Insulin Dose Titration Research Articles

Efficacy and safety of oral basal insulin versus subcutaneous insulin glargine in type 2 diabetes: a randomised, double-blind, phase 2 trial

Oral insulin 338 (I338) is a long-acting, basal insulin analogue formulated in a tablet with the absorption-enhancer sodium caprate. We investigated the efficacy and safety of I338 versus subcutaneous insulin glargine (IGlar) in patients with type 2 diabetes. This was a phase 2, 8-week, randomised, double-blind, double-dummy, active-controlled, parallel trial completed at two research institutes in Germany. Insulin-naive adult patients with type 2 diabetes, inadequately controlled on metformin monotherapy or combined with other oral antidiabetic drugs (HbA1c 7·0-10·0%; BMI 25·0-40·0 kg/m2), were randomly assigned (1:1) to receive once-daily I338 plus subcutaneous placebo (I338 group) or once-daily IGlar plus oral placebo (IGlar group). Randomisation occurred by interactive web response system stratified by baseline treatment with oral antidiabetic drugs. Patients and investigators were masked to treatment assignment. Weekly insulin dose titration aimed to achieve a self-measured fasting plasma glucose (FPG) concentration of 4·4-7·0 mmol/L. The recommended daily starting doses were 2700 nmol I338 or 10 U IGlar, and maximum allowed doses throughout the trial were 16 200 nmol I338 or 60 U IGlar. The primary endpoint was treatment difference in FPG concentration at 8 weeks for all randomly assigned patients receiving at least one dose of trial product (ie, the full analysis set). The trial has been completed and is registered at ClinicalTrials.gov, number NCT02470039. Between June 1, 2015, and Oct 19, 2015, 82 patients were screened for eligibility and 50 patients were randomly assigned to the I338 group (n=25) or the IGlar group (n=25). Mean FPG concentration at baseline was 9·7 (SD 2·8) in the I338 group and 9·1 (1·7) in the IGlar group. Least square mean FPG concentration at 8 weeks was 7·1 mmol/L (95% CI 6·4-7·8) in the I338 group and 6·8 mmol/L (6·5-7·1) in the IGlar group, with no significant treatment difference (0·3 mmol/L [-0·5 to 1·1]; p=0·46). I338 and IGlar were well tolerated by patients. Adverse events were reported in 15 (60%) patients in the I338 group and 17 (68%) patients in the IGlar group. The most common adverse events were diarrhoea (three [12%] patients in each group) and nasopharyngitis (five [20%] in the I338 group and two [8%] in the IGlar group). Most adverse events were graded mild (47 of 68 events), and no severe adverse events were reported. One patient in the IGlar group had a treatment-emergent serious adverse event (urogenital haemorrhage of moderate intensity, assessed by the investigator as unlikely to be related to treatment; the patient recovered). Incidence of hypoglycaemia was low in both groups (n=7 events in the I338 group; n=11 in the IGlar group), with no severe episodes. I338 can safely improve glycaemic control in insulin-naive patients with type 2 diabetes with no evidence of a difference compared with insulin glargine, a widely used subcutaneously administered basal insulin. Further development of this particular oral insulin project was discontinued because I338 doses were high and, therefore, production of the required quantities of I338 for wide public use was deemed not commercially viable. Improvement of technologies involved in the product's development is the focus of ongoing research. Novo Nordisk.

Dose titration model and correlative factors analysis in Chinese patients with type-2 diabetes on basal insulin - results from an Observational Registry of Basal Insulin Treatment study.

This study evaluates an insulin dose titration model and factors that impact insulin dose adjustment in Chinese adults with type-2 diabetes, who receive basal insulin in real-world settings. A total of 19,894 patients from the ORBIT study were included. These patients were divided into four groups, according to the type of insulin dose adjustment: no insulin titration (group A), self-titration (group B), physician-led insulin titration (group C), and combined physician and patient-led insulin titration (group D). Data were collected and compared at baseline and after six months of treatment. A total of 12,865 patients completed the visits and were included in the analysis. Among these patients, 3187 (24.8%), 1971 (15.3%), 5165 (40.1%), and 2542 (19.8%) patients were included in groups A, B, C, and D, respectively. The multivariate logistic regression analysis revealed that the duration of diabetes, body mass index, microvascular complications, inpatient days, HbA1C level, and self-monitoring of blood glucose (SMBG) were positively correlated with insulin titration in group B, C, and D, compared with group A. The number of inpatient days and outpatient visits were positively correlated with dose adjustment for physician-led titration, while this was negatively correlated for self-titration. Self-titration encouraged by physicians and home blood glucose monitoring were positively correlated with self-titration and the combined physician and patient-led titration. High HbA1C level, SMBG, long disease duration, microvascular complications, and the encouragement of physicians while initiating insulin use prompt patients to perform dose adjustments in real-world settings.

