Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment.

BACKGROUND: It is thought that a reduction in the frequency of basal insulin injections might facilitate treatment acceptance and adherence among patients with type 2 diabetes. Insulin icodec is a basal insulin analogue designed for once-weekly administration that is in development for the treatment of diabetes. METHODS: We conducted a 26-week, randomized, double-blind, double-dummy, phase 2 trial to investigate the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100 in patients who had not previously received long-term insulin treatment and whose type 2 diabetes was inadequately controlled (glycated hemoglobin level, 7.0 to 9.5%) while taking metformin with or without a dipeptidyl peptidase 4 inhibitor. The primary end point was the change in glycated hemoglobin level from baseline to week 26. Safety end points, including episodes of hypoglycemia and insulin-related adverse events, were also evaluated. RESULTS: A total of 247 participants were randomly assigned (1:1) to receive icodec or glargine. Baseline characteristics were similar in the two groups; the mean baseline glycated hemoglobin level was 8.09% in the icodec group and 7.96% in the glargine group. The estimated mean change from baseline in the glycated hemoglobin level was -1.33 percentage points in the icodec group and -1.15 percentage points in the glargine group, to estimated means of 6.69% and 6.87%, respectively, at week 26; the estimated between-group difference in the change from baseline was -0.18 percentage points (95% CI, -0.38 to 0.02, P = 0.08). The observed rates of hypoglycemia with severity of level 2 (blood glucose level, <54 mg per deciliter) or level 3 (severe cognitive impairment) were low (icodec group, 0.53 events per patient-year; glargine group, 0.46 events per patient-year; estimated rate ratio, 1.09; 95% CI, 0.45 to 2.65). There was no between-group difference in insulin-related key adverse events, and rates of hypersensitivity and injection-site reactions were low. Most adverse events were mild, and no serious events were deemed to be related to the trial medications. CONCLUSIONS: Once-weekly treatment with insulin icodec had glucose-lowering efficacy and a safety profile similar to those of once-daily insulin glargine U100 in patients with type 2 diabetes. (Funded by Novo Nordisk; NN1436-4383 ClinicalTrials.gov number, NCT03751657.).

Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor co-agonists for cardioprotection, type 2 diabetes and obesity: a review of mechanisms and clinical data.

PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of type 2 diabetes (T2D) and obesity, and some are recommended for cardiorenal risk reduction in T2D. To enhance the benefits with GLP-RA mono-agonist therapy, GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonists are in development to capitalize on the synergism of GLP-1 and GIP agonism. We review the mechanisms of action and clinical data for GLP-1/GIP receptor co-agonists in T2D and obesity and their potential role in cardiovascular protection. RECENT FINDINGS: Tirzepatide, a first-in-class unimolecular GLP-1/GIP receptor co-agonist, is approved for T2D and is awaiting approval for obesity management. Phase 3 trials in T2D cohorts revealed significant reductions in glycemia and body weight and superiority compared with GLP-1R mono-agonism with semaglutide. Tirzepatide has demonstrated significant body weight reductions in individuals with obesity but not diabetes. It enhances lipid metabolism, reduces blood pressure, and lowers liver fat content. Pooled phase 2/3 data showed cardiovascular safety in T2D while a post hoc analysis suggested tirzepatide slows the decline of kidney function in T2D. SUMMARY: GLP-1/GIP receptor co-agonists are a novel addition to the diabetes and obesity armamentarium. The cardiorenal-metabolic benefits position them as promising multiprong tools for metabolically complex individuals with chronic vascular complications.

IMpact of flash glucose Monitoring in pEople with type 2 Diabetes Inadequately controlled with non-insulin Antihyperglycaemic ThErapy (IMMEDIATE): A randomized controlled trial.

AIM: To examine the efficacy and patient satisfaction of intermittently scanned continuous glucose monitoring (isCGM) in adults using non-insulin therapies for the management of type 2 diabetes. MATERIALS AND METHODS: The IMMEDIATE study was a multisite, open label, randomized controlled trial with follow-up at 16 weeks. Adults with type 2 diabetes using at least one non-insulin therapy, with an HbA1c of 7.5% or higher (≥ 58 mmol/mol), were randomized 1:1 to receive an isCGM device plus diabetes self-management education (isCGM + DSME) or DSME alone. Enrolment occurred from 8 September 2020 to 24 December 2021. The primary outcome was percentage mean time in range (TIR), in the final 2-week period, measured via blinded CGM. RESULTS: One hundred and sixteen participants were randomized (mean age, 58 years; diabetes duration, 10 years; mean HbA1c, 8.6% [70 mmol/mol]). At 16 weeks of follow-up, the isCGM and DSME arm had a significantly greater mean TIR by 9.9% (2.4 hours) (95% CI, -17.3% to -2.5%; P < .01), significantly less time above range by 8.1% (1.9 hours) (95% CI, 0.5% to 15.7%; P = .037), and a greater reduction in mean HbA1c by 0.3% (3 mmol/mol) (95% CI, 0% to 0.7%; P = .048) versus the DSME arm. Time below range was low and not significantly different between groups and hypoglycaemic events were few in both groups. Glucose monitoring satisfaction was higher among isCGM users (adjusted difference -0.5 [95% CI, -0.7 to -0.3], P < .01). CONCLUSIONS: The IMMEDIATE study has shown that among non-insulin-treated individuals with type 2 diabetes, use of isCGM is associated with an improvement in glycaemic outcomes.

The Use of High-Dose Corticosteroids Versus Low-Dose Corticosteroids With and Without Tocilizumab in COVID-19 Acute Respiratory Distress Syndrome.

BACKGROUND: Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS: This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS: In this cohort, 110 (54%) and 95 (46%) patients received high-dose (≥10 mg dexamethasone equivalent) and low-dose (<10 mg dexamethasone equivalent) corticosteroids for more than 3 consecutive days, respectively. Thirty-five patients (32%) in the high-dose group and 33 patients (35%) in the low-dose group survived to hospital discharge (P = 0.85). There was no difference in 28-day mortality in patients who received high-dose corticosteroids without tocilizumab compared with those who received low-dose corticosteroids with tocilizumab (n = 38/82, 46% vs n = 19/40, 48% P = 0.99); however, there was a higher mortality if patients received low-dose corticosteroids without tocilizumab (n = 39/55, 71%, P = 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS: In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.

Benefits of GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists for Stroke Reduction in Type 2 Diabetes: A Call to Action for Neurologists.

People living with diabetes are at higher risk for stroke and have a poorer prognosis following a stroke event than those without diabetes. Data from cardiovascular outcome trials and meta-analyses indicate that GLP-1RAs (glucagon-like peptide 1 receptor agonists) reduce the risk of stroke in individuals with type 2 diabetes. Accordingly, many guidelines now recommend the addition of GLP-1RAs to ongoing antihyperglycemic regimens to lower the risk of stroke in type 2 diabetes. The current work summarizes evidence supporting the use of GLP-1RAs for stroke reduction in people with type 2 diabetes and offers 2 new resources for neurologists who are considering GLP-1RAs for their patients-a list of frequently asked questions with evidence-based answers on safely initiating and managing GLP-1RAs, and a practical decision-making algorithm to assist in using GLP-1RAs as part of a stroke reduction strategy.

Percutaneous Dilational Tracheostomy for Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation.

OBJECTIVES: To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers. DESIGN: Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis. SETTING: Critical care units at two large metropolitan hospitals in New York City. PATIENTS: Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation. INTERVENTIONS: Bedside percutaneous dilational tracheostomy with modified visualization and ventilation. MEASUREMENTS AND MAIN RESULTS: Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7-12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16-24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34-5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06-0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01-2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, -15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS: In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes.

The role of icosapent ethyl in cardiovascular risk reduction.

PURPOSE OF REVIEW: Elevated levels of triglycerides, independent of low-density lipoprotein cholesterol (LDL-C) levels and statin therapy, are associated with heightened cardiovascular risk. RECENT FINDINGS: Mixed omega-3 fatty acid formulations, which contain varying amounts of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), lower triglycerides levels but trial results with omega-3 fatty acids combinations have generally been neutral for cardiovascular outcomes. In contrast, the REDUCE-IT trial with icosapent ethyl (IPE), a highly purified ethyl ester of EPA, demonstrated reduced cardiovascular risk in individuals with established atherosclerotic cardiovascular disease or diabetes with at least one additional risk factor, despite having relatively well controlled LDL-C levels but triglycerides at least 135 mg/dl while on statin therapy. IPE offers an important new avenue for cardiovascular risk management in statin-treated individuals with elevated triglycerides. SUMMARY: This review summarizes the results from outcome trials conducted with omega-3 fatty acids, differentiating between those with combinations of EPA/DHA and those with pure EPA, as well as imaging and preclinical data that help explain the different cardiovascular efficacy observed. A list of frequently asked questions with evidence-based responses is provided to assist our colleagues and their patients in the shared-decision process when considering if IPE is appropriate for cardiovascular risk reduction.

