Understanding the Pharmacokinetics and Glucodynamics of Once Weekly Basal Insulins to Inform Dosing Principles: An Introduction to Clinicians.

OBJECTIVE: A new generation of basal insulin analogs enabling once-weekly administration is currently under development. Weekly basal insulins have the potential to overcome limitations exhibited by current daily basal insulins. The pharmacokinetic and glucodynamic characteristics differ significantly between weekly and daily basal insulins and will require paradigm shifts in how basal insulins are dosed. METHODS: An overview of pharmacokinetic and glucodynamic principles of basal insulins is presented. Specifically, the pharmacokinetic and glucodynamic properties of daily basal insulins and how these differ for the new weekly basal insulins are discussed. Finally, models and simulations are used to describe the impact of weekly insulin properties on dosing. RESULTS: Two approaches have been used to extend the half-lives of these insulins, creating fusion proteins with reduced clearance and reduced receptor-mediated degradation of the insulin. The resulting prolonged exposure-response profiles affect dosing and the impact of dosing errors. Specifically, the impact of loading doses, missed doses, and double doses, and the effect on glycemic variability of a once weekly basal insulin option are demonstrated using pharmacokinetic/glucodynamic models and simulations. CONCLUSIONS: The transition from daily to weekly basal insulin dosing requires an understanding of the implications of the prolonged exposure-response profiles to effectively and confidently incorporate these weekly basal insulins into clinical practice. By reviewing the application of pharmacokinetic and glucodynamic principles to daily basal insulin analogs, the differences with weekly basal insulins, and the impact of these properties on dosing, this review intends to explain the principles behind weekly basal insulin dosing.

Association between continuous glucose monitoring metrics and clinical outcomes in adults with type 1 diabetes in a real-world setting.

AIMS: Continuous glucose monitoring (CGM) metrics can assist diabetes management. Consensus statements recommend > 70 % time in range (TIR) and ≤ 36 % glucose coefficient of variation (CV). However, how these targets perform in clinical practice is unknown. This retrospective, longitudinal cohort study analyzed relationships between TIR, CV, glycated hemoglobin (HbA1c), and hypoglycemia in a real-world setting. METHODS: Data of 542 adults with type 1 diabetes who used CGM (January 2014-July 2020) were analyzed. Associations between TIR and HbA1c at the same and subsequent visits, incidence rate ratios (IRRs) for hypoglycemia at different CVs, and number of hypoglycemic events at cross-sections of HbA1c and CV were estimated by regression. RESULTS: TIR was inversely related to HbA1c; for every 10 % increase in TIR, HbA1c was significantly reduced by 0.34 % (4 mmol/mol) and 0.20 % (2 mmol/mol) at the same and subsequent visits, respectively. Level 2 hypoglycemia was significantly reduced at CV < 30 %, 30-33 %, 33.1-36 %, and 36.1-40 %: adjusted IRRs vs CV ≥ 40.1 % of 0.14, 0.28, 0.32, and 0.50, respectively. Hypoglycemic events were reduced at lower CV across HbA1c levels and at higher HbA1c across CV levels. CONCLUSION: This study quantifies HbA1c improvements with increased TIR and hypoglycemia reductions with improved CV in clinical practice.

The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa.

Basal insulin continues to be a vital part of therapy for many people with diabetes. First attempts to prolong the duration of insulin formulations were through the development of suspensions that required homogenization prior to injection. These insulins, which required once- or twice-daily injections, introduced wide variations in insulin exposure contributing to unpredictable effects on glycemia. Advances over the last 2 decades have resulted in long-acting, soluble basal insulin analogues with prolonged and less variable pharmacokinetic exposure, improving their efficacy and safety, notably by reducing nocturnal hypoglycemia. However, adherence and persistence with once-daily basal insulin treatment remains low for many reasons including hypoglycemia concerns and treatment burden. A soluble basal insulin with a longer and flatter exposure profile could reduce pharmacodynamic variability, potentially reducing hypoglycemia, have similar efficacy to once-daily basal insulins, simplify dosing regimens, and improve treatment adherence. Insulin icodec (Novo Nordisk) and insulin efsitora alfa (basal insulin Fc [BIF], Eli Lilly and Company) are 2 such insulins designed for once-weekly administration, which have the potential to provide a further advance in basal insulin replacement. Icodec and efsitora phase 2 clinical trials, as well as data from the phase 3 icodec program indicate that once-weekly insulins provide comparable glycemic control to once-daily analogues, with a similar risk of hypoglycemia. This manuscript details the technology used in the development of once-weekly basal insulins. It highlights the clinical rationale and potential benefits of these weekly insulins while also discussing the limitations and challenges these molecules could pose in clinical practice.

