medwireNews: The CONCLUDE trial has demonstrated similar overall rates of symptomatic hypoglycemia among type 2 diabetes patients treated with insulin degludec U200 or insulin glargine U300.
In the phase III study, reported at the 55th EASD Annual Meeting in Barcelona, Spain, 1609 adult patients with type 2 diabetes and an inadequate response to basal insulin with or without oral antidiabetic agents were randomly assigned to receive one of two long-acting basal insulins – degludec U200 or glargine U300 – administered in the morning or evening.
Athena Philis-Tsimikas (Scripps Health, San Diego, California, USA) told delegates that following a 16-week titration period, in which the degludec U200 dose was reduced by 20% and glargine U300 was titrated according to the label, patients entered a 36-week maintenance period. However, she noted that the protocol was amended to include an additional 36-week maintenance period due to errors with blood glucose measurement in the original one, meaning that the overall maintenance period was variable, lasting up to 88 weeks.
Athena Philis-Tsimikas discusses which patients may benefit the most from treatment with long-acting insulins, and how the data from CONCLUDE compare with real-world study findings (2:38).
In their analysis of the primary endpoint, the investigators found that overall rates of severe or blood glucose-confirmed symptomatic hypoglycemia during the maintenance period were comparable in the degludec U200 and glargine U300 groups, at 40.6% and 46.3%, respectively.
Philis-Tsimikas said that although the primary endpoint of the study was not met, a number of secondary endpoints occurred at significantly lower rates in the maintenance period among patients treated with degludec U200 compared with glargine U300, including nocturnal symptomatic hypoglycemia (17.8 vs 24.8%) and severe hypoglycemia requiring third-party assistance (0.5 vs 2.7%).
Commenting on these findings, Stefano Del Prato (University of Pisa, Italy) emphasized that “secondary outcomes should be interpreted through the primary outcome,” and if the primary outcome is neutral, as was the case in the CONLCUDE trial, then “all additional outcomes remain exploratory.”
He highlighted the limitations of the study, as acknowledged by Philis-Tsimikas, including the protocol amendment leading to “added complexity,” unknown confounding factors that may have biased investigators’ and participants’ perceptions, and limited generalizability to routine clinical practice.
“Too many uncertainties prevent [us] from drawing firm conclusions from the CONCLUDE trial,” he said.
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EASD 2019; Barcelona, Spain: 16–20 September