![]() ![]() A modest number of participants were enrolled, with crossover of the injection schedule (morning to evening or vice versa), so group size was limited, with a low power to detect differences between treatments-that is, the percentage of time within the glucose range of 80–140 mg/dL (the primary end point), glucose variability metrics, and post hoc analyses. This study also used a short duration of treatment (two 8-week periods), although a 2-week period of CGM (weeks 7–8 in this study) is considered to be representative of the longer-term pattern of glucose levels ( 17). Future studies could be enhanced by using the recently approved Gla-300 pen injector the use of syringes with Gla-300 might be expected to increase glucose variability in the Gla-300 group, although an increase in variability was not seen in this study. This exploratory CGM study has limitations: the open-label study design, which was unavoidable because of the different injection volumes of Gla-300 and Gla-100, and the use of commercial syringes that are not approved for use with Gla-300 in clinical practice and are suboptimal for delivery of an insulin with a concentration of 300 units/mL. In the current study, however, mean 24-h glucose profiles do not provide any indication of glucose levels being higher with Gla-300 than with Gla-100 at a time that might be considered “before breakfast.” In addition, the hypoglycemia results presented here could be influenced by the fact that mean interstitial glucose levels were higher with Gla-300 than Gla-100 at baseline, although this was likely offset by the greater decrease in glucose over the study period with Gla-300 and the lower final mean glucose in that group. ![]() The phase IIIa EDITION 4 study also investigated Gla-300 versus Gla-100 in people with type 1 diabetes and observed an increase in SMPG with Gla-300 before breakfast in the initial weeks of the study that might have affected the risk of hypoglycemia. There were no consistent within-treatment differences in terms of hypoglycemia risk between the morning and evening injection groups for either of the insulin preparations. During the nocturnal period, mealtime insulin would be expected to have minimal effect as a contributory factor, allowing a more reliable comparison of the effects of basal insulin. The annualized event rates for SMPG-confirmed or severe hypoglycemia were lower in the Gla-300 than Gla-100 group during the nocturnal period (0000–0559 h), which showed a risk reduction of 55% for confirmed (<54 mg/dL) or severe hypoglycemia. Rates of hypoglycemia detected using SMPG values were consistent with the interstitial glucose values detected by CGM. While glucose variability metrics were smaller for Gla-300 than Gla-100, consistent with the 24-h glucose profiles, there were no statistically significant differences in these metrics. The increase in glucose levels from 0200−0800 h in the Gla-100 morning injection group may be more pronounced than any glucose increases seen in the evening injection group as a result of the basal insulin waning toward the end of the 24-h dosing interval, which is not masked by the use of rapid-acting insulin during this early morning period. This difference in profile was even more evident when morning and evening injection groups were compared the glucose profiles of Gla-300 morning and evening injections are nearly superimposable, whereas larger excursions were seen in the morning injection group compared with the evening injection group for Gla-100. The mean 24-h glucose profile, averaged for all participants on CGM in each group by time of day, showed a narrower range of daily interstitial glucose levels for Gla-300 than for Gla-100. However, only a small percentage of individuals with type 1 diabetes who use these first-generation analogs achieve glycemic targets, and excursions into clinically dangerous hypoglycemic and hyperglycemic states are common ( 12). The first generation of basal insulin analogs have substantially improved glucose management, offering a prolonged duration of action and a lower risk of hypoglycemia, particularly overnight, compared with NPH insulin ( 11). The basal insulin can then be paired with a rapid-acting insulin before a meal that is adjusted to optimize glycemic control after the meal ( 10). To achieve this, the “ideal” basal insulin should provide stable glucose-lowering activity over an entire 24-h period and help maintain target glucose levels in the fasting state and before meals ( 9). A fundamental goal of type 1 diabetes management is to maintain glucose levels within a target range and to minimize vulnerability to hypoglycemic or hyperglycemic events that can lead to short- and/or long-term health complications ( 6– 8).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |