Degludec Basal Insulin Update
The American Association of Clinical Endocrinologists recently held their annual meeting in Phoenix, Arizona. Degludec, innovative basal insulin, continues to demonstrate much promise in evidence-based research studies. Helena Rodbard, MD, an adult endocrinologist in our DC neighborhood, along with Handelsman, Gough, Hobbs, Korsholm, and Lane, submitted a timely abstract: “Reduced Risk of Nocturnal Confirmed Hypoglycemia with insulin Degludec vs. Insulin Glargine (Lantus) in patients with type 1 diabetes requiring high doses of basal insulin: a meta-analysis of two randomized trials.”
The objective of the study was to compare “hypoglycemia rates for Degludec and Glargine in a subset of type 1 diabetes patients requiring high once-daily doses.”
According to the authors, a previous prospective meta-analysis of phase 3a trials comparing degludec with glargine demonstrated degludec to be associated with a 17 percent lower rate of nocturnal confirmed hypoglycemia across the entire treatment period (not statistically significant) and a significant 25 percent lower rate (P<0.05-statistically significant) after stable glycemic control and insulin dose was achieved (after 4 months).
How did the authors perform the study?
A patient level meta-analysis of both phase 3a and randomized treat-to-target trials, in which once daily degludec and glargine were compared in patients with type 1 diabetes. Trials were open-label (study participants knew which insulin they were taking) and 26 or 52 weeks in duration. Inclusion criteria necessitated receiving degludec or glargine doses of greater than 0.45 units/kg at the end of the trial.
What were the results?
- 25 percent (235/950) of patients received an end-of-trial basal insulin dose >0.45 units/kg.
- Mean end-of-trial basal insulin was similar for degludec (0.63 units/kg) and glargine (0.65 units/kg).
- Patients achieved similar mean end-of-trial hb A1cs with degludec and glargine: 7.41% and 7.55%, respectively.
- Mean end-of-trial fasting blood sugars were similar with degludec and glargine (133 mg/dL, 136mg/dL, respectively).
- Rates of overall confirmed hypoglycemia (Blood sugar<56 mg/dL or severe) were similar for degludec and glargine in the full trial period and maintenance period.
- Degludec was associated with significantly lower rates of nocturnal confirmed hypoglycemia (between 12:01 am and 5:59 am) by 36 percent in the full trial period (p=0.046 statistically sign cant) and by 44 percent in the maintenance period (p=0.033-significant)
What may we conclude from this study?
Patients that require high amounts of degludec (>0.45 units/kg) obtain similar overall glycemic control as those who have received glargine, but with significantly lower rates of nocturnal confirmed hypoglycemia than patients receiving similar high doses of glargine.
How may we apply these results?
This study was conducted in adults with type 1 diabetes that receive >0.45 units/kg of degludec or glargine. In most youth with type 1 diabetes, total insulin requirements range from 0.5 units/kg to 1.5 units/kg depending on developmental stage (toddler, latency period, adolescence, young adult, etc.). The amount of basal insulin may range from 25 to 50 percent of the total daily dose in our children and youth with diabetes. Thus, amounts of > 0.45 units/kg are not unusual.
It has been my experience that nocturnal hypoglycemia is the biggest fear of all patients, let alone parents of children and youth with diabetes. If there is any means by which we can decrease the risk of hypoglycemia overnight, improvement of quality of life for both the children with diabetes as well as their parents would be considerable. It appears that degludec is a very promising basal insulin with a statistically significant reduction in overnight hypoglycemia. What remains to be seen is its application in basal/bolus therapy. Dosing frequency is yet to be determined due to it having more than 24 hour action.
I will continue to keep you updated about degludec as it moves through the research trial process and eventually tested in youth with diabetes.