Real-World Patterns of Basal Insulin Use with Other Diabetes Medications Among People with Type 2 Diabetes Between 2014 and 2020.

INTRODUCTION: Basal insulin's position in the type 2 diabetes (T2D) treatment paradigm has undergone significant revisions since the advent of diabetes medications such as glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is), which offer cardiorenal protection for people with T2D (PwT2D). This study aimed to characterize the demographic, clinical, and diabetes medication utilization patterns of PwT2D initiating basal insulin between 2014 and 2020 over the time period when these revisions were occurring. METHODS: A retrospective study was conducted using the IBM® MarketScan® databases and included adults with T2D who initiated basal insulin therapy (basal insulin initiators) in 2015, 2017, or 2019. Patient characteristics, medication utilization patterns, and time to add an additional diabetes drug class were compared across years. Characteristics of users of basal insulin-GLP-1RA combination therapy (GLP-1RA-basal insulin dual users) were also compared across years. RESULTS: Between 2015 and 2019, initiation of basal insulin therapy remained steady, with 1.6-1.9% of PwT2D starting basal insulin in each year. GLP-1RA and SGLT-2i use increased pre- and post-basal insulin initiation (pre-basal: GLP-1RA, from 14.8% to 25.2%, p < 0.0001; SGLT-2i, from 11.4% to 20.5%, p < 0.0001; post-basal: GLP-1RA, from 16.7% to 30.5%, p < 0.0001; SGLT-2i, from 13.4% to 23.3%, p < 0.0001]). The proportion of PwT2D with underlying cardiovascular and renal diseases did not increase during this period. Among basal insulin initiators without prior GLP-1RA, SGLT-2i, or bolus insulin use, time to adding on these agents decreased, with 14.0-15.6% starting bolus insulin within the first year. Among GLP-1RA-basal insulin dual initiators, the proportion of those with underlying cardiovascular disease was not higher among GLP-1RA first users. CONCLUSIONS: In this real-world study, insulin remained key in the T2D treatment paradigm. A growing proportion of PwT2D utilized GLP-1RAs and SGLT-2is before and after initiation of basal insulin therapy. At the same time, there was no increase in the proportion of those initiating basal insulin who had cardiorenal comorbidity profiles for which treatment guidelines have recommended the use of GLP-1RAs or SGLT-2is.

What is the value of faster acting prandial insulin? Focus on ultra rapid lispro.

Rapid-acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra-rapid-acting insulins, including ultra-rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head-to-head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.

Trends in U.S. Insulin Use and Glucose Monitoring for People with Diabetes: 2009-2018.

BACKGROUND: The delivery and administration of insulin has undergone many changes over the years. This research examines U.S. trends in insulin use among people with type 1 diabetes (T1D) or type 2 diabetes (T2D) in the U.S. from 2009 to 2018. METHODS: The IBM® MarketScan® Commercial and Medicare databases were used to identify trends in insulin use over 10 years. The study included people with T1D or T2D who filled a prescription for insulin in any calendar year from 2009 to 2018. The analyses examined insulin regimen and delivery and the use of glucose monitoring systems. Generalized estimating equations were used to test whether trends were statistically significant. RESULTS: Individuals with T1D were most commonly prescribed a basal and bolus insulin regimen or short/rapid insulin only, while for people with T2D the use of basal-only insulin increased significantly over the study period. In both groups there was a significant decline in the use of premix insulin from 2009 to 2018. Insulin pump use increased for individuals with T1D, while disposable pen use increased for people in both cohorts. In both cohorts, there was a statistically significant increase in the use of continuous glucose monitoring, although this increase was more pronounced and occurred earlier among individuals with T1D. CONCLUSIONS: Results indicate significant changes in insulin regimens and delivery and glucose monitoring from 2009 to 2018. These findings suggest that insulin prescribing continues to change in response to the development of new therapeutics, advances in insulin delivery technology, and glucose monitoring systems.

Treatment patterns and outcomes before and after human regular U-500 insulin initiation via KwikPen® among US veterans with type 2 diabetes mellitus.

INTRODUCTION: A dedicated Humulin R U-500 (U-500R) prefilled disposable insulin pen (KwikPen) became available in 2016, yet limited evidence exists on treatment patterns and outcomes of U-500R via KwikPen (U500-KP). METHODS: This is a retrospective observational study among adults with ≥2 claims for type 2 diabetes initiating U500-KP (index date: first claim) identified in Veterans Health Administration database. Treatment patterns and outcomes were evaluated in 9-month pre- and post-index periods, including dispensed total daily insulin dosage derived from claims expressed in units (dTDD) and units/kg, HbA1c, symptomatic hypoglycemia, and body weight. Multivariable modeling was used to confirm the associations between U500-KP initiation and outcomes. RESULTS: A total of 647 U500-KP initiators were identified. The mean age was 64 years, and mean Quan-Charlson Comorbidity-index score was 3.8. Before U500-KP initiation, 62% of patients had dTDD ≤ 200 units with mean A1c 9.5%. Mean dTDD increased from 188.2 to 269.9 units after U500-KP initiation with mean A1c decreased by 0.83% (SD = 1.67) and mean weight gain of 1.5 kg (SD = 6.74). Hypoglycemia events increased from 4.3 to 5.3 (p < 0.05) per person per year. CONCLUSIONS: Initiation of U500-KP brought significant improvement in dispensed insulin dose and glycemic control accompanied by moderate increases in hypoglycemia and weight.

The Effect of Prestudy Insulin Therapy on Safety and Efficacy of Human Regular U-500 Insulin by Pump or Injection: A Posthoc Analysis.

OBJECTIVE: We conducted a posthoc analysis of the VIVID study (Safety and Efficacy of Human Regular U-500 Insulin Administered by Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections in Subjects With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Parallel Clinical Trial), comparing 2 delivery methods of human regular U-500 insulin (U-500R), continuous subcutaneous insulin infusion (CSII) versus multiple daily injection (MDI), in type 2 diabetes requiring high insulin, to determine influence of prestudy insulin on glycemic outcomes. METHODS: We compared A1C, total daily insulin dose (TDD), weight, and hypoglycemia by subgroups of prestudy insulin (prestudy U-500R vs non-U-500R) and treatment (CSII vs MDI). RESULTS: At baseline, prestudy U-500R had higher TDD, higher body mass index, lower A1C and fasting plasma glucose, and higher rate of hypoglycemia compared to non-U-500R. Active titration of U-500R reduced A1C in both subgroups, with maximum benefit at 8 weeks. At 26 weeks, CSII provided the greatest reduction in A1C in both subgroups, with a greater reduction in non-U-500R. MDI provided an A1C reduction in both subgroups, with the greater reduction in non-U-500R. At 8 weeks, prestudy U-500R reached its lowest A1C; thereafter, A1C rebounded with MDI and remained stable with CSII. In non-U-500R, A1C continued to decrease to study end. In non-U-500R, hypoglycemia increased during active titration, but then decreased in the posttitration maintenance period. In both subgroups, TDD increased from baseline with MDI but not with CSII. Body weight increased in both subgroups but was greater in prestudy U-500R with CSII compared to MDI. CONCLUSION: Regardless of previous insulin, people on high-dose insulin could lower A1C with U-500R, with additional benefit from CSII. These results may provide guidance for use of U-500R in clinical practice.

Treatment Patterns, Adherence, and Persistence Associated With Human Regular U-500 Insulin: A Real-World Evidence Study.

