Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.

Dasiglucagon, a next-generation glucagon analogue, for treatment of severe hypoglycaemia via an autoinjector device: Results of a phase 3, randomized, double-blind trial.

AIM: To confirm the efficacy and safety of dasiglucagon when administered via an autoinjector device. MATERIALS AND METHODS: In this double-blind trial, 45 participants with type 1 diabetes were randomized 3:1 to receive a single subcutaneous dose of dasiglucagon 0.6 mg or placebo following controlled induction of hypoglycaemia. The primary endpoint was time to plasma glucose recovery, defined as a plasma glucose increase of 20 mg/dL or higher from baseline without rescue intravenous glucose. RESULTS: Median (95% CI) observed time to recovery was 10.0 (8.0; 12.0) minutes for dasiglucagon and 35.0 (20.0; -) minutes for placebo (P < .001). Plasma glucose recovery was achieved within 15 minutes by 88% of participants receiving dasiglucagon versus none receiving placebo (P < .01). Site of injection (buttock or deltoid) was not shown to have any effect on time to recovery (P = .84). No serious adverse events occurred. As expected for glucagon treatment, nausea and vomiting were common adverse events in dasiglucagon-treated participants. CONCLUSIONS: Dasiglucagon provided rapid reversal of hypoglycaemia in adults with type 1 diabetes. Dasiglucagon administration was well tolerated. The aqueous formulation of dasiglucagon in a ready-to-use autoinjector device that can be carried at room temperature may provide a reliable treatment for severe hypoglycaemia.

Long-Term Efficacy and Safety of Ultra Rapid Lispro (URLi) in Adults with Type 1 Diabetes: The PRONTO-T1D Extension.

INTRODUCTION: The PRONTO-T1D study, which evaluated the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes (T1D), met the primary endpoint of noninferiority of HbA1c change from baseline compared to lispro at 26 weeks. We present results of an additional 26-week treatment phase evaluating long-term efficacy and safety of URLi. METHODS: In this phase 3, treat-to-target study, subjects were randomized to double-blind mealtime URLi, lispro, or open-label postmeal URLi with insulin degludec or glargine for 26 weeks. Subjects in the double-blind URLi (n = 451) and lispro (n = 442) groups continued for another 26 weeks to assess long-term efficacy and safety. RESULTS: HbA1c increased marginally during the long-term maintenance period (week 26-52) in both groups to 7.47% (URLi) and 7.54% (lispro). At week 52, there were no statistically significant treatment differences in change from baseline HbA1c with a least-squares mean treatment difference (95% confidence interval) of - 0.06% (- 0.16, 0.03). Proportions of patients with HbA1c < 7% at week 52 were similar (URLi, 26.8%; lispro, 24.5%). Self-monitored blood glucose (SMBG) showed that 1-h (9.23 versus 10.14 mmol/L) and 2-h (8.40 versus 9.53 mmol/L) postmeal daily mean glucose was statistically significantly (p < 0.001) lower with URLi than lispro. The rate and incidence of severe, documented, and postprandial hypoglycemia (< 54 mg/dl [3.0 mmol/L]) were similar between treatments, but URLi demonstrated a 31% lower rate in the period more than 4 h after meals, (p = 0.023). Injection site reactions were reported by 3.3% of patients on URLi and 0.9% on lispro. The incidence of treatment-emergent adverse events was similar between treatments. CONCLUSION: Overall glycemic control and improved postprandial glucose via SMBG were maintained after 52 weeks with URLi versus lispro, suggesting that the efficacy of URLi is preserved during long-term treatment in patients with T1D. No long-term safety issues were identified with URLi. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03214367.

Accuracy and User Performance of a New Blood Glucose Monitoring System.

