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OBJECTIVE: To evaluate the safety and efficacy of basal insulin glargine using a basal-bolus regimen in a common clinical practice setting in the Czech Republic. PATIENTS AND METHODS: The LINDA project was a non-interventional, multicenter (n = 255), national, observational project. A total of 4,998 patients with Type 1 and 2 diabetes mellitus (T1DM, T2DM) with predominantly insulin therapy (99,7 %), after switch on insulin glargine at basal-bolus regimen, were enrolled in this project. The patients were followed up for 6 months after initiation of the therapy with insulin glargine. The primary objective of the project was to investigate the incidence of severe hypoglycemic episodes during the treatment with basal insulin analogue glargine (Lantus®) in a common clinical practice setting. The se-condary endpoints were changes in glycosylated hemoglobin (HbA1c) levels, fasting plasma glucose (FPG), body weight, insulin dose, change of number of hypoglycemic episodes in comparison the previous therapy and the frequency of adverse effects. RESULTS: Severe hypoglycaemia were observed during treatment with insulin glargine at 0.8 % patients. When comparing the incidence of hypoglycemia with the previous therapy, we demonstrated a clinically and statistically significant reduction in their frequencies. The percentage of patients with hypoglycemic episodes (17.6 %), severe hypoglycemia (0.8 %) and severe nocturnal hypoglycemia (0.3 %) over the last month of treatment with insulin glargine using the basal-bolus regimen was consistently lower compared to the last month of treatment before initiation of this therapy (42.5 %, 17.6 %, and 13.8 % of the patients, respectively). In patients with T1DM, the incidence of hypoglycemia decreased from 37.80 ± 15.95 episodes/patient/year to 8.76 ± 4.38 epi-sodes/patient/year (p < 0.001) for all hypoglycemic episodes; from 5.64 ± 3.27 episodes/patient/year to 0.0396 ± 0.012 episodes/patient/year (p < 0.001) for severe hypoglycemia; and from 3.84 ± 2.04 episodes/patient/year to 0.0096 ± 0.003 episodes/patient/year (p < 0.001) for severe nocturnal hypoglycemia. In patients with T2DM, the incidence of hypoglycemia decreased from 12.48 ± 7.57 episodes/patient/year to 1.68 ± 0.78 episodes/patient/year (p < 0.001) for all hypoglycemic episodes; from 2.04 ± 0.94 episodes/patient/year to 0.0132 ± 0.005 episodes/patient/year (p < 0.001) for severe hypoglycemia; and from 1.32 ± 0.77 episodes/patient/year to 0.0048 ± 0.0008 episodes/patient/year (p < 0.001) for severe nocturnal hypoglycemia. A statistically significant improvement in the metabolic control was demonstrated when using insulin glargine. The glycated hemoglobin (HbA1c) decreased from 7.74 ± 1.71 % to 6.43 ± 1.39 % ( -1.31 ± 0.32 %, p < 0.001) in patients with T1DM, and from 8.13 ± 1.56 % to 6.72 ± 1.40 % ( -1.41 ± 0.28 %, p < 0.001) in patients with T2DM. A statistically significant (p < 0.001) increase in the number of patients with HbA1c < 5.4 % was further demonstrated. The decrease in fasting blood glucose (FBG) and 6-point blood sugar profile was also statistically significant in both types of diabetes (p < 0.001). Changes in therapy and subsequent treatment with insulin glargine were perceived positively by both physicians and patients. CONCLUSION: In the common clinical practice setting, the initiation of treatment with insulin glargine using the basal-bolus regime in patients with previous insulin therapy resulted in a reduction in the incidence of hypoglycemic events, including severe hypoglycemia and severe nocturnal hypoglycemia, and improved metabolic control in patients with diabetes (reduced glycated hemoglobin, fasting glucose values and 6-point blood glucose profile). Greater satisfaction with the current treatment was reported by both patients and physicians.Key words: basal-bolus regimen - diabetes mellitus - insulin glargine - observational project.
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BACKGROUND: Glucose variability combined with glycosylated hemoglobin (HbA1c) assessments more reliably represents the level of glycemic control. The study was aimed to compare blood glucose variability with insulin glargine vs. neutral protamine Hagedorn (NPH) in patients with type 2 diabetes mellitus using a continuous glucose-monitoring system (CGMS), in patients treated with basal insulin using stable dose of oral antidiabetic agents and HbA1c in the range of 4.5-8.0 % International Federation of Clinical Chemistry (IFCC) units. [6.2-9.4 % Diabetes Control and Complications Trial (DCCT) units]. METHODS: This was a multicenter, prospective, open-label, single-arm study in patients (N = 116) treated for ≥ 2 months with NPH and metformin combined with sulfonylurea or glinide. Glucose variability was measured after a 4-week NPH treatment phase and after a subsequent 12-week glargine treatment phase using CGMS. Based on 72-hour CGMS, glucose variability was assessed by area under the curve [AUC (mmol/L · h)]. Differences (glargine-NPH) in AUC within 24 h in the glucose ranges of ≤ 3.3, ≤ 3.9, 7.5-3.9 (margins excluding), ≥ 7.5, ≥ 10, and ≥ 15 mmol/L were evaluated. Circadian fluctuation of glucose was assessed by M-value (log-transformation of the deviation from an arbitrary standard). RESULTS: AUCs of glucose in the lowest ranges (≤ 3.3 and ≤ 3.9 mmol/L) did not change significantly after treatment with glargine. Those in the higher ranges (≥ 7.5, ≥ 10, and ≥ 15 mmol/L) were significantly lower (p < 0.001 for all ranges), whereas AUC of glucose in the normal range (3.9-7.5 mmol/L) was significantly higher (p < 0.001) at the end of glargine treatment phase. Circadian fluctuation of glucose assessed by M-value showed a significant decrease after glargine treatment (p < 0.003). No significant differences in hypoglycemia confirmed by glucose value ≤ 3.3 mmol/L were found between treatment phases. This trial is registered at ClinicalTrials.gov, NCT00659477. CONCLUSIONS: As monitored by CGMS, switching from NPH to glargine with active titration shifted glucose from abnormally high to normal levels with reduced fluctuation and without increased risk of hypoglycemia.
