In this RCT, the use of pens to apply insulin among elderly patients with uncontrolled T2D seems to reduce further glycated hemoglobin compared to the use of syringes. However, there was no difference in the other outcomes analyzed.
Both group of treatment had significant improvement in glycemic control over 24 weeks. This result reinforces that insulin, regardless of device used, improves the control. The superiority of pens can be understood based on the difference between baseline and 24 weeks. At the end of the study glycated hemoglobin was not statistically different between groups (8.39 vs 8.85% for PG and SG respectively). These final values for glycemic control are far off the ideal target for these patients. However, considering the participants were elderly, with a high prevalence of chronic complications, strict glycemic control could bring more risks [5, 6] and additionally in this study we did not have a target to reach.
The occurrence of hypoglycemia cannot be neglected. With advancing age, the number of episodes seems to increase, regardless of glycemic control [12]. We did not detect a difference in relation to the occurrence of hypoglycemia. High levels of HbA1c along the follow-up may contributed to the low frequency of hypoglycemia in both groups. Another factor that limited this analysis was the way of measuring hypoglycemia. The episodes were computed if recorded by patients. Unrecorded episodes could not be confirmed. Due to the small number of episodes, the presence of nocturnal, asymptomatic and severe hypoglycemia, we could only assess if the patient reported or not during the last month. There was no possibility of quantifying the number of severe, asymptomatic and nocturnal hypoglycemia episodes.
In relation to the evaluation of adherence, we were careful to accurately measure the number of insulin units used in each visit. The method used ensures that we find the closest value to the amount of insulin used in the previous month. Therefore, the degree of adhesion found in our study seems precise. We considered adequate adherence if the patient used at least 80% of the prescribed insulin dose in the previous month. Unlike patients with recent insulin use [4], method of application seems did not have much influence among patients using insulin for several years. Although there is no difference between groups, there was a tendency to be more adherent during the course of the study in both groups and our results were similar to other studies [5, 7, 12,13,14,15]. Training to use insulin in addition to frequent adjustments of insulin doses, may have contributed to this result.In association with the reduction of HbA1c, there was an increase in the amount of insulin used per kilo. We realize that the more frequent follow-up (monthly medical visits) in search of the glycemic target contributed to this result. At each visit, participants performed capillary blood glucose tests. Based on these notes, the researcher adjusted the dose of insulin. The low number of hypoglycemic episodes enabled us to increase insulin doses almost every visit. In addition, the apparent increase in PG may have been influenced by the ease of use of the method. Even without the blinded evaluator, we used a pre-defined protocol in both groups for treatment adjustment. However, there was an increase of 0.17 IU/kg/day in PG and 0.11 IU/kg/day in SG. These values appear not to have clinical significance, but should be considered.
In the Brazilian Public Health System, patients depend on free medication. In general, only metformin and sulfonylureas are available as oral drugs. For this reason, insulin is introduced into the treatment prior to prescribing other oral third class medication. In selected cases, even with metformin alone, insulin prescription is required to achieve satisfactory glycemic control. Either way, ADA [2] recommends the use of NPH and Regular insulin in developing countries, when the financial condition does not favor other treatment. We chose not to include patients in the use of insulin analogues for this reason. This study allows us to assess the reality of patients with diabetes in our country.
Recently, the use of insulin pens has been approved in Public Health System, which may also aid in treatment. Regarding the measurement of capillary glycemia, there is no consensus in the literature on the recommendation of frequency or effect among patients with T2D using insulin [16,17,18]. However, it is expected that for the proper adjustment of doses, this strategy will be present. However, it is not available to all patients in Brazil. In addition, access to public health care is a limiting factor in the Brazilian reality. Patients have specialist appointments every 4 to 6 months, with less frequent treatment adjustments than optimal to achieve satisfactory glycemic levels.
The greatest difficulty in relation to the assessment of Quality of Life and the impact of the disease was the interpretation of the questionnaires. Some of the patients had no perception of poor disease control and, for that reason, they responded as being satisfied with their health conditions. In a previous study, although patients had inadequate glycemic control, there was no perception of obstacles to treatment or understanding of the disease. [9] On the other hand, this perception made scores low on the first visit, not allowing the detection of improvement in quality of life during the study. Informally, patients who used pens appeared more satisfied throughout the study, but this was not reflected in the questionnaires. One of the probable reasons for this difference not being found is due to the small number of participants. In future studies, this assessment may be better understood. Despite the difficulties encountered, these questionnaires are validated for use in Brazil. All participants were able to answer completely.
Our main limitation was not to have blindness of the evaluators. Despite the use of care protocol to minimize the influence of this lack, there may have been influence on patient care and insulin doses. We chose not to blind the evaluator to ensure that all patients were treated, face to face, by the same investigator. The blinding of the researcher who made the treatment adjustment could harm the patient's medical relationship. Another limitation was the difficulty that some patients had to perform Self-monitoring of Blood Glucose due to visual or cognitive problems. In some cases, treatment adjustment was delayed. Some patients also had difficulty using their pens at first. However, at all visits the application technique was reviewed in both groups. Independently, patients who were not able to self-administer insulin were excluded before the intervention started. Regarding randomization, the initial treatment regimen was not stratified. However, the groups were quite similar, mainly in relation to the use of insulin and classes of oral antihyperglycemic agents. Regarding the statistical analysis, both groups showed similar results in absolute values of HbA1c in each evaluation. The large SD of the sample represents great variability, even with normal distribution, and small sample, despite the statistical power achieved with the calculated sample size. If the sample were larger, the SD could be reduced and even with a statistical difference found between the groups. The greatest reduction in PG was only in the delta of HbA1c reduction.
Few patients had not used insulin prior to the study. Analyzes without these patients were like results presented. Another limitation was the need to use a fixed protocol to adjust insulin doses. This option was taken to minimize the effect of the lack of blinding by the evaluators. The progressive increase in insulin doses was similar among patients, regardless of whether the glycemia value was higher or closer to the target. Thus, perhaps patients with less control needed more time to achieve blood glucose levels close to those desired.