In insulin-naive T2D, fixed-dose weekly efsitora was noninferior to daily glargine for reducing HbA1c at 52 wk
Efsitora, a weekly insulin, was associated with weight gain in the industry-funded trial, but for patients with inadequate glycemic control on combination therapy for type 2 diabetes (T2D), weekly insulin will likely provide benefits, an ACP Journal Club commentary said.
Once-weekly efsitora was noninferior to once-daily glargine in reducing HbA1c levels in patients with type 2 diabetes (T2D) who had not previously received insulin therapy, the QUINT-1 trial found. The 52-week, phase 3, open-label trial included 795 participants and found that their mean HbA1c level decreased from 8.20% at baseline to 7.05% with weekly insulin versus from 8.28% to 7.08% with glargine. It was funded by Eli Lilly.
The study was published by the New England Journal of Medicine on June 22. The following commentary by Michael Tanner, MD, MA, FACP, was published in the ACP Journal Club section of Annals of Internal Medicine on Oct. 7.
The novel once-weekly insulin analogues efsitora and icodec have been a long time coming. Insulin glargine, the first once-daily formulation, was approved by the U.S. Food and Drug Administration in 2000. Now, 25 years later, once-weekly insulin has finally been assessed in phase 3 trials.
The QWINT-1 trial by Rosenstock and colleagues showed that weekly efsitora was noninferior to daily glargine for reducing HbA1c levels without increasing risk for hypoglycemia. The simple fixed-dose 100-150-250-400 unit titration approach used in the trial, which is standard administration with weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), can facilitate and mitigate the complex and potentially daunting need to titrate basal insulin using multiple small dose adjustments.
Both the efsitora and glargine groups experienced modest weight gain over the 52-week trial (mean, 3.9 vs. 3.3 kg). Weight gain from insulin is one of the reasons why the 2020 American Diabetes Association standards of care stated that, in most cases, GLP-1 RAs, not insulin, should be used as the first-line injectable medication in T2D.
Weekly insulin has the potential to reduce the injection burden of basal insulin by 86%. The reduction is less in patients with advanced T2D who require basal-bolus insulin, with its substantial treatment burden of 4 injections and 3 finger sticks per day. But for patients with inadequate glycemic control on combination therapy with metformin, a sodium–glucose cotransporter-2 inhibitor, and a GLP-1 RA, adding weekly, instead of daily, insulin is a genuine improvement and having only 4 fixed-dose insulin options can simplify insulin therapy even further.