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Insulin Detemir Versus Insulin Glargine in the Hospital: Do Hypoglycemia Rates Differ? Michelle A

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Insulin Detemir Versus Insulin Glargine in the Hospital: Do Hypoglycemia Rates Differ? Michelle A Insulin Detemir Versus Insulin Glargine in the Hospital: Do Hypoglycemia Rates Differ? Michelle A. Crisher,1 Christopher A. Giuliano,1,2 and Carrie L. Hartner1 FEATURE ARTICLE FEATURE ■ IN BRIEF Several studies have compared the safety and efficacy of insulin detemir and insulin glargine; however, most have been conducted in the ambulatory care setting. This retrospective cohort study compared hypoglycemia rates between the two basal insulin analogs in hospitalized patients with diabetes. No difference was found between the two insulin cohorts in the proportion of patients who experienced hypoglycemic events. n 2015, it was estimated that ~30.3 Detemir is also derived using recom- million Americans were living binant technology and, when injected, Iwith type 1 or type 2 diabetes (1). forms a soluble depot. In addi- Common long-term complications tion, acylation and self-association of uncontrolled diabetes include properties of detemir allow for end-stage renal disease, diabetic reti- reversible binding to albumin, which nopathy, amputations, and increased results in its prolonged duration of hospitalizations (2,3). In the inpatient action. Detemir’s duration of action setting, hyperglycemia, hypoglycemia, on blood glucose varies from 6 to 23 and blood glucose variability can lead hours and is largely dose dependent, to increased costs, lengths of stay, and with longer duration observed as mortality (4,5). Long-acting insulin dosage increases (6,9). Glargine and analogs remain one of the mainstays detemir may be administered once of therapy in the management of or twice daily depending on medica- blood glucose in patients with diabe- tion and patient considerations (8,9). tes (5). Two commonly used basal in- These can include basal insulin dose, sulin analogs are insulin glargine and prandial insulin use, glycemic target, insulin detemir. patient preference, and endogenous Detemir and glargine exhibit insulin reserve (10–12). similar pharmacokinetic and phar- Studies comparing the safety and macodynamic profiles, which make efficacy of detemir and glargine have them appropriate for basal therapy. been done mostly in the ambulatory 1Ascension St. John Hospital, Detroit, MI Both demonstrate a peakless time- care setting and have demonstrated action profile and a long duration of similar glycemic control when added 2Wayne State University Eugene Applebaum College of Pharmacy and action, although they achieve this to mealtime insulin or oral medica- Health Sciences, Detroit, MI through different absorption mecha- tions in patients with type 2 diabetes Corresponding author: Christopher A. nisms (6,7). Glargine is derived using (13,14). In contrast, a subgroup of Giuliano, [email protected] recombinant technology and forms the PREDICTIVE study (15) found https://doi.org/10.2337/cd18-0065 a precipitate that dissolves slowly at improvements in glycemic control physiologic pH, thus delaying absorp- and a reduction of hypoglycemic ©2018 by the American Diabetes Association. Readers may use this article as long as the work tion. This delayed absorption allows events when switching patients is properly cited, the use is educational and not for a duration of action that ranges with type 1 or type 2 diabetes from for profit, and the work is not altered. See http:// creativecommons.org/licenses/by-nc-nd/3.0 from 10 to 24 hours, reaching up glargine to detemir at routinely for details. to ~30 hours in a few studies (6,8). scheduled clinic visits (15). CLINICAL DIABETES 1 Clinical Diabetes Online Ahead of Print, published online October 17, 2018 FEATURE ARTICLE Despite the breadth of compar- cause a transition of preferred formu- Outcomes ative literature surrounding basal lary agent (from glargine to detemir) The primary outcome was the pro- insulin therapy in the ambulatory occurred during this time. Patients portion of patients who experienced care environment, there is a paucity were identified via active orders for hypoglycemia within 72 hours of evidence comparing the safety either detemir or glargine within the of initiating detemir or glargine. and efficacy of glargine and detemir electronic medical record (EMR) sys- Hypoglycemia was defined as a blood in hospitalized patients. Galindo et tem. EMRs of adult patients with a glucose value <70 mg/dL. Secondary al. (16) performed a retrospective diagnosis of diabetes and an order outcomes included the proportion database analysis of glargine and for detemir or glargine were reviewed of patients who experienced hyper- detemir use in hospitalized patients for inclusion. Patients were excluded glycemic events, the total number of who had either type 1 or type 