SGLT-2 inhibitor CVOTs. The VERTIS-CV trial reaffirms the reduction in heart failure hospitalizations as a likely class effect of SGLT-2 inhibitors. While the trial supports the use of ertugliflozin beyond glycemic control, agents with confirmed superiority for improved cardiovascular outcomes and mortality may be preferred.