Effect of insulin degludec versus insulin glargine U100 on time in range: SWITCH PRO, a crossover study of basal insulin-treated adults with type 2 diabetes and risk factors for hypoglycaemia.

AIMS: To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes. MATERIALS AND METHODS: We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin-treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16-week titration and 2-week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once-weekly titration (target: 3.9-5.0 mmol/L) was based on pre-breakfast self-measured blood glucose. The primary endpoint was percentage of TIR (3.9─10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9-7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels. RESULTS: At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD -0.88% [95% CI: -1.34, -0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed. CONCLUSIONS: Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin-treated people with type 2 diabetes.

Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19.

OBJECTIVE: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), any thrombotic event (19.4% versus 10.2%; adjusted odds ratio, 1.9 [95% CI, 1.4-2.6]; P<0.001), acute kidney injury (42.4% versus 19.0%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), and death (29.9% versus 10.8%; adjusted odds ratio, 2.1 [95% CI, 1.6-2.9]; P<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

Pulmonary Embolism Response Team activation during the COVID-19 pandemic in a New York City Academic Hospital: a retrospective cohort analysis.

Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism Response Teams (PERT) have previously been associated with improved outcomes. We aimed to investigate whether PERT utilization, recommendations, and outcomes for patients diagnosed with acute PE changed during the COVID-19 pandemic. This is a retrospective cohort study of all adult patients with acute PE who received care at an academic hospital system in New York City between March 1st and April 30th, 2020. These patients were compared against historic controls between March 1st and April 30th, 2019. PE severity, PERT utilization, initial management, PERT recommendations, and outcomes were compared. There were more cases of PE during the pandemic (82 vs. 59), but less PERT activations (26.8% vs. 64.4%, p < 0.001) despite similar markers of PE severity. PERT recommendations were similar before and during the pandemic; anticoagulation was most recommended (89.5% vs. 86.4%, p = 0.70). During the pandemic, those with PERT activations were more likely to be female (63.6% vs. 31.7%, p = 0.01), have a history of DVT/PE (22.7% vs. 1.7%, p = 0.01), and to be SARS-CoV-2 PCR negative (68.2% vs. 38.3% p = 0.02). PERT activation during the pandemic is associated with decreased length of stay (7.7 ± 7.7 vs. 13.2 ± 12.7 days, p = 0.02). PERT utilization decreased during the COVID-19 pandemic and its activation was associated with different biases. PERT recommendations and outcomes were similar before and during the pandemic, and led to decreased length of stay during the pandemic.

Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial.

BACKGROUND: SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease. METHODS: Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m2. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide). RESULTS: Among the 97 participants (90 men [93%], mean [standard deviation] age 62.8 [9.0] years, type 2 diabetes mellitus duration 11.0 [8.2] years, estimated glomerular filtration rate 88.4 [16.9] mL/min/1.73m2, LV mass indexed to body surface area 60.7 [11.9] g/m2), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m2 and 0.01 g/m2 for those assigned empagliflozin and placebo, respectively (adjusted difference -3.35 g/m2; 95% CI, -5.9 to -0.81g/m2, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference -6.8mmHg, 95% CI -11.2 to -2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference -3.2mmHg; 95% CI, -5.8 to -0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003). CONCLUSIONS: Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition with empagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02998970.

Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials.

Sodium-glucose cotransporter 2 inhibitors and type 2 diabetes: clinical pearls for in-hospital initiation, in-hospital management, and postdischarge.

PURPOSE OF REVIEW: The aim of this article is to provide practical recommendations on safe initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors to in-patients as well as management of those who are already on SGLT2 inhibitors. RECENT FINDINGS: Robust data from stable outpatient cohorts indicate that the SGLT2 inhibitors are associated with clinically meaningful reductions in major adverse cardiovascular events, lower rates of hospitalization for heart failure, and a reduction in major kidney outcomes There is however a lack of information on how to initiate and manage SGLT2 inhibitors in an acute in-patient setting. SUMMARY: SGLT2 inhibitors may be cautiously appropriate for in-patients if all the criteria for safe use are met but good clinical judgment must prevail. Temporary withholding of SGLT2 inhibitors is appropriate in hospitalized patients during a period of stress and/or insulinopenia.