2 dia- if they were pregnant, had received hypoglycemic events, and total in- betes. No difference in average blood a continuous insulin infusion, had sulin requirements within 72 hours glucose values was noted between the received detemir or glargine for <72 of detemir or glargine initiation. two insulin cohorts throughout the hours, were admitted to an intensive Hyperglycemia was defined as a blood > hospital stay. Similarly, there were care unit (ICU), or had missing data glucose value 180 mg/dL. no differences in maximum blood needed for analysis (missing both Data Analysis glucose or number of patients with height and weight, having no blood Our sample size was based on an severe hyperglycemia. Interestingly, glucose measurements, or missing se- overall rate of hypoglycemia in the there was an increase in hypoglyce- rum creatinine [SCr] values) within detemir group of 33.5% compared to mic events in the detemir cohort. 29% for the glargine group, with an Patients who received detemir also 72 hours of initiation of either de- alpha error rate of 0.05 and 80% pow- received higher total daily doses temir or glargine. Institutional review er (16). To find this difference, a sam- (TDDs) of insulin, as well as more board approval was obtained before ple size of 1,659 patients per group daily injections. In contrast, Zhang the study commenced. was needed, for a total of 3,318 pa- et al. (17) performed a prospective Data Collection tients. Data were analyzed using SPSS randomized crossover trial comparing Data were electronically abstract- version 25.0 software (IBM Corp., glargine and detemir in hospital- ed from the EMR system using Armonk, N.Y.). Descriptive data were ized patients with type 2 diabetes. Access 2016 software (Microsoft expressed as mean ± SD, median ± The authors concluded that the two Corp., Redmond, Wash.) to ex- interquartile range, or frequency and insulins demonstrated similar time tract International Classification of percentage. Univariate analysis was to fasting blood glucose target and Diseases 9th or 10th revision codes performed using a Student t test, a similar TDDs. Hypoglycemic events and Excel 2016 software (Microsoft Mann Whitney U test, or a χ2 test for occurred in three of the patients Corp, Redmond, Wash.) to extract continuous, ordinal, and categorical switched to detemir. However, this all other data. Authors M.A.C. and data, respectively. Multivariate logistic analysis was limited to 42 patients, C.A.G. organized the extracted data. regression was performed using hypo- thus restricting its power to detect Data collected within 72 hours of de- glycemia as the dependent variable. safety events of statistical significance. temir or glargine initiation included Variables were initially considered for More evidence comparing glargine highest and lowest creatinine clear- inclusion into the model if there was and detemir in the inpatient environ- a difference between the detemir and ment is necessary. The purpose of this ance, all blood glucose values, short- glargine groups and there was an asso- study was to compare the efficacy and acting insulin, sliding scale type, insu- ciation with hypoglycemia (P < 0.1). safety profiles of glargine and detemir lin TDD, nothing-by-mouth status, by exploring the incidence of both acute kidney injury, chronic kidney Results hypoglycemia and hyperglycemia in disease, corticosteroids, beta-blockers, Of the 5,200 patients initially hospitalized patients with diabetes. total parenteral nutrition, enteral screened, 3,726 were identified for nutrition, and specific infections, Design and Methods inclusion. A total of 3,318 patients including urinary tract infection, (1,659 in each cohort) were randomly Sample Selection pneumonia, bacteremia, and diabetic selected for the final data analysis. The This retrospective cohort study was foot infection. Data collected outside most common reason for exclusion conducted at a 772-bed community of 72 hours included baseline demo- was no diagnosis of diabetes. Figure teaching hospital in patients with a graphics, length of stay, long-acting 1 shows an inclusion and exclusion diagnosis of type 1 or type 2 diabetes insulin taken before admission, and flowchart. Baseline characteristics between January 2010 to November most recent A1C. Electronically ab- are summarized in Table 1 and were 2017. Data from the month of stracted data were manually validated mostly similar between the two co- December 2013 were not collected be- by examining 50 patients per cohort. horts. The detemir cohort included 2 CLINICAL.DIABETESJOURNALS.ORG Clinical Diabetes Online Ahead of Print, published online October 17, 2018 CRISHER ET AL . confounders, multivariate regression analysis was performed (Table 2). Age, baseline SCr, high-intensity insulin scale, and concomitant cor- ticosteroid use all met criteria to be included in the final model. When controlling
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