INTRODUCTION: Self-monitoring of blood glucose (BG) is important in diabetes management, allowing people with diabetes (PWD) to assess responses to diabetes therapy and to inform if they are attaining their glycemic targets. This study assessed the accuracy and user performance (UP) of a new blood glucose monitoring system (BGMS), CONTOUR®PLUS ELITE, according to International Organization for Standardization (ISO) 15197:2013 criteria and also more stringent criteria. METHODS: In laboratory Study 1, capillary fingertip blood samples from 100 PWD were evaluated using the new BGMS. In clinical Study 2, 130 PWD had Yellow Springs Instrument (YSI) analyzer reference measurements against subject-obtained fingertip and palm blood, and trial staff-obtained venous blood. The new BGMS was tested with test strips from three different lots. A UP questionnaire assessed ease of use. RESULTS: Study 1: 100% of combined accuracy results fulfilled ISO criteria (±15 mg/dL at BG <100 mg/dL; ±15% at BG ≥100 mg/dL); 99.8% fulfilled more stringent criteria (±10 mg/dL at BG <100 mg/dL; ±10% at BG ≥100 mg/dL). Error grid analysis showed that 100% of results were within zone A. Study 2: >98% of subject- and 100% of trial staff-obtained performance results met ISO criteria. Most subjects (>96%) found the BGMS easy to use. CONCLUSION: The new BGMS exceeded minimum ISO 15197:2013-specified standards for both accuracy and UP criteria, along with the more stringent accuracy criteria. These data show that this new BGMS can be a useful tool in managing glycemic control for PWD.

Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26-week PRONTO-T1D study.

AIMS: To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes in a 26-week, treat-to-target, phase 3 trial. MATERIALS AND METHODS: After an 8-week lead-in to optimize basal insulin glargine or degludec, patients were randomized to double-blind mealtime URLi (n = 451) or lispro (n = 442), or open-label post-meal URLi (n = 329). The primary endpoint was change from baseline glycated haemoglobin (HbA1c) to 26 weeks (non-inferiority margin 0.4%), with multiplicity-adjusted objectives for postprandial glucose (PPG) excursions after a meal test. RESULTS: Both mealtime and post-meal URLi demonstrated non-inferiority to lispro for HbA1c: estimated treatment difference (ETD) for mealtime URLi -0.08% [95% confidence interval (CI) -0.16, 0.00] and for post-meal URLi +0.13% (95% CI 0.04, 0.22), with a significantly higher endpoint HbA1c for post-meal URLi versus lispro (P = 0.003). Mealtime URLi was superior to lispro in reducing 1- and 2-hour PPG excursions during the meal test: ETD -1.55 mmol/L (95% CI -1.96, -1.14) at 1 hour and - 1.73 mmol/L (95% CI -2.28, -1.18) at 2 hours (both P < 0.001). The rate and incidence of severe, documented and postprandial hypoglycaemia (<3.0 mmol/L) was similar between treatments, but mealtime URLi demonstrated a 37% lower rate in the period >4 hours after meals (P = 0.013). Injection site reactions were reported by 2.9% of patients on mealtime URLi, 2.4% on post-meal URLi, and 0.2% on lispro. Overall, the incidence of treatment-emergent adverse events was similar between treatments. CONCLUSIONS: The results showed that URLi provided good glycaemic control, with non-inferiority to lispro confirmed for both mealtime and post-meal URLi, while superior PPG control was demonstrated with mealtime dosing.

Fingerstick Precision and Total Error of a Point-of-Care HbA1c Test.

BACKGROUND: Point-of-care (POC) HbA1c tests hold the promise of reducing the rates of undiagnosed diabetes, provided they exhibit acceptable analytical performance. The precision and total error of the POC (Afinion™ HbA1c Dx) test were investigated using whole blood samples obtained by fingerstick and venipuncture. METHODS: Fingerstick samples spanning the assay range were collected from 61 subjects at three representative POC sites. At each site, six fingerstick samples were obtained from each subject and tested on the POC test across two (Afinion AS100) instruments. Repeatability, between-operator, and between-instrument components of variance were calculated using analysis of variance (ANOVA). Four venous samples (low, threshold, medium, and high HbA1c) were measured in duplicate across three instruments using three reagent lots, twice per day over 20-days. Repeatability, between-run, between-day, between-lot, and between-instrument components of variance were calculated. These fingerstick and venous blood results, combined with estimates of imprecision and bias from a prior investigation, allowed for the calculation of the total coefficient of variation (CV) and total error of the POC test using fingerstick and venous whole blood samples. RESULTS: The total imprecision ranged from 1.30% to 2.03% CV using fingerstick samples and from 1.31% to 1.64% CV using venous samples. The total error ranged from 2.87% to 4.75% using fingerstick samples and from 2.93% to 3.80% using venous samples. CONCLUSIONS: The POC test evaluated here is precise across its measuring range using both fingerstick and venous whole blood. The calculated total error of the test is well under the accepted quality requirement of ≤6%.