Optimizing Basal-Bolus Therapy in T2D—A Randomized Controlled Trial Comparing Bolus Insulin Delivery Using an Insulin Patch vs. an Insulin Pen

Optimizing Basal-Bolus Therapy in T2D—A Randomized Controlled Trial Comparing Bolus Insulin Delivery Using an Insulin Patch vs. an Insulin Pen

Efficacy of a Basal-Plus Regimen

Aim: To find out Efficacy of a basal plus regimen. Objectives: 1. To find out the efficacy of basal plus regime by evaluating the changes in HbA1c at 24 weeks. 2. To find out changes in weight and frequency of hypoglycemia after initiation of the basal plus regime. Method: The study was a prospective analysis of 24 weeks after initiation of basal plus regime. Inclusion criteria: T2DM>5 Years; On 3OAD + basal insulin, HbA1c- 7.5-8.5%. Exclusion Criteria: critically ill patients, acute infection, pregnant, T1D. All patients matching the inclusion criteria were analyzed on the basis of SMBG chart to find out their highest glycemic excursion of post prandial and fasting readings. Based on the diet recall and sugar reading charts these patients were initiated on bolus insulin with the largest meal of the day where their post prandial corresponded to the highest reading. They were educated on proper insulin injection techniques and SMBG and asked to follow-up with their sugar readings using telemedicine application every day. Result: We studied 220 patients (F=124 M=96) with HbA1c at baseline 7.5-8.5% (avg-8.0). After addition of bolus insulin at 12 weeks target HbA1c <7% was achieved in 55.9% (n=123) patients with minor dose titrations. Average HbA1c at 12 Weeks was 7.3%. At 24Weeks target HbA1c was achieved in 88.18% (n=194) of patients after uptitration of bolus dose. Average HbA1c at 24Weeks was 6.9%. 5 patients experienced severe hypoglycemic episode. Cases of 15 average mild to moderate hypoglycemic episodes were reported. Regular SMBG and follow-up of the patients through telemedicine applications is continued for insulin dose titration. Fasting sugar target of below 110 mg/dl was achieved through titration of basal insulin in all 220 patients at the end of 12 weeks. Post prandial glycemic readings at the end of 12 weeks were achieved below 160 mg/dl in 167 patients and at 24 weeks in 198 patients. Conclusion: After failure of OADS and basal insulin a basal plus regime with addition of 1 bolus insulin with the largest meal of the day helped achieve the target HbA1c of <7% effectively. Disclosure B.D.J. Saboo: None. D. Hasnani: None. H. Chandarana: None. S. Bhandari: None. S. Joshi: None. J. Kesavadev: Advisory Panel; Self; Novo Nordisk India Private Limited. Speaker's Bureau; Self; Novo Nordisk India Private Limited. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; MSD. Speaker's Bureau; Self; MSD. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. A. Maheshwari: None. H. Thacker: Research Support; Self; Wockhardt LTD.

Insulin glargine 300 U/ml in type 2 diabetes mellitus patients: results of the EDITION program (review)

Unmet medical needs in basal insulin therapy include late initiation of therapy, hypoglycemia, and low patient compliance. Introduction of new basal insulin may cater to these unmet medical needs.
 New insulin glargine 300 U/mL (Gla-300) (Toujeo) is a long-acting basal insulin with a more even and prolonged PK/PD profile compared to those of insulin glargine 100 (Lantus). The glucose infusion rate profiles and insulin concentration of Gla-300 were more constant and more evenly distributed over 24 h compared to those of glargine 100 U/mL. Stable blood glucose control (≤ 5.5 mmol/L) was maintained approximately 5 h longer with glargine 300 U/mL compared to glargine 100 U/mL. The difference in PK/PD profiles of glargine 300 U/mL and glargine 100 U/mL may be a key to explanation of the Toujeo® clinical features demonstrated in the EDITION program.
 This review discusses the EDITION clinical program results in type 2 diabetes mellitus (T2MD) patients, except EDITION JP2: on previous basal-bolus therapy (EDITION 1, n=807), previous basal insulin in combination with oral anti-diabetic drug (EDITION 2, n=811), and insulin naive patients (oral anti-diabetic drug excl. SU) (EDITION 3, n=878). The EDITION program was aimed to assess the efficacy and safety of Gla-300 compared to those of glargine 100 U/mL. EDITION programs were multicenter, 1:1 randomized, open-label, parallel group, phase III, and non-inferiority studies, with similar designs and endpoints. The primary endpoint was the non-inferiority of Gla-300 vs glargine 100 U/mL, which was estimated as a HbA1c reduction at 6 months. The main secondary endpoint was the percentage of participants with one or more nocturnal confirmed (≤3.9 mmol/L) or severe hypoglycemic events from week 9 to month 6 of treatment. Patients were randomized to glargine 300 U/mL or glargine 100 U/mL once a day, with dose titration seeking fasting plasma glucose of 4.4—5.6 mmol/L.
 Non-inferiority of glargine 300 U/mL in the HbA1C reduction vs glargine 100 U/mL was confirmed in EDITION 1, EDITION 2, and EDITION 3 studies. According to the results of a pool analysis of these three trials, annualized rates of confirmed (≤3.9 mmol/L) or severe hypoglycemia were lower with glargine 300 U/mL than with glargine 100 U/mL during the night (31% difference in the rate ratio over 6 months, p=0.0002) and at any time (24 h, 14% difference, p=0.0116). Severe hypoglycemia at any time was rare (glargine 300 U/mL: 2.3%; glargine 100 U/mL: 2.6%). Weight gain was low (<1 kg) in both groups, with the gain being less with glargine 300 U/ml [LS mean difference —0.28 kg (95% CI –0.55 to –0.01); p=0.039]. Both treatments were well tolerated, having similar rates of adverse events.
 In conclusion, glargine 300 U/mL was characterized by the non-inferior efficacy compared to glargine 100 U/mL, a better safety profile (reduced hypoglycemia), and lower weight gain. These advantages may allow for more active insulin dose titration in real clinical practice, contribute to better-sustained glycemic control and patient compliance, and, consequently, improve the prognosis and clinical outcome.

An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial

BackgroundA Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity and stability of an information and communication technology (ICT)-based centralized clinical trial monitoring system.MethodsThis is a 24-week, open-label, randomized, multi-center trial. There are three follow-up measures: baseline, post-intervention at week 12, and at week 24. Subjects diagnosed with type 1 DM, type 2 DM, and/or post-transplant DM who initiate basal insulin or intensify their insulin regimen to a basal-bolus regimen are included. After education on insulin dose titration and prevention for hypoglycemia and a 1-week acclimation period, subjects are randomized in a 1:1 ratio to either an ICT-based intervention group or a conventional intervention group. Subjects in the conventional intervention group will save and send their health information to the server via a PHR application, whereas those in ICT-based intervention group will receive additional algorithm-based feedback messages. The health information includes level of blood glucose, insulin dose, details on hypoglycemia, food diary, and step count. The primary outcome will be the proportion of patients who reach an optimal insulin dose within 12 weeks of study enrollment, without severe hypoglycemia or unscheduled clinic visits.DiscussionThis clinical trial will reveal whether insulin dose adjustment based on a smartphone PHR application can facilitate the optimization of insulin doses in patients with DM. In addition, the process evaluation will provide information about the validity and stability of the ICT-based centralized clinical trial monitoring system in this research field.Trial registrationClinicaltrials.gov NCT 03112343. Registered on 12 April 2017.

Practical use of insulin in diabetes mellitus

Insulin therapy is the cornerstone of treatment in patients with type 1 diabetes mellitus (DM) and advanced type 2 DM. Over the years, insulin treatment has advanced from animal insulin to recombinant insulin with more efficiency and fewer side effects and from short-acting conventional insulin to ultrashort and long-acting insulin analogs to mimic various phases of physiological insulin secretion. Various insulin delivery systems from conventional subcutaneous insulin injection using insulin syringe to pen device, subcutaneous insulin infusion pumps, and inhaled insulin to artificial pancreas are now available. Proper insulin injecting techniques and patient education on self-monitoring of blood glucose and insulin dose titration are of utmost importance for effective insulin therapy.

Mobile Insulin Dosing System Formative Study

Background: Titrating long acting insulin is a significant challenge for physicians and patients. The most advanced method is a paper titration form, which is often error prone, especially if the patient has low numeracy skills. The limitations of the paper titration form can be mitigated by using a smartphone-based, mobile insulin dosing system (MIDS). Reducing barriers to insulin therapy, including dosing and titration, can empower clinicians and patients to achieve glycemic control. Objective: The objective of this human factor formative study was to obtain feedback, from healthcare providers (HCPs) and insulin-treated patients with type 2 diabetes, on a prototype of a MIDS. MIDS consists of an easy to setup patient instruction form (PIF), configured by HCPs, and easy to understand mobile prompts and reminders for patients to assist with self-adjustment of their insulin dose. The MIDS will use patients’ fasting blood glucose (BG) readings, synced from their glucose meter using Glooko, for insulin dose calculations. Clinicians can monitor patients’ progress via Glooko’s Web-based user interface. Methods: A total of 15 HCPs, including 7 certified diabetes educators, 2 primary care physicians, 1 pharmacist, 1 medical informatics leader, and 4 endocrinologists, as well as 4 patients with type 2 diabetes and 1 patient with hemochromatotic diabetes, on insulin therapy, were interviewed. The structured one-on-one interviews lasted 60 minutes and were conducted in person or virtually. During the structured interview, a discussion guide was used to pose questions in a specific order. The order of questions was determined by the order of screenshots in the Web-based patient instruction form and mobile messages received by patients. Probing questions were asked to evaluate the reasons behind the responses. Results: All of the HCPs interviewed stated that the ability to share an insulin titration template with colleagues and a mobile insulin dosing for patients were valuable. Other findings include the following: 80% of HCPs use age and weight to determine starting insulin dose; about 70% of HCPs would set up reminders in the application to instruct their patients to test fasting BG and administer insulin at specific times; and all HCPs wanted patients to be alerted to contact their physician if their fasting BG reading was beyond the provider-set hypoglycemic or hyperglycemic threshold. Findings from patient interviews include the following: 75% of the participants said that they would not get reminder fatigue but wanted the ability to edit or dismiss the reminders; 80% of the participants wanted the ability to pause the MIDS program and let the program provide them prompts and reminders even when they were within their target fasting BG range; and all of the patients stated that being able to see their dose adjustment history was helpful. Conclusions: Key design recommendations emerged from this formative evaluation. Based on feedback received from the HCPs and patients, the reminders setting will be refined. Results led to improvements and optimization of the MIDS and supports further development of MIDS as a mobile system that helps with basal insulin dose titration was positively received by providers and patients. [iproc 2016;2(1):e26]

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Introduction: Subcutaneous insulin may be utilized for the treatment of hyperglycemia in the intensive care unit (ICU) in selected patients; however, available evidence does not provide an optimal glucose management strategy to guide subcutaneous insulin product selection and dose titration. Methods: This was a prospective, open-label, randomized study. Patients were eligible for inclusion if they required initiation of basal insulin therapy in the medical ICU. They were randomized by bed number to receive either insulin glargine or NPH insulin. All other decisions regarding insulin management, including insulin dose titration, were made according to standard care. The primary outcome was hyperglycemic events, defined as blood glucose greater than 180 mg/dL. Secondary outcomes included hypoglycemia, defined as blood glucose less than 70 mg/dL; ICU length of stay (LOS); hospital LOS; and hospital mortality. Glucose data was clustered by patient and analyzed using a generalized estimating equation procedure. Results: From October 2012 to March 2013, a total of 55 patients were enrolled in the study. The total daily basal insulin dose was similar between the NPH insulin group (59 ± 47 units) and the insulin glargine group (72 ± 51 units, p = 0.34). Patients in the NPH insulin group were at a significantly lower risk for hyperglycemia when compared to patients in the insulin glargine group (RR 0.65, 95% CI 0.44 - 0.95). There was no difference between the two groups in the risk of hypoglycemia (RR 1.56, 95% CI 0.29 - 8.51). There were no significant differences found between the groups regarding ICU LOS, hospital LOS, or hospital mortality. Conclusions: NPH insulin was more effective than insulin glargine for reducing hyperglycemia in critically ill medical patients. Furthermore, there were no differences found in terms of the risk of hypoglycemia, ICU or hospital LOS, or hospital mortality.