OBJECTIVE | Human regular U-500 insulin (U-500R) is concentrated insulin with basal and prandial activity that can be used as insulin monotherapy. The goal of this study was to better understand treatment patterns (total daily dose [TDD] and concomitant medications), adherence, and persistence in real-world patients treated with U-500R. DESIGN AND METHODS | We selected patients from the Truven Health MarketScan database who initiated U-500R between 2010 and 2013. We collected data for three periods: pre-index (12 months before initiation), post-index (12 months after initiation or until a gap of ≥60 days in U-500R claims), and follow-up (12 months after post-index). Data were analyzed using descriptive statistics and a regression model as appropriate. RESULTS | We identified 1,582 patients who met the selection criteria. The median TDD of U-500R during the post-index period was 333 units/day, with 70.0% of patients using 300-400 units/day. During the post-index period, 74.1% of patients had U-500R claims that did not overlap with prescriptions for other insulins, interpreted as U-500R monotherapy. Among patients with ≥1 U-500R fill in the post-index period (n = 1,208), 54.4% had a medication possession ratio (MPR, a measure of adherence) ≥80%. Although 849 patients had a gap of ≥60 days in U-500R claims in the post-index period, 602 of those resumed U-500R in the follow-up period. Of the 733 patients who had no gap in U-500R claims in the post-index period, 286 had a gap of ≥60 days in claims in year 2, and 447 continued with U-500R treatment beyond 2 years. CONCLUSION | These results demonstrate that U-500R was commonly used as insulin monotherapy, with a median TDD >300 units/day. Compared with published, relevant studies of other insulins, U-500R showed similar or greater adherence and persistence rates. These new data may help guide clinical decision-making when choosing insulin therapy for patients requiring high doses of insulin.

The Evolution of Insulin and How it Informs Therapy and Treatment Choices.

Insulin has been available for the treatment of diabetes for almost a century, and the variety of insulin choices today represents many years of discovery and innovation. Insulin has gone from poorly defined extracts of animal pancreata to pure and precisely controlled formulations that can be prescribed and administered with high accuracy and predictability of action. Modifications of the insulin formulation and of the insulin molecule itself have made it possible to approximate the natural endogenous insulin response. Insulin and insulin formulations had to be designed to produce either a constant low basal level of insulin or the spikes of insulin released in response to meals. We discuss how the biochemical properties of endogenous insulin were exploited to either shorten or extend the time-action profiles of injectable insulins by varying the pharmacokinetics (time for appearance of insulin in the blood after injection) and pharmacodynamics (time-dependent changes in blood sugar after injection). This has resulted in rapid-acting, short-acting, intermediate-acting, and long-acting insulins, as well as mixtures and concentrated formulations. An understanding of how various insulins and formulations were designed to solve the challenges of insulin replacement will assist clinicians in meeting the needs of their individual patients.

Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis.

AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies. RESULTS: Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted. CONCLUSIONS: Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.

Insulin tactics in type 2 diabetes.

Insulin is the most powerful glycemic control agent available. However, its use as a therapeutic modality requires education of the patient and regimentation of food intake, exercise, and frequent glucose monitoring. Such regimentation is particularly important when using a basal-bolus therapy approach. The introduction of many novel noninsulin drugs in the past decade has resulted in better glycemic control and often a need to reduce previously instituted insulin therapy. Although many of these novel therapies by themselves do not cause hypoglycemia, by reducing the overall glycemic burden through a myriad of mechanisms, they function in an insulin-sparing fashion. The doses of exogenously administered insulin may therefore need to be reduced in the presence of these new drugs to mitigate hypoglycemia. For insulin therapy (or any other drug treatment) to be successful, it is critical that the physician not only establish glycemic goals, but communicate these goals to the patient. The measurement of HbA1c helps in achieving a long-term goal, but on a day-today basis, patients need to be cognizant of their own BG goals and what they need to do if falling outside of target. The patients' understanding of self-management skills and empowerment are therefore foundational to insulin therapy.

A case of calciphylaxis in a patient with hypoparathyroidism and normal renal function.