A Prospective Multicenter Evaluation of the Accuracy and Safety of an Implanted Continuous Glucose Sensor: The PRECISION Study.

Background: A prior study (PRECISE II) demonstrated that an implantable continuous glucose monitoring (CGM) system (Eversense® CGM System) provided accurate glucose readings through the 90-day sensor life with a favorable safety profile in participants with type 1 or type 2 diabetes (T1D, T2D). This study was performed to further characterize the accuracy of the system. Methods: PRECISION was a prospective multicenter study that evaluated the accuracy and safety of Eversense among adults with T1D or T2D through 90 days (NCT02647905). Accuracy measures included percentage system agreement and mean absolute relative difference (MARD) between Eversense and Yellow Springs Instrument reference measurements from 40 to 400 mg/dL. The primary safety endpoint was incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days. An updated glucose calculation algorithm was also applied to the sensor data from the PRECISE II study to evaluate consistency of accuracy results. Results: Thirty-five participants received the CGM system. Eighty-five percent of CGM values were within 15/15% of reference and the MARD value against reference was 9.6% (95% confidence interval [CI]: 8.9-10.4). All sensors were functional through day 90. No device- or procedure-related SAEs occurred. Application of the updated algorithm to PRECISE II sensor data resulted in 87% of readings within 15/15% of reference and an MARD value against reference of 8.5% (95% CI: 8.0%-9.1%). Conclusions: PRECISION corroborated prior accuracy and safety findings of the Eversense CGM System through the 90-day sensor life. The updated algorithm improved accuracy of measurements in PRECISE II.

Improved Postprandial Glucose with Inhaled Technosphere Insulin Compared with Insulin Aspart in Patients with Type 1 Diabetes on Multiple Daily Injections: The STAT Study.

BACKGROUND: The majority of therapies have generally targeted fasting glucose control, and current mealtime insulin therapies have longer time action profiles than that of endogenously secreted insulin. The primary purpose of this study was to assess both glucose time-in-range (TIR: 70-180 mg/dL) and postprandial glucose excursions (PPGE) in 1-4 h using a real-time continuous glucose monitor (CGM) with Technosphere insulin (TI) versus insulin aspart in patients with type 1 diabetes (T1DM) on multiple daily injections (MDI). RESEARCH DESIGN AND METHODS: This pilot, investigator-led, collaborative, open-label, multicenter, clinical research trial enrolled 60 patients with T1DM with HbA1c levels ≥6.5% and ≤10%. Individuals were randomized to treatment with titrated TI (n = 26) or titrated insulin aspart (n = 34), stratified by baseline HbA1c levels (≤8% or >8%). All were required to wear a real-time CGM throughout the trial. All patients in the TI group were advised to take supplemental inhalations at 1 and 2 h after meals if indicated based on postprandial glucose (PPG) values. The coprimary outcomes were assessed both in the full intent-to-treat population and in those individuals randomized to TI who were compliant with supplemental doses ≥90% of the time (n = 15). The CGM data were analyzed using linear regression models. RESULTS: Overall, those treated with TI versus aspart achieved comparable TIR, but less time spent in hypoglycemia (<60 and <50 mg/dL, both P < 0.05). In the TI-compliant group (n = 15), TIR was significantly greater (62.5% ± 2.6% vs. 53.8% ± 1.7%, P = 0.009) and time in hyperglycemia >180 mg/dL was lower (34.2% ± 2.7% vs. 41.0% ± 1.7%, P = 0.045) as compared with the aspart group. PPG was also significantly lower in the TI cohort at 60 and 90 min postmeal, and PPGE were lower in the TI-compliant group as compared with the aspart group over 1-4-h postmeal (P < 0.05). In addition, there was weight gain in the aspart group compared with weight loss in the TI group (P = 0.006) despite higher prandial TI insulin dose. CONCLUSIONS: We conclude that using TI appropriately at mealtimes with supplemental dosing improves prandial glucose (TIR and 1-4 h) control without any increase in time in hypoglycemia or weight gain in patients with T1DM on MDI. The study results support a larger study using a treat-to-target design to confirm these findings. Clinical trial reg. no. NCT03143816, clinicaltrials.gov .

A Prospective Multicenter Evaluation of the Accuracy of a Novel Implanted Continuous Glucose Sensor: PRECISE II.

