Modulation of insulin dose titration using a hypoglycaemia-sensitive algorithm: insulin glargine versus neutral protamine Hagedorn insulin in insulin-naïve people with type 2 diabetes.

AIMS: To examine whether insulin glargine can lead to better control of glycated haemoglobin (HbA1c) than that achieved by neutral protamine Hagedorn (NPH) insulin, using a protocol designed to limit nocturnal hypoglycaemia. METHODS: The present study, the Least One Oral Antidiabetic Drug Treatment (LANCELOT) Study, was a 36-week, randomized, open-label, parallel-arm study conducted in Europe, Asia, the Middle East and South America. Participants were randomized (1:1) to begin glargine or NPH, on background of metformin with glimepiride. Weekly insulin titration aimed to achieve median prebreakfast and nocturnal plasma glucose levels ≤5.5 mmol/l, while limiting values ≤4.4 mmol/l. RESULTS: The efficacy population (n = 701) had a mean age of 57 years, a mean body mass index of 29.8 kg/m², a mean duration of diabetes of 9.2 years and a mean HbA1c level of 8.2% (66 mmol/mol). At treatment end, HbA1c values and the proportion of participants with HbA1c <7.0 % (<53 mmol/mol) were not significantly different for glargine [7.1 % (54 mmol/mol) and 50.3%] versus NPH [7.2 % (55 mmol/mol) and 44.3%]. The rate of symptomatic nocturnal hypoglycaemia, confirmed by plasma glucose ≤3.9 or ≤3.1 mmol/l, was 29 and 48% less with glargine than with NPH insulin. Other outcomes were similar between the groups. CONCLUSION: Insulin glargine was not superior to NPH insulin in improving glycaemic control. The insulin dosing algorithm was not sufficient to equalize nocturnal hypoglycaemia between the two insulins. This study confirms, in a globally heterogeneous population, the reduction achieved in nocturnal hypoglycaemia while attaining good glycaemic control with insulin glargine compared with NPH, even when titrating basal insulin to prevent nocturnal hypoglycaemia rather than treating according to normal fasting glucose levels.

Effects of insulin glargine versus metformin on glycemic variability, microvascular and beta-cell function in early type 2 diabetes.

We investigated whether basal insulin as first-line treatment in recently diagnosed type 2 diabetes (T2D) can improve glucose control, microvascular function and preserve insulin secretion in comparison with metformin (MET). In this open-label, randomized, prospective 36-week study, 75 patients (44 m, 31 f, mean age 60.7 ± 9.2 year) were allocated to treatment with either MET 1,000 mg b.i.d. (n = 36) or insulin glargine (GLA) at bedtime (n = 39). At baseline and study end, we performed a continuous glucose monitoring for assessment of interstitial glucose (IG) and measured microvascular function using Laser-Doppler fluxmetry. GLA versus MET treatment resulted in a more pronounced reduction in FPG (Δ: 3.1 ± 2.5 vs. 1.4 ± 1.5 mmol/l; p < 0.001) and overall IG (Δ AUC. 671 ± 507 vs. 416 ± 537 mmol/l min; p = 0.04). Postprandial PG and IG differences after a standardized test meal did not reach significance. Proinsulin/C-peptide and HOMA B as marker of endogenous insulin secretion were significantly more improved by GLA. Microvascular blood flow improved only in MET-treated patients. Early basal insulin treatment with GLA in T2D patients provided a better control of FPG, overall IG load and biomarker of beta-cell function compared to the standard treatment with MET. MET treatment resulted in an improvement of microvascular function. Studies of longer duration are needed to evaluate the durability of glucose control and ß cell protection with early GLA treatment.

Relationship between HbA1c on target, risk of silent hypoglycemia and glycemic variability in patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to compare time spent at low glucose level (silent hypoglycemia, glucose <3.0 mmol/l) and glycemic variability in patients who reached HbA1c <7.0% with those who did not. RESEARCH DESIGN AND METHODS: In 108 type 2 diabetic patients the interstitial glucose concentration was measured with CGMS (Continuous Glucose Monitoring System) over 72 h. Patients were divided in group 1 with an HbA1c <7.0% (n=63) and group 2 with an HbA1c≥7.0% (n=45). RESULTS: 24% in group 1 experienced silent hypoglycemia vs. 11% in group 2 (n. s.), duration of silent hypoglycemia over 48 h was 27±71 min vs. 7±36 min (n. s.). This was also valid for the subgroups treated with insulin. Patients in group 2 had a significantly higher standard deviation of average glucose (2.3±0.8 vs. 1.3±0.6; p<0.001) and MAGE (mean amplitude of glycemic excursions) (4.8±2.1 vs. 2.6±1.1; p<0.001). CONCLUSION: Silent hypoglycemia tended to occur more often and to last longer in patients with HbA1c <7%. However, patients with HbA1c >7% had a higher glycemic variability. HbA1c >7% wasn't a reliable indicator of lower risk of hypoglycemia.

[Evaluation of a new disposable insulin pen and injection habits of diabetes patients in everyday clinical practice]. / Bewertungeines neuen Insulin-Fertigpens und Injektionsgewohnheiten von Diabetikern in der täglichen Praxis. Ergebnisse zweierAnwendungsbeobachtungen in Deutschland.

UNLABELLED: Evaluation of a new disposable insulin pen and injection habits of diabetes patients in everyday clinical practice BACKGROUND: Injection devices (pens) for insulin application play a major role in treatment acceptance and adherence in insulin-treated diabetes patients. The mechanical disposable pen SoloStar containing the insulin analogs glargine or glulisine (each 100 IE/ml) provides modern design with user-friendly handling features. METHODS: In two independent, non-interventional, observational studies conducted nation-wide between April and December 2007 in outpatient practices, patients with diabetes newly instructed on how to use the pen were interviewed by their trainers (physicians, diabetes consultants) after approx. 6-8 weeks of pen use to give feedback on technical deficiencies, handling problems with the pen, injection habits, as well as on pen properties. Trainers were also asked to assess pen properties and particularly to document the time required for pen training. The evaluation applied a grading system similar to that used in German schools (1: very good; 6: very insufficient/failed). Furthermore, trainers were asked to retrospectively record any adverse events occurring during the observational period. RESULTS: A total of 2,412 trainers from 1,626 centres and 8,428 patients (80% type 2) participated in the studies. In each study 0.5% of patients reported 41 and 19 technical problems with the pen, respectively. Similarly 3% of patients from each study reported handling problems. Recommended changes of needles and safety checks of the pen before each injection were performed by 40% and max. 25% of the patients, respectively. The features of the new disposable pen were all rated "very good" to "good" by the majority of patients and trainers. The best rated features were usability, dose adjustment and the low effort for the dose release. Pen training of patients were rated as "very simple" or "simple" by the training staff and average instruction time was reported not to exceed more than 10 minutes for the majority of patients. In 19 patients (0.2%) a total of 34 adverse events were documented. CONCLUSION: The results of these two observational studies showed no relevant technical deficiencies and handling problems associated with the new disposable pen in everyday clinical practice. Ease of use and little time required for pen training may contribute to a high acceptance and satisfaction by the patients and training staff. Injection habits, however, indicated that patients did not well comply with recommendations given for needle changes and safety tests.

[Costs of antihyperglycemic drugs and consumables and treatment satisfaction in patients with type 2 diabetes. Results of the health care research study LIVE-DE (long-acting insulin glargine compared with NPH insulin in Germany)]. / Kosten für antihyperglykämische Arznei- und Verbrauchsmittel und Therapiezufriedenheit bei Typ-2-Diabetes. Ergebnisse der Versorgungsforschungsstudie LIVE-DE.

BACKGROUND: Economic aspects and patient-reported outcomes play an increasing role in the choice of therapeutic options. The aim of the LIVE-DE study (Long-acting insulin glargine versus NPH insulin cost evaluation in Germany[DE]) was to assess expenditures incurred in the care of diabetic patients, as well treatment satisfaction of patients with type 2 diabetes treated with insulin glargine (GLAR) or NPH insulin (NPH). PATIENTS AND METHODS: A retrospective, non-interventional, cross-sectional study was undertaken in Germany of 1,602 insulin-treated patients (982 on GLAR, 620 on NPH), enrolled from 199 randomly selected general practitioner or internal medicine specialist practices. Total cost of diabetes care (insulins, oral antidiabetic drugs, glucagon use, consumables for insulin administration and blood glucose self-monitoring devices) were calculated from total recorded expenditures, for a period of six months, from the perspective of statutory health insurance. Cost data were obtained from publicly available sources, based on the prices in the year 2007. Patient treatment satisfaction was assessed using previously validated questionnaires (SF-12, PAID, DTSQ, ITEQ). RESULTS: Physicians prescribed GLAR more often than NPH combined with oral antidiabetic drugs (43 % vs 16%), whereas NPH was more often used in an intensified insulin regimen compared to GLAR (79 % vs 49%). The mean total costs per patient over six months were lower in GLAR than NPH treated patients (658258 vs 685242 Euros [EUR]; p<0.001). The higher drug costs for basal insulin in the GLAR group (19497 vs 11674 EUR) were counterbalanced by lower costs for bolus insulin (96133 vs 158133 EUR), test strips (287137 vs 321142 EUR) and needles (4031 vs 4640 EUR). Only in the NPH group was glucagon use documented (in four patients). Patients treated with GLAR reported significantly higher treatment satisfaction. After adjustment of empirical results (by analysis of covariance), mean total costs of diabetes were higher in GLAR patients (+73.1 EUR; p<0.001). But treatment satisfaction remained significantly higher with GLAR. CONCLUSION: Based on the comparison of total diabetes treatment costs under real-life conditions between glargine and NPH insulin based treatment regimens, these results indicate that the choice of a given treatment should be determined by medical advantages and patients' preferences. Because of a lower injection rate and a higher patient treatment satisfaction, the use of glargine as first-line therapeutic approach is justified in order to achieve target glycemic control in insulin dependent type 2 diabetics.

Thin-layer chromatographic determination of monensin in feeds: screening method.

Monensin is extracted from feed with methanol and purified by solvent-partitioning solid-phase extraction. After solvent reduction, monensin is separated by thin-layer chromatography on silica gel and visualized by color development with vanillin. No false-positive results were obtained in validation studies by submitting or peer laboratories when blank samples were analyzed. Three of 20 samples spiked with 5 ppm monensin were reported as containing no monensin. All samples spiked with 10 ppm monensin were reported positive for monensin.