Efficacy and Safety of Insulin Efsitora Versus Degludec in Adults with Type 2 Diabetes Who Are Insulin-Naïve: Japan Subgroup Analysis of QWINT-2

The phase 3 QWINT-2 study demonstrated that once-weekly insulin efsitora alfa (efsitora) was noninferior to once-daily insulin degludec (degludec) in reducing glycated hemoglobin (HbA1c) at week 52 when added to existing noninsulin glucose-lowering agents in adults with type 2 diabetes who were insulin-naïve. A Japan subgroup analysis of QWINT-2 using two dosing algorithms is presented here. Participants from Japan were randomized 1:1 to efsitora or degludec and followed one of two dosing algorithms: a general dosing algorithm or an optional alternative dosing algorithm available for participants anticipated to require less insulin, characterized by a body weight ≤ 60 kg or HbA1c level ≤ 7.5% at baseline. Assessments included changes in HbA1c and fasting blood glucose from weeks 0–52, time spent in target glucose range (TIR) from weeks 48–52, and hypoglycemia from weeks 0–52. In total, 144 participants from Japan were included (efsitora, n = 71; degludec, n = 73). Demographic and baseline characteristics were generally balanced between treatment groups. From weeks 0–52, mean HbA1c decreased from 8.04% to 6.63% with efsitora and from 8.00% to 6.64% with degludec (estimated treatment difference, −0.01%). TIR was similar between efsitora and degludec from weeks 48–52. Rates of combined level 2 or 3 hypoglycemia were low overall (weeks 0–52) and during the initial dosing period (weeks 0–12). Level 3 hypoglycemia was not reported in any participants with efsitora and two participants with degludec. The incidence of adverse events was similar between efsitora and degludec. The efficacy and safety of efsitora were comparable with degludec using the general and alternative dosing algorithms in Japanese participants. Once-weekly efsitora was comparable to once-daily degludec in reducing HbA1c in Japanese participants who were insulin-naïve. The efficacy and safety of efsitora in Japanese participants were consistent with the overall QWINT-2 study population. NCT05362058. Japanese people with type 2 diabetes tend to have a lower body mass index and less impairment of the effects of insulin than Western people. Thus, they require less insulin to achieve comparable reductions in blood sugar. This study looked at Japanese participants who had not used insulin before in a clinical trial called QWINT-2. This trial compared two types of insulin: (1) efsitora, a new insulin taken once a week, and (2) degludec, a widely used insulin taken once a day. Some participants received a lower dose of insulin efsitora or degludec if they weighed 60 kg or less or had relatively good blood sugar control (blood sugar less than or equal to 7.5%). Once-weekly insulin (efsitora) worked just as well and was just as safe as once-daily insulin (degludec) in Japanese people with type 2 diabetes. This was true regardless of which of the two different methods was used to optimize the insulin dose. These results were also similar to those seen in the overall QWINT-2 trial. This study shows that once-weekly insulin efsitora could help people, including Japanese people, with type 2 diabetes initiate and continue insulin treatment. The study also shows that adjusting insulin doses on the basis of individual factors—such as body mass index or blood sugar levels—has benefit for some Japanese people.