BACKGROUND: Persistent use of real-time continuous glucose monitoring (CGM) improves diabetes control in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D). METHODS: PRECISE II was a nonrandomized, blinded, prospective, single-arm, multicenter study that evaluated the accuracy and safety of the implantable Eversense CGM system among adult participants with T1D and T2D (NCT02647905). The primary endpoint was the mean absolute relative difference (MARD) between paired Eversense and Yellow Springs Instrument (YSI) reference measurements through 90 days postinsertion for reference glucose values from 40 to 400 mg/dL. Additional endpoints included Clarke Error Grid analysis and sensor longevity. The primary safety endpoint was the incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days postinsertion. RESULTS: Ninety participants received the CGM system. The overall MARD value against reference glucose values was 8.8% (95% confidence interval: 8.1%-9.3%), which was significantly lower than the prespecified 20% performance goal for accuracy (P < 0.0001). Ninety-three percent of CGM values were within 20/20% of reference values over the total glucose range of 40-400 mg/dL. Clarke Error Grid analysis showed 99.3% of samples in the clinically acceptable error zones A (92.8%) and B (6.5%). Ninety-one percent of sensors were functional through day 90. One related SAE (1.1%) occurred during the study for removal of a sensor. CONCLUSIONS: The PRECISE II trial demonstrated that the Eversense CGM system provided accurate glucose readings through the intended 90-day sensor life with a favorable safety profile.

Fundamental Importance of Reference Glucose Analyzer Accuracy for Evaluating the Performance of Blood Glucose Monitoring Systems (BGMSs).

BACKGROUND: As blood glucose monitoring system (BGMS) accuracy is based on comparison of BGMS and laboratory reference glucose analyzer results, reference instrument accuracy is important to discriminate small differences between BGMS and reference glucose analyzer results. Here, we demonstrate the important role of reference glucose analyzer accuracy in BGMS accuracy evaluations. METHODS: Two clinical studies assessed the performance of a new BGMS, using different reference instrument procedures. BGMS and YSI analyzer results were compared for fingertip blood that was obtained by untrained subjects' self-testing and study staff testing, respectively. YSI analyzer accuracy was monitored using traceable serum controls. RESULTS: In study 1 (N = 136), 94.1% of BGMS results were within International Organization for Standardization (ISO) 15197:2013 accuracy criteria; YSI analyzer serum control results showed a negative bias (-0.64% to -2.48%) at the first site and a positive bias (3.36% to 6.91%) at the other site. In study 2 (N = 329), 97.8% of BGMS results were within accuracy criteria; serum controls showed minimal bias (<0.92%) at both sites. CONCLUSIONS: These findings suggest that the ability to demonstrate that a BGMS meets accuracy guidelines is influenced by reference instrument accuracy.

The Performance and Usability of a Factory-Calibrated Flash Glucose Monitoring System.

INTRODUCTION: The purpose of the study was to evaluate the performance and usability of the FreeStyle(®) Libre™ Flash glucose monitoring system (Abbott Diabetes Care, Alameda, CA) for interstitial glucose results compared with capillary blood glucose results. MATERIALS AND METHODS: Seventy-two study participants with type 1 or type 2 diabetes were enrolled by four U.S. clinical sites. A sensor was inserted on the back of each upper arm for up to 14 days. Three factory-only calibrated sensor lots were used in the study. Sensor glucose measurements were compared with capillary blood glucose (BG) results (approximately eight per day) obtained using the BG meter built into the reader (BG reference) and with the YSI analyzer (Yellow Springs Instrument, Yellow Springs, OH) reference tests at three clinic visits (32 samples per visit). Sensor readings were masked to the participants. RESULTS: The accuracy of the results was demonstrated against capillary BG reference values, with 86.7% of sensor results within Consensus Error Grid Zone A. The percentage of readings within Consensus Error Grid Zone A on Days 2, 7, and 14 was 88.4%, 89.2%, and 85.2%, respectively. The overall mean absolute relative difference was 11.4%. The mean lag time between sensor and YSI reference values was 4.5±4.8 min. Sensor accuracy was not affected by factors such as body mass index, age, type of diabetes, clinical site, insulin administration, or hemoglobin A1c. CONCLUSIONS: Interstitial glucose measurements with the FreeStyle Libre system were found to be accurate compared with capillary BG reference values, with accuracy remaining stable over 14 days of wear and unaffected by patient characteristics.

Accuracy and user performance evaluation of the Contour(®) Next Link 2.4 blood glucose monitoring system.

BACKGROUND: The Contour(®) Next Link 2.4 blood glucose monitoring system (BGMS), which communicates wirelessly exclusively with a Medtronic insulin pump, was assessed in 2 separate studies. METHODS: In the laboratory study (N=100), subject capillary fingertip samples were tested in duplicate using 3 test strip lots; accuracy was assessed based on ISO 15197:2013 section 6.3 accuracy criteria (95% within ±15mg/dl or ±15% of reference for glucose <100 and ≥100mg/dl, respectively). In the clinical trial (N=219), untrained subjects with diabetes tested capillary fingertip and palm blood samples and completed an ease-of-use questionnaire. BGMS and YSI glucose analyzer results were compared based on ISO 15197:2013 section 8 accuracy criteria. RESULTS: In the laboratory study, 100% of results met ISO 15197:2013 section 6.3 accuracy criteria. In the clinical trial, 98.6% of capillary fingertip and 97.2% of palm results from subjects met ISO 15197:2013 section 8 accuracy criteria. By Parkes-Consensus Error Grid analysis, 100% of subject capillary fingertip results were within Zone A. Based on questionnaire results, the majority of subjects found the BGMS easy to use. CONCLUSIONS: The BGMS exceeds ISO 15197:2013 section 6.3 and section 8 accuracy criteria in the laboratory and in the hands of untrained users with diabetes.

Clinical performance and safety of adapters for intradermal delivery with conventional and autodisable syringes.

Although the number of vaccines and diagnostic tests currently delivered intradermally is limited, this route of administration offers potential advantages due to the high concentration of antigen-presenting cells in the skin. One factor which may in part be limiting development and use of intradermal (ID) administration is concern about the ease and reliability of the needle and syringe-based Mantoux technique. A phase I clinical study was conducted to evaluate two ID adapters that have been developed as injection-delivery aids to increase the safety, simplicity, and reliability of ID injection: a prototype autodisable, intradermal (ADID) adapter for autodisable (AD) syringes, and a marketed side-merge adapter (SMA). Thirty healthy adult volunteers each received six injections of 0.1 mL of sterile saline solution. Each adapter was used to give injections into the upper deltoid, forearm, and suprascapular regions of each volunteer. The needle-bevel orientation during injection was random. Injection performance was determined by measuring wheal size and fluid leakage. Wheals were similar in size for the ADID adapter (mean 9.9 ± 0.17 mm) and SMA (mean 9.8 ± 0.15 mm). In all of the injections completed with the SMA, and 98% of those completed with the ADID, fluid leakage was less than 10% of the intended injection volume. Minor skin abrasions were the only adverse events. Based on self-reporting of pain, injections were well tolerated (mean pain score of 2 on a 0-10 scale). ID delivery using the SMA and ADID adapters appears safe and effective.

Accuracy evaluation of contour next compared with five blood glucose monitoring systems across a wide range of blood glucose concentrations occurring in a clinical research setting.

BACKGROUND: This study evaluated the accuracy of Contour(®) Next (CN; Bayer HealthCare LLC, Diabetes Care, Whippany, NJ) compared with five blood glucose monitoring systems (BGMSs) across a wide range of clinically occurring blood glucose levels. SUBJECTS AND METHODS: Subjects (n=146) were ≥ 18 years and had type 1 or type 2 diabetes. Subjects' glucose levels were safely lowered or raised to provide a wide range of glucose values. Capillary blood samples were tested on six BGMSs and a YSI glucose analyzer (YSI Life Sciences, Inc., Yellow Springs, OH) as the reference. Extreme glucose values were achieved by glucose modification of the blood sample. System accuracy was assessed by mean absolute difference (MAD) and mean absolute relative difference (MARD) across several glucose ranges, with <70 mg/dL evaluated by MAD as the primary end point. RESULTS: In the low glucose range (<70 mg/dL), MAD values were as follows: Accu-Chek(®) Aviva Nano (Roche Diagnostics, Indianapolis, IN), 3.34 mg/dL; CN, 2.03 mg/dL; FreeStyle Lite(®) (FSL; Abbott Diabetes Care, Inc., Alameda, CA), 2.77 mg/dL; OneTouch(®) Ultra(®) 2 (LifeScan, Inc., Milpitas, CA), 10.20 mg/dL; OneTouch(®) Verio(®) Pro (LifeScan, Inc.), 4.53 mg/dL; and Truetrack(®) (Nipro Diagnostics, Inc., Fort Lauderdale, FL), 11.08 mg/dL. The lowest MAD in the low glucose range, from CN, was statistically significantly lower than those of the other BGMSs with the exception of the FSL. CN also had a statistically significantly lower MARD than all other BGMSs in the low glucose range. In the overall glucose range (21-496 mg/dL), CN yielded the lowest MAD and MARD values, which were statistically significantly lower in comparison with the other BGMSs. CONCLUSIONS: When compared with other BGMSs, CN demonstrated the lowest mean deviation from the reference value (by MAD and MARD) across multiple glucose ranges.

Performance variability of seven commonly used self-monitoring of blood glucose systems: clinical considerations for patients and providers.

BACKGROUND: Blood glucose data are frequently used in clinical decision making, thus it is critical that self-monitoring of blood glucose (SMBG) systems consistently provide accurate results. Concerns about SMBG accuracy have prompted the development of newly proposed International Organization for Standardization (ISO) standards: ≥ 95% of individual glucose results shall fall within ± 15 mg/dl of the results of the manufacturer's reference procedure at glucose concentrations <100 mg/dl and within ± 15% for values ≥ 100 mg/dl. We evaluated seven marketed systems against the current and proposed ISO criteria (criterion A). METHOD: Capillary blood samples were collected from 100 subjects and tested on seven systems: Accu-Chek Aviva Plus, Advocate Redi-Code, Element, Embrace, Prodigy Voice, TRUEbalance, and WaveSense Presto. Results were compared with manufacturer's documented reference system, YSI or perchloric acid hexokinase; three different strip lots from each system were tested on each subject, in duplicate. RESULTS: Compared against current ISO criteria (≥ 95% within ± 15 mg/dl for values <75 mg/dl and ± 20% for values ≥ 75 mg/dl) the Accu-Chek Aviva Plus, Element, and WaveSense Presto systems met accuracy criteria. However, only the Accu-Chek Aviva Plus met the proposed ISO criteria (criterion A) in all three lots. The other six systems failed to meet the criteria in at least two of the three lots, showing lot-to-lot variability, high/low bias, and variations due to hematocrit. CONCLUSIONS: Inaccurate SMBG readings can potentially adversely impact clinical decision making and outcomes. Clinicians can reduce controllable variables by prescribing accurate SMBG systems. Adherence to the proposed ISO criteria should enhance patient safety by improving the accuracy of SMBG systems.

Effect of sitagliptin on post-prandial glucagon and GLP-1 levels in patients with type 1 diabetes: investigator-initiated, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Peripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin (dipeptidyl peptidase-IV [DPP-IV] inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon. METHODS: This investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16 weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost™) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in glycated hemoglobin (A1c), CGM data, insulin dose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and C-peptide levels. RESULTS: There were no differences at screening between groups; however, after a 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<.001) and GIP levels lower (P = .03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 versus 16.0 ± 1.8; P = .006) in the sitagliptin group at 16 weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16 weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose, and time spent in hyperglycemia. CONCLUSION: Sitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose, or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a nonsignificant trend in decreasing hyperglycemia, which needs further evaluation.

Comparative glycemic control, safety and patient ratings for a new 4 mm x 32G insulin pen needle in adults with diabetes.

OBJECTIVE: Pen needles (PN) for subcutaneous insulin therapy have become smaller; 5 mm PNs are now the shortest in use. We evaluated the safety, efficacy and patient ratings of a new 4 mm x 32 gauge (G) PN. RESEARCH DESIGN AND METHODS: Subjects with type 1 and type 2 diabetes and HbA1c 5.5% to 9.5% participated in a randomized non-inferiority cross-over trial, at four U.S. centers. Subjects used 4 mm x 32G PNs and either 5 mm x 31G PNs (4/5 mm) or 8 mm x 31G PNs (4/8 mm) in two, 3-week treatment periods; order of needle use was controlled. Subjects were either 'low dose' or 'regular dose' users (highest single insulin dose