Impact of Blood Glucose Monitoring System Accuracy on Clinical Decision Making for Diabetes Management.

BACKGROUND: The accuracy of blood glucose monitoring systems (BGMS) is crucial for the safe and effective management of diabetes mellitus. Despite standardization of accuracy assessment procedures and requirements, various studies have shown that the accuracy of BGMS on the market can vary considerably. This article therefore provides health care professionals and users with an intuitive illustration of the impact of BGMS accuracy on clinical decision making. MATERIAL AND METHODS: Several hypothetical patient scenarios based on blood glucose (BG) levels in the low, normal, and high BG range are devised. Using data from a recent BGMS accuracy study, a method for calculating the expected range of BG readings from four examined BGMS at the selected BG levels is introduced. Based on these ranges, it is illustrated how clinical decisions and subsequent outcomes of the hypothetical patients are affected by the expected inaccuracies of the BGMS. RESULTS: The range of expected BGMS readings for the same true BG level can vary considerably between different BGMS. The discussion of hypothetical patient scenarios revealed that the use of some BGMS could be associated with an increased risk of adverse events such as failure to detect hypoglycemia, driving with an unsafe BG level, delay of treatment intervention in diabetes during pregnancy, or the failure to prevent diabetic ketoacidosis. CONCLUSIONS: This article can support both health care professionals and patients to understand the impact of BGMS accuracy in a relatable, clinical context. Furthermore, it is suggested that current accuracy requirements might be insufficient for the prevention of adverse clinical outcomes in certain circumstances.

Accuracy Beyond ISO: Introducing a New Method for Distinguishing Differences Between Blood Glucose Monitoring Systems Meeting ISO 15197:2013 Accuracy Requirements.

BACKGROUND: Diabetes treatment is intended to maintain near-normal glycemic levels. Self-monitoring of blood glucose (SMBG) allows patients to track their BG levels compared with glycemic targets and is associated with improved health outcomes. Because of the importance of SMBG, it is essential that results are accurate to prevent errors in nutritional intake and drug dosing. This study presents a new methodology to evaluate the accuracy of BG monitoring systems (BGMSs). METHODS: Sensitivity analyses were performed using real and simulated BGMS data to compute probabilities that, for any BG value, the BGMS result would be within prescribed error bounds and confidence limits compared with laboratory reference values. Multiple BG value ranges were used. RESULTS: Probability curves were created using data from 3 simulated BGMSs and anonymized data from 3 real-world BGMSs. Accuracy probability curves from capillary fingertip blood samples (actual clinical data) showed that all 3 real-world BGMSs met EN ISO 15197:2015 accuracy criteria, since 99.63%, 99.63%, and 99.81% of results from the 3 BGMSs were within ±15 mg/dL or ±15% of reference for BG <100 mg/dL and ≥100 mg/dL, respectively. However, there was identifiable variability between BGMSs if BG was <70 mg/dL; one BGMS showed further reductions in accuracy if BG was <50 mg/dL. CONCLUSIONS: Probability curves highlight the importance of BGMS accuracy to help achieve optimal glycemic control while avoiding hypoglycemia or hyperglycemia. This may be especially significant in very low BG ranges where small errors in BGMS measurements can have substantial impacts on patient-related outcomes, including hypoglycemia risk.

Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.

OBJECTIVE: Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration. RESEARCH DESIGN AND METHODS: In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6-6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day). RESULTS: Randomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c changes were noninferior for exenatide compared with lispro (-1.13 and -1.10%, respectively); treatment differences were -0.04 (95% CI -0.18, 0.11) in per-protocol (n = 510) and -0.03 (95% CI -0.16, 0.11) in intent-to-treat (n = 627) populations. FG was lower with exenatide than lispro (6.5 vs. 7.2 mmol/L; P = 0.002). Weight decreased with exenatide and increased with lispro (-2.5 vs. +2.1 kg; P < 0.001). More patients reported treatment satisfaction and better quality of life with exenatide than lispro, although a larger proportion of patients with exenatide experienced treatment-emergent adverse events. Exenatide resulted in fewer nonnocturnal hypoglycemic episodes but more gastrointestinal adverse events than lispro. CONCLUSIONS: Adding exenatide to titrated glargine with metformin resulted in similar glycemic control as adding lispro and was well tolerated. These findings support exenatide as a noninsulin addition for patients failing basal insulin.

Effects of exenatide on measures of ß-cell function after 3 years in metformin-treated patients with type 2 diabetes.

OBJECTIVE: We previously showed that exenatide (EXE) enhanced insulin secretion after 1 year of treatment, relative to insulin glargine (GLAR), with a similar glucose-lowering action. These effects were not sustained after a 4-week off-drug period. This article reports the results after additional 2 years of exposure. RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomized to EXE or GLAR. Forty-six patients entered the 2-year extension study in which they continued their allocated therapy. Thirty-six completed (EXE: n = 16; GLAR: n = 20) the 3-year exposure period. Insulin sensitivity (M value) and ß-cell function were measured by euglycemic hyperinsulinemic clamp followed by hyperglycemic clamp with arginine stimulation at pretreatment (week 52) and 4 weeks after discontinuation of study medication (week 56 and week 172). First-phase glucose stimulated C-peptide secretion was adjusted for M value and calculated as the disposition index (DI). RESULTS: At 3 years, EXE and GLAR resulted in similar levels of glycemic control: 6.6 ± 0.2% and 6.9 ± 0.2%, respectively (P = 0.186). EXE compared with GLAR significantly reduced body weight (-7.9 ± 1.8 kg; P < 0.001). After the 4-week off-drug period, EXE increased the M value by 39% (P = 0.006) while GLAR had no effect (P = 0.647). Following the 4-week off-drug period, the DI, compared with pretreatment, increased with EXE, but decreased with GLAR (1.43 ± 0.78 and -0.99 ± 0.65, respectively; P = 0.028). CONCLUSIONS: EXE and GLAR sustained HbA(1c) over the 3-year treatment period, while EXE reduced body weight and GLAR increased body weight. Following the 3-year treatment with EXE, the DI was sustained after a 4-week off-drug period. These findings suggest a beneficial effect on ß-cell health.

One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress.

OBJECTIVE: The objective of the present study was to investigate the effects of one-year treatment with exenatide or Insulin Glargine, followed by a 5-week off-drug period, on postprandial lipidaemia, glycaemia and measures of oxidative stress. METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomised (using apermuted block randomisation scheme stratified by site and baseline HbA(1c) stratum (< or = 8.5% or >8.5%) of which 60 completed (exenatide n=30; Insulin Glargine n=30) the pre-treatment and on-drug meal test. Postprandial glucose, lipids and lipoproteins, and oxidative stress markers were studied at week -1, 51, and after a 5-week off-drug period following a breakfast and lunch mixed-meal containing 50 g fat, 75 g carbohydrates, and 35 g protein. RESULTS: 51-Week exenatide treatment resulted in a significant reduction of prandial glucose, triglycerides, apo-B48, calculated VLDL-C, FFA and MDA excursions whereas Insulin Glargine predominantly reduced fasting glucose, FFA and MDA. Changes in markers of oxidative stress were related to changes in postprandial glucose and triglyceride excursions, independent of treatment arm. All postprandial measures returned to pre-treatment values in both groups after 5-week cessation of study treatment. CONCLUSION: Exenatide showed beneficial effects on postprandial glycaemia and lipidaemia, and these effects were related to changes in the oxidative stress markers MDA and oxLDL during one year of treatment as compared to Insulin Glargine. Following cessation of both exenatide and Insulin Glargine measures returned to pre-treatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.

Exenatide affects circulating cardiovascular risk biomarkers independently of changes in body composition.

OBJECTIVE: To study the effect of exenatide on body composition and circulating cardiovascular risk biomarkers. RESEARCH DESIGN AND METHODS: Metformin-treated patients with type 2 diabetes (N = 69) were randomized to exenatide or insulin glargine and treated for 1 year. Body composition was evaluated by dual-energy X-ray absorptiometry. Additionally, body weight, waist circumference, and cardiovascular biomarkers were measured. RESULTS: Treatment with exenatide for 1 year significantly reduced body weight, waist circumference, and total body and trunkal fat mass by 6, 5, 11, and 13%, respectively. In addition, exenatide increased total adiponectin by 12% and reduced high-sensitivity C-reactive protein by 61%. Insulin glargine significantly reduced endothelin-1 by 7%. These changes were statistically independent of the change in total body fat mass and body weight. CONCLUSIONS: Exenatide treatment for 1 year reduced body fat mass and improved the profile of circulating biomarkers of cardiovascular risk. No significant changes were seen with insulin glargine except a trend for reduced endothelin-1 levels.

One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial.

OBJECTIVE: Traditional blood glucose-lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients. Preclinical studies with exenatide have suggested sustained improvements in beta-cell function. We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp-derived measures of beta-cell function, glycemic control, and body weight. RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomly assigned to exenatide (n = 36) or insulin glargine (n = 33). beta-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0, at week 52, and after a 4-week off-drug period. Additional end points included effects on glycemic control, body weight, and safety. RESULTS: Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold (95% CI 2.09-2.90, P < 0.0001) greater after a 52-week exenatide treatment compared with insulin glargine treatment. Both exenatide and insulin glargine reduced A1C similarly: -0.8 +/- 0.1 and -0.7 +/- 0.2%, respectively (P = 0.55). Exenatide reduced body weight compared with insulin glargine (difference -4.6 kg, P < 0.0001). beta-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy. CONCLUSIONS: Exenatide significantly improves beta-cell function during 1 year of treatment compared with titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, beta-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.