Treat-to-target comparison between once daily biphasic insulin aspart 30 and insulin glargine in Chinese and Japanese insulin-naïve subjects with type 2 diabetes

Objective:To investigate whether once daily biphasic insulin aspart 30 (BIAsp 30) is noninferior to once daily insulin glargine (IGlar) among Chinese and Japanese insulin-naïve subjects with type 2 diabetes mellitus (T2DM).Research design and methods:This was a 24 week treat-to-target trial (NCT01123980) that included patients with T2DM who were poorly controlled on a combination of metformin and insulin secretagogue (or with a maximum of one more OAD) for 6 months. Patients were randomized to once daily BIAsp 30 or once daily IGlar and their secretagogue standardized to glimepiride 4 mg/day, metformin to 1500 or 2500 mg/day before randomization.Results:At Week 24, mean change from baseline in HbA1c was −0.78 ± 0.88% (mean ± SD) and −0.65 ± 0.92% (−8.49 ± 9.65 and −7.08 ± 10.1 mmol/mol) for the BIAsp 30 (n = 261) and IGlar (n = 260) groups, respectively. The estimated between-group difference (BIAsp 30 vs IGlar) in HbA1c change was −0.12% (95% CI: −0.25, 0.02) (−1.28 mmol/mol [95% CI: −2.75, 0.19]), thus treatment with BIAsp 30 was noninferior to IGlar with respect to HbA1c (non-inferiority margin 0.4%). Although reduction in mean 9-point self-measured plasma glucose (SMPG) profile was comparable between the two groups, BIAsp 30 showed significantly lower PG levels at three time points post-dinner and a higher PG level before dinner compared to the IGlar group (all p < 0.05). Comparable number of subjects reported hypoglycemic events (155 [59.4%] for BIAsp 30, 148 [56.9%] for IGlar).Conclusions:BIAsp 30 once daily showed similar HbA1c reduction and a similar safety profile to IGlar when used in insulin-naïve Chinese and Japanese patients on metformin and a sulfonylurea. Moreover, it provided a better coverage of post-dinner glycemic control needs than those who received IGlar. The open-label design and insufficient insulin dose titration were the main limitations of the study.Trial registration: ClinicalTrials.gov identifier: NCT01123980.

Glycemia management in critical care patients.

Over the last decade, the approach to clinical management of blood glucose concentration (BGC) in critical care patients has dramatically changed. In this editorial, the risks related to hypo, hyperglycemia and high BGC variability, optimal BGC target range and BGC monitoring devices for patients in the intensive care unit (ICU) will be discussed. Hypoglycemia has an increased risk of death, even after the occurrence of a single episode of mild hypoglycemia (BGC < 80 mg/dL), and it is also associated with an increase in the ICU length of stay, the major determinant of ICU costs. Hyperglycemia (with a threshold value of 180 mg/dL) is associated with an increased risk of death, longer length of stay and higher infective morbidity in ICU patients. In ICU patients, insulin infusion aimed at maintaining BGC within a 140-180 mg/dL target range (NICE-SUGAR protocol) is considered to be the state-of-the-art. Recent evidence suggests that a lower BGC target range (129-145 mg/dL) is safe and associated with lower mortality. In trauma patients without traumatic brain injury, tight BGC (target < 110 mg/dL) might be associated with lower mortality. Safe BGC targeting and estimation of optimal insulin dose titration should include an adequate nutrition protocol, the length of insulin infusion and the change in insulin sensitivity over time. Continuous glucose monitoring devices that provide accurate measurement can contribute to minimizing the risk of hypoglycemia and improve insulin titration. In conclusion, in ICU patients, safe and effective glycemia management is based on accurate glycemia monitoring and achievement of the optimal BGC target range by using insulin titration, along with an adequate nutritional protocol.

Hypoglycemia in patients with type 2 diabetes using concomitant exenatide BID and long-acting insulin therapy

Objective:The objective of this study was to examine the frequency of hypoglycemia among patients with type 2 diabetes who had concomitantly used exenatide BID (exenatide) and long-acting insulin and continued this combination vs those who continued long-acting insulin alone.Methods:Retrospective analyses, using a large managed care database, were used to estimate the frequency of hypoglycemia (episodes/patient/6 months) for patients who concomitantly used exenatide and long-acting insulin during a 6-month follow-up period.Results:From among 2082 patients on concomitant exenatide and long-acting insulin, those who continued this combination (n = 472) had a lower frequency of hypoglycemia compared to those who remained on long-acting insulin alone (n = 312) (0.03 ± 1.9 vs 0.10 ± 1.01 [episodes/patient/6 months]; p < 0.0001).Limitations:Only hypoglycemia that required medical intervention (coded for hypoglycemia) was captured. The study could not evaluate any association between insulin dose titration and hypoglycemia or examine other outcomes such as HbA1c, weight, and body mass index, due to lack of data availability.Conclusions:Patients who concomitantly used exenatide BID and long-acting insulin experienced a lower rate of hypoglycemia.