OBJECTIVE: To present the case of a patient with a history of thyroid cancer, postsurgical hypoparathyroidism, chronic calcitriol use, and normal renal function who presented with painful skin lesions secondary to calciphylaxis. METHODS: We describe the history, biochemistry, histopathology, evaluation, and management of this patient. RESULTS: A 47-year-old female with hypoparathyroidism, chronically treated with calcitriol and calcium, presented with exquisitely painful skin ulcerations. Four months prior to the onset of symptoms, she had initiated warfarin therapy for atrial fibrillation. Review of laboratory data from the past year revealed elevated calcium and phosphorus levels. A diagnosis of calciphylaxis was made based upon pathologic evaluation of a skin biopsy. Management included titration of calcitriol and calcium to maintain serum calcium and phosphate levels in the low-normal range. Sodium thiosulfate was administered at a dose of 25 mg intravenously 3 times a week with some resolution in the patient's pain. Unfortunately, the patient battled recurrent bacteremia and sepsis, presumably related to her calciphylaxis wounds, and ultimately succumbed to complications from sepsis. CONCLUSION: Although calciphylaxis is typically associated with renal insufficiency and secondary hyperparathyroidism, we highlight the case of a patient with normal renal function and hypoparathyroidism. Patients treated with chronic calcitriol should have serum calcium and phosphorus monitored closely and may benefit from non-calcium-based phosphate binders if hyperphosphatemia becomes unavoidable. This is especially important in the presence of other risk factors for calciphylaxis, including warfarin use.

The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial protocol: a randomized, blinded, efficacy trial of standard vs. intensive hyperglycemia management in acute stroke.

RATIONALE: Patients with acute ischemic stroke and hyperglycemia have worse outcomes than those without hyperglycemia. Intensive glucose control during acute stroke is feasible and can be accomplished safely but has not been fully assessed for efficacy. AIMS: The Stroke Hyperglycemia Insulin Network Effort trial aims to determine the safety and efficacy of standard vs. intensive glucose control with insulin in hyperglycemic acute ischemic stroke patients. DESIGN: This is a randomized, blinded, multicenter, phase III trial of approximately 1400 hyperglycemic patients who receive either standard sliding scale subcutaneous insulin (blood glucose range 80-179 mg/dL, 4·44-9·93 mmol/L) or continuous intravenous insulin (target blood glucose 80-130 mg/dL, 4·44-7·21 mmol/L) for up to 72 h, starting within 12 h of stroke symptom onset. The acute treatment phase is single blind (for the patients), but the final outcome assessment is double blind. The study is powered to detect a 7% absolute difference in favorable outcome at 90 days. STUDY OUTCOMES: The primary outcome is a baseline severity adjusted 90-day modified Rankin Scale score, defined as 0, 0-1, or 0-2, if the baseline National Institutes of Health Stroke Scale score is 3-7, 8-14, or 15-22, respectively. The primary safety outcome is the rate of severe hypoglycemia (<40 mg/dL, <2·22 mmol/L). DISCUSSION: This trial will provide important novel information about preferred management of acute ischemic stroke patients with hyperglycemia. It will determine the potential benefits and risks of intensive glucose control during acute stroke.

A retrospective cohort study of a nurse-driven computerized insulin infusion program versus a paper-based protocol in critically ill patients.

BACKGROUND: There is variability in the extent of outcome achievement between computerized insulin infusion programs (CIIPs) and paper-based protocols (PBPs). This reported variability may be improved by intensive CIIP training prior to implementation. The objective was to evaluate the impact of a CIIP following intensive nurse training versus a PBP in a critical care setting. METHODS: A retrospective cohort study was performed on patients admitted to a mixed intensive care unit comparing glucose control between the CIIP following intensive training and a PBP. Consecutive patients on each protocol were assessed to obtain glucose concentrations and outcomes. The primary measure was the percentage of blood glucose values within target range (90-130 mg/dL). Patient glucose values were pooled and assessed using the χ(2) test for independence. RESULTS: In total, 61 patients with 5,495 glucose tests were included in the PBP group, and 51 patients with 5,645 glucose tests in the CIIP group. A greater percentage of glucose tests was within target range in the CIIP group (68.4% vs. 36.5%, P<0.001). In the CIIP group, time-to-target (median [interquartile range] 5 [3-8] h vs. 7 [4-20] h, P=0.02) and severe hypoglycemic events were reduced (26 vs. 6, P<0.0001). CONCLUSIONS: The nurse-driven CIIP led to a higher percentage of glucose values within target range, faster achievement of target glucose values, and a reduction in the number of severe hypoglycemic events. This improved outcome achievement compared with previous reports may be associated with intensive user training.