Low left ventricular outflow tract velocity time integral is associated with poor outcomes in acute pulmonary embolism.

The left ventricular outflow tract (LVOT) velocity time integral (VTI) is an easily measured echocardiographic stroke volume index analog. Low values predict adverse outcomes in left ventricular failure. We postulate the left ventricular VTI may be a signal of right ventricular dysfunction in acute pulmonary embolism, and therefore a predictor of poor outcomes. We retrospectively reviewed echocardiograms on all Pulmonary Embolism Response Team activations at our institution at the time of pulmonary embolism diagnosis. Low LVOT VTI was defined as ⩽ 15 cm. We examined two composite outcomes: (1) in-hospital death or cardiac arrest; and (2) shock or need for primary reperfusion therapies. Sixty-one of 188 patients (32%) had a LVOT VTI of ⩽ 15 cm. Low VTI was associated with in-hospital death or cardiac arrest (odds ratio (OR) 6, 95% CI 2, 17.9; p = 0.0014) and shock or need for reperfusion (OR 23.3, 95% CI 6.6, 82.1; p < 0.0001). In a multivariable model, LVOT VTI ⩽ 15 remained significant for death or cardiac arrest (OR 3.48, 95% CI 1.02, 11.9; p = 0.047) and for shock or need for reperfusion (OR 8.12, 95% CI 1.62, 40.66; p = 0.011). Among intermediate-high-risk patients, low VTI was the only variable associated with the composite outcome of death, cardiac arrest, shock, or need for reperfusion (OR 14, 95% CI 1.7, 118.4; p = 0.015). LVOT VTI is associated with adverse short-term outcomes in acute pulmonary embolism. The VTI may help risk stratify patients with intermediate-high-risk pulmonary embolism.

Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol.

Recent phase 3 clinical trials have evaluated the impact of adding sodium-glucose co-transporter (SGLT) inhibitors to the type 1 diabetes armamentarium. These trials studied SGLT2 inhibitors (dapagliflozin and empagliflozin) and a dual SGLT1 and SGLT2 inhibitor (sotagliflozin), and demonstrated that these oral non-insulin antihyperglycaemic medications are able not only to improve glycaemic control, but also to reduce body weight and extend time in range without increasing rates of hypoglycaemia in type 1 diabetes. Diabetic ketoacidosis (DKA) is a feature of type 1 diabetes and the risk is increased when SGLT inhibitors are used in type 1 diabetes. To minimize the risk of DKA and still gain the multiple benefits, we developed the "STOP DKA Protocol ", an easily accessible and practical tool, that provides a risk mitigation strategy for reducing DKA in patients with type 1 diabetes being treated with SGLT inhibitors.

Evaluation of Pharmacy-Developed Antibiotic Desensitization Protocols.

BACKGROUND: Parameters within reconstitution, storage, stability, and administration may be optimized according to the unique pharmacokinetics of each antibiotic to ensure a successful desensitization. OBJECTIVE: The study aims to evaluate the successfulness and safety of antibiotic desensitization protocols developed by the pharmacy department at our institution. METHODS: A retrospective study was conducted at an 800-bed, urban, tertiary care, academic medical center. A total of 36 patients 18 years of age or older, admitted to our intensive care units between March 2013 and July 2017, who underwent antibiotic desensitization utilizing our pharmacy developed protocols were included. RESULTS: In 36 patients, 61 desensitization cases were identified and included; 17 (47%) were male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In all, 15 different antibiotics were administered for desensitization, with meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7, 11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61 desensitizations were completed successfully with or without experiencing reactions, and 53 (89%) of the successful desensitization cases were completed without reactions. Two cases were categorized as anaphylaxis, which was severe enough to terminate the desensitization process. Of the 59 cases successfully completed, the 6 (10%) cases that experienced reactions were managed successfully during desensitization with completion of the process. Conclusion and Relevance: The findings suggest that our pharmacy-developed antibiotic desensitization protocols are successful and safe and may be adapted by other institutions.

A practical approach and algorithm for intensifying beyond basal insulin in type 2 diabetes.

Despite the availability of long-term data demonstrating the benefits of timely and aggressive intensification of antihyperglycaemic regimens among individuals with type 2 diabetes, intensification beyond basal insulin continues to be suboptimal and a global challenge. This review summarizes the evidence surrounding the various options of advancing glucose-lowering management beyond basal insulin and provides a practical algorithm to assist in optimizing patient care and enhancing glycaemic target achievements.