Glargine versus Degludec: two long-acting insulin analogs are compared for efficacy and side effects.
Long-acting basal insulin analogs have shown to have a longer duration of action, less variability, and lower hypoglycemia risks than NPH insulin. Basal insulin analogs like degludec 100 units/mL and glargine 300 units/mL have been created for an ultralong effect but have not been studied in comparison with each other for efficacy. Previous research showed the two drugs had similar HbA1c reduction but less hypoglycemia episodes. Those trials did not look at direct clinical comparisons. A new study conducted a head-to-head comparison of degludec (Deg-100) and glargine 300 (Gla-300).
Participants in the BRIGHT trial were randomized in a multicenter open-labeled active-controlled, parallel-group, noninferiority study. The study was 24-week and enrolled 920 adults with uncontrolled type 2 diabetes on oral antidiabetic medication. Uncontrolled diabetes was defined as HbA1C over 7.5% and less than 10.5% at screening. Participants were stratified by HbA1c level, sulfonylurea use, or glinide use. Patients self-administered subcutaneous injection of either Gla-300 or Deg-100 once daily at the same time. Starting doses were 0.2 units/kg for Gla-300 or 10 units for Deg-100 and were titrated to obtain glycemic targets, a fasting glucose level between 80 and 100 mg/dL. Titration to target levels occurred during weeks 0-12 and continued the rest of the trial if target levels still were not achieved.
At the end of the 24 weeks, the mean HbA1c for the Gla-300 group was reduced from 8.7 to 7.0. The mean HbA1c in the Dec-100 group decreased from 8.6 to 7.0. Least squares mean change in HbA1c was -1.64 for Gla-300 and -1.59 for Deg-100 with a mean difference of only -0.05%. This shows that Gla-300 is noninferior to Deg-100. Superiority of Gla-300 over Deg-100 was not demonstrated. Also, participants who reached an HbA1c less than 7 and had no hypoglycemic events were equal among the two groups. There was 66.5% of the Gla-300 group who had confirmed hypoglycemia events (<70 mg/dL) at any time in the day versus 69% among the Deg-100 group. Participants using sulfonylureas or glinides were no more likely to have hypoglycemic events than those who were not on these medications. Of note during the first 12 weeks, the rate of hypoglycemia was lower in the Gla-300 group versus the Deg-100 group.
Other endpoints that resulted from this trial were similar and included insulin dose averages, body weight gain, and adverse events. The mean daily insulin dose increases from day 1 to week 24 were 33.6 units for the Gla-300 group and 29.1 units for the Deg-100 group. Body weight gain among the Gla-300 group was an absolute mean increase of 2kg and Deg-100 had 2.3kg gain. Adverse events were also similar among the two groups with 43.7% in the Gla-300 group and 47.8% in the Deg-100 group experiencing an adverse event during the 24-hour period. Injection site reaction occurred in 1.7% and 1.3% of the Gla-300 and Deg-100 groups, respectively.
Results of this study showed glargine 300 and degludec 100 are similar in terms of HbA1c reduction and hypoglycemic incidence rates as well as adverse events. More studies in patients with more advanced type 2 diabetes are needed to show if these long-acting insulin analogs are still similar.
- Long-acting basal insulin analogs are similar in efficacy and side effects.
- When choosing between degludec 100 and glargine 300, cost and access should be considered.
- Both degludec 100 and glargine 300 had comparable glycemic control and low overall incidences of hypoglycemia.
Julio Rosenstock, Alice Cheng, Robert Ritzel, Zsolt Bosnyak, Christine Devisme, Anna M.G. Cali, Jochen Sieber, Peter Stella, Xiangling Wang, Juan P. Frías, Ronan Roussel, and Geremia B. Bolli. More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial. Diabetes Care. (Oct.2018)41, 10: 2147-2154. https://doi.org/10.2337/dc18-0559