This is a non-interventional prospective study describing the practices associated with the initiation of insulin therapy in patients with T2DM whose condition was insufficiently controlled during treatment with oral antidiabetics drugs (OADs) under routine clinical practice conditions in the Czech Republic, for whom physicians decided to add basal insulin to the existing treatment regimen. Patients from 137 study centers across all regions of the Czech Republic and the Slovak Republic were eligible for entry, thereby ensuring the highest possible representativeness of the sample. Patients were enrolled into the study consecutively; the maximum number of patients per center was 15 and the minimum was five. All study procedures were carried out in accordance with the International Conference on Harmonization/Good Clinical Practice. All participants provided written informed consent. The study was conducted from June 2013 to December 2014 in the Czech Republic.
The inclusion criteria were a diagnosis of T2DM, age of > 18 years, insulin naïvety, insufficient control of the diabetes on the current therapeutic regimen of OADs (HbA1c ≥ 53 mmol/mol; DCCT > 7%), and the decision of a diabetologist to initiate basal insulin treatment with insulin glargine 100 U/mL, insulin detemir, or insulin neutral protamine Hagedorn (NPH). A signed written informed consent form was also required.
The exclusion criteria were type 1 diabetes mellitus, pregnancy at inclusion, use of short-acting insulin for therapeutic reasons for a duration of < 12 months, and treatment with glucagon-like peptide-1 analogs.
All patients were provided with a glucometer and self-monitored their blood glucose level.
Compliance with Ethics Guidelines
This study was conducted in accordance with the Declaration of Helsinki (2004) and the International Conference on Harmonization (ICH) Guidelines for Good Clinical Practice (1996). The study design was approved by the country-specific regulatory authorities and ethical committees. All participants of the study provided signed informed consent.
Insulins Used in the Study
None of the basal insulins available in the Czech Republic during the study period were excluded. The basal insulins included an intermediate-acting insulin (NPH) and long-acting insulin analogs (glargine 100 U/ml, detemir).
The primary objective of the study was to determine the percentage of patients after 6 months of therapy with basal insulin with a HbA1c level of < 53 mmol/mol (DCCT < 7%) in the overall participant population and in subgroups defined by baseline (pre-basal insulin) levels of HbA1c as follows:
International Federation of Clinical Chemistry (IFFC)-HbA1c < 64 mmol/mol (DCCT < 8%)
IFFC 64 to < 75 mmol/mol (DCCT 8 to < 9%)
IFFC ≥ 75 mmol/mol (DCCT ≥ 9%)
The secondary objectives were to determine the proportion of patients with hypoglycemic events, mean change of HbA1c from baseline to the 6-month follow-up visit, mean change in fasting plasma glucose levels from baseline to the 6-month follow-up visit, mean change in body weight, and mean change in doses of basal insulin in the overall participant population and each of the three subgroups. Probable hypoglycemic events were registered by patients, and documented hypoglycemic events were obtained from glucometer records by a physician (as per American Diabetes Association definitions ).
Data were collected at the inclusion visit (Visit 1 [V1]) and at routine follow-up visits (Visits 2 and 3 [V2, V3]) at 3 and 6 months, respectively. The diabetologists participating in the study documented data on each patient on electronic case report form. During V1, insulin therapy was initiated, dosage was recommended, basic anamnestic data were recorded, and a physical examination and blood sampling were conducted to analyze basic patient parameters. The patient was instructed on the insulin therapies and possible dose titration according to the usual practice of the specific physician. Specific study recommendations were advised regarding insulin dose and the method of dose titration. During V2 and V3, the dose of insulin currently used by the patient was recorded and, if necessary, recommendations were made to adjust the dose. HabA1C values were determined and recorded during all study visits.
Sample Size Determination
As no similar data in the Czech Republic on primary analysis were available, the assumptions for sample size estimation were based on results published by Zhou et al. 2009 . The assumed distribution of patients in the three subgroups of interest, namely, HbA1c 64 mmol/mol [DCCT < 8%], HbA1c 64–75 mmol/mol [DCCT 8 to < 9%], and HbA1c ≥ 75 mmol/mol [DCCT 9%]), was 25, 35, and 40%, respectively; the assumed rates of patients with target values of HbA1c after 6 months of basal insulin therapy in these HbA1c subgroups were 75, 55 and 35%, respectively. The intention was to enrol a total of 1500 patients into the study. The expectation was that about 15% of these patients would not have any post-baseline value of HbA1c, leaving 1300 patients eligible for the analysis.
The analysis of 1300 patients would allow the percentage of patients to be determined with a precision of at least 6% and probability of 80%. This would mean that at least a 3% half-width of 95% two-sided Wald confidence interval (CI) with continuity correction could be expected with a probability of at least 80%. Further, under the assumptions of the expected 25% rate of patients with a baseline HbA1c of ≤ 64 mmol/mol (DCCT ≤ 8%) and expected 75% rate of patients who achieved target HbA1c levels in this subgroup, the number of enrolled patients would allow determination of the percentage of responder patients with a precision of at least 10% and probability of 80%. This was the subgroup for which the precision would be the “worst.”
Statistical methods commonly used for analysis of epidemiological data were used. The two-sided confidence intervals were calculated. If appropriate, the 95% two-sided asymptotic Wald confidence interval with continuity correction was presented. All collected assessments were presented using descriptive statistics.