Comment on: Nauck MA, Duran S, Kim D et al (2007) A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 50:259–267

To the Editor: In their paper published in Diabetologia, Nauck and colleagues suggest that exenatide resulted in reductions in HbA1c and low rates of hypoglycaemia similar to those observed with biphasic insulin aspart (30% fastacting insulin aspart), though with marked differences in body weight trajectory (in favour of exenatide) and withdrawal rates (in favour of biphasic insulin aspart) [1]. However, the study is subject to serious shortcomings. A fair comparison would have optimised both regimens; this appears to have been done for exenatide, as 80% of participants eventually received 10 μg daily, in line with tolerance of this dose in earlier trials [2, 3]. However, insulin regimens, to a much greater extent than oral agents or exenatide, require appropriate insulin dose titration to achieve optimal blood glucose control. In this study, insulin dose adjustment was simply left to the investigator. It is not clear from the paper what intensity of follow-up, selfmonitoring, or dose adjustment to what target occurred, but at 52 weeks the premix insulin dose was only 24 U/day, well below doses used in recent studies [4–8], and below doses normally encountered in clinical practice. This appeared not to be the result of hypoglycaemia in this particular group of patients—the reported hypoglycaemia rate was as low with insulin as with the glucagon-like peptide-1 mimetic. The result of this is that the blood glucose control achieved was relatively poor in the insulin-treated group (a fall of 0.9% in HbA1c from a baseline of 8.6%) when compared with nearly all recently published treat-to-target studies with insulin therapy in people with type 2 diabetes [4–8]. In these, final HbA1c is typically <7.0% (achieved by 68% of participants in the INITIATE study [5], and eventually by 77% of participants in the 1-2-3 study, where a third premix injection was an option) [6]. The LanMet study achieved an HbA1c of 7.1%, but this was from baseline levels of 9.1% [8]. A similar problem bedevilled a previously published exenatide comparison with insulin, in which a change of −1.1% from a baseline HbA1c level of 8.3% was achieved with insulin glargine [3]; in the original treat-to-target study, Riddle and colleagues achieved a 45% greater reduction in HbA1c, from 8.6% at baseline to 7.0% [4]. Similar or better results were achieved with insulin detemir [7]. Again, there is a major difference in insulin dose: 47 U/day in the Riddle study vs just 25 U/day in the exenatide–glargine comparison study [3, 4]. The issue of appropriate comparators, and appropriate use of comparators, is critical to clinical trial designs of this type. In this study the pharmaceutical sponsors chose to use a competitor’s insulin preparation as comparator to exenatide, when they have a very similar product on the market themselves. Was this an informed choice based on the expectation of rather poor results as a result of the study design?

Reliability of point-of-care testing for glucose measurement in critically ill adults*

Glycemic control is increasingly being recognized as a priority in the treatment of critically ill patients. Titration and monitoring of insulin infusions involve frequent blood glucose measurement to achieve target glucose ranges and prevent adverse events related to hypoglycemia. Therefore, it is imperative that bedside glucose testing methods be safe and accurate. To determine the accuracy and clinical impact of three common methods of bedside point-of-care testing for glucose measurements in critically ill patients receiving insulin infusions. Prospective observational study. A 21-bed mixed medical/surgical intensive care unit of a tertiary care teaching hospital. Thirty consecutive critically ill patients who were vasopressor-dependent (n = 10), had significant peripheral edema (n = 10), or were admitted following major surgery (n = 10). Findings from three different methods of glucose measurement were compared with central laboratory measurements: (1) glucose meter analysis of capillary blood (fingerstick); (2) glucose meter analysis of arterial blood; and (3) blood gas/chemistry analysis of arterial blood. Patients were enrolled for a maximum of 3 days and had a maximum of nine sets of measurements determined during this time. Clinical agreement with the central laboratory was significantly better with arterial blood analysis (69.9% and 76.5% for glucose meter and blood gas/chemistry analysis, respectively) than with capillary blood analysis (56.8%; p = .039 and .001, respectively). During hypoglycemia, clinical agreement was only 26.3% with capillary blood analysis and 55.6% and 64.9% for glucose meter and blood gas/chemistry analysis of arterial blood (p = .010 and <.001, respectively). Glucose meter analysis of both arterial and capillary blood tended to provide higher glucose values, whereas blood gas/chemistry analysis of arterial blood tended to yield lower glucose values. The magnitude of the differences in the glucose values offered by the four different methods of glucose measurement led to frequent clinical disagreements regarding insulin dose titration in the context of an insulin infusion protocol for aggressive glucose control.