CONCLUDE: a trial COmparing the efficacy aNd safety of insulin degLUDEc and insulin glargine 300 units/mL in subjects with type 2 diabetes mellitus inadequately treated with basal insulin and oral antidiabetic drugs
Thomas Pieber, MD
Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria Athena Philis-Tsimikas, MD
Scripps Whittier Diabetes Institute, La Jolla, CA, USA
New longer-acting basal insulin analogues such as insulin degludec (degludec) and insulin glargine 300 units/mL (glargine U300) are recognised for their peakless pharmacodynamic profiles, contributing to low variability in glucose-lowering effect, compared to insulin glargine 100 units/mL (glargine U100). Contrasting results were observed in two studies comparing degludec and glargine U300 for within-day glucose variability. It can, however, be expected that the distinct pharmacodynamic profiles of these insulins differentially influence their clinical profiles and the risk of hypoglycaemia.
Participants were randomised 1:1 to degludec U200 or glargine U300.
Key inclusion criteria included ≥18 years old with type 2 diabetes, HbA1c ≤9.5%, BMI ≤45 kg/m2 and treatment with basal insulin with or without any combination of metformin, DPP-4 inhibitors, α-glucosidase inhibitors, thiazolidinediones and SGLT-2 inhibitors at stable doses ≥90 days prior to screening.
A 16-week titration period was followed by a 36-week maintenance period.
Total patients randomised: 1609.
Degludec U200 (n = 805).
Glargine U300 (n = 804).
Primary outcome measure
The primary endpoint was the number of severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during the maintenance period.
During the maintenance period, there was no significant difference in overall hypoglycemic events, which were 40.6% with degludec versus 46.3% with glargine U300 (rate ratio, 0.88; P = 0.17)
Glargine U300 was associated with significantly more severe hypoglycaemic events than degludec U200 (RR 0.20; 95% CI 0.07-0.57; P = 0.0027), but not the number of overall symptomatic episodes (RR 0.88; 95% CI 0.73-1.06; P = 0.17).
Post-hoc analyses showed lower HbA1c and fasting plasma glucose levels at the end of treatment for degludec U200 and less weight gain for glargine U300.
Lower doses were used for degludec U200 compared to glargine U300.
There were no differences in hypoglycaemia during the titration period, and no differences in the overall safety profiles.