Management of hyperglycemia in acute ischemic stroke.

OPINION STATEMENT: There is considerable clinical evidence that hyperglycemia at the onset of acute ischemic stroke may negatively impact not only acute morbidity but also brain recovery. Establishing hyperglycemia treatment protocols is challenging, given the variation among patients and acute stroke care settings. Relatively few randomized trials have examined glycemic control protocols in this population, and there is not yet any clear evidence that "correcting" hyperglycemia in patients with acute stroke leads to better functional outcomes. Intensification of glucose regimens, using lower glucose targets, leads to more hypoglycemic events, but the immediate and long-term impact of these events on the acutely ischemic brain is unknown. It is reasonable to treat patients with acute ischemic stroke according to the American Diabetes Association inpatient glycemic control guidelines, initiating therapy to achieve glucose targets of 140 to 180 mg/dL if fasting glucose is greater than 140 mg/dL or random glucose is consistently higher than 180 mg/dL. Lower glucose targets (<140 mg/dL) may be appropriate for patients with well-controlled diabetes and those with stress hyperglycemia who were not known to be diabetic before admission, but glucose levels less than 80 mg/dL should be avoided. Patients who present with extreme or persistent hyperglycemia, are critically ill, or who are treated with thrombolytic therapy should be started on an established and standardized intravenous insulin protocol to improve blood glucose control for at least the first 24 to 48 h of hospitalization. They should then be transitioned to a subcutaneous insulin regimen that includes basal long-acting insulin along with correction rapid-acting insulin for glucose that is out of range. Prandial (meal) insulin should be added for patients who are eating; this would preferably be a rapid-acting insulin analogue that can be administered immediately before or after the meal. Caution and close glucose monitoring are necessary, especially for patients prone to hypoglycemia, such as those with type 1 diabetes mellitus or hepatic or renal impairment, or those on complicated feeding regimens.

Facilitating process changes in meal delivery and radiological testing to improve inpatient insulin timing using six sigma method.

BACKGROUND: The objective of this project was to improve the timing of inpatient insulin administration related to meal delivery and the scheduling of radiology tests by Lean Six Sigma method. METHODS: A multidisciplinary hospital team and a Six Sigma team from a pharmaceutical manufacturer collaborated to evaluate food delivery and radiology scheduling processes related to the timing of insulin administration. Key factors leading to problems within each system were addressed to improve the efficiency of each process while improving the timeliness of glucose testing and insulin administration. RESULTS: Standardizing the food delivery schedule and utilizing scorecards to track on-time meal deliveries to the floor enabled nursing to more accurately administer insulin in coordination with the delivery of meals. Increasing communication and restricting the scheduling of inpatient procedures during mealtimes reduced disruptions to insulin administration. Data at 6 months postimplementation demonstrated that the institution met goals for most primary outcome metrics including increasing on-time meal delivery and the proportion of patients taking insulin scheduled for radiology tests during appropriate times. CONCLUSION: By implementing the recommendations identified via Lean Six Sigma, this collaborative effort improved the timing of inpatient insulin administration related to meal delivery and radiology testing.

The nuts and bolts of subcutaneous insulin therapy in non-critical care hospital settings.

In non-critical care settings, patients with hyperglycemia experience increased morbidity and mortality. Despite an increased recognition of the importance of treating inpatient hyperglycemia, many patients are still not adequately controlled. Insulin offers flexibility to address varying glucose levels and therefore is the preferred therapy to achieve recommended targets and manage hyperglycemia. Traditional sliding-scale insulin regimens often ineffectively control blood glucose levels as they are unable to mimic physiologic insulin secretion. Basal-bolus insulin regimens are recognized as a more effective way to correct hyperglycemia in non-critical care settings and a systematic glycemic control program is necessary to address hyperglycemia while minimizing hypoglycemia. Critical components of these programs include addressing barriers to glycemic control, understanding varying needs of different types of patients, and developing standardized subcutaneous insulin orders to achieve target glucose levels. This article provides strategies for using insulin in non-critical care settings to facilitate glycemic control.