Insulin Efsitora a Useful Addition to Treatment of Type 2 Diabetes but not Type 1 Diabetes

Abstract

Efsitora is a once-weekly basal insulin under investigation in a series of 5 phase 3 clinical trials called the QWINT development program. In QWINT-2 and QWINT-5 trials including insulin-naïve patients with type 2 diabetes and adults with type 1 diabetes, respectively, efsitora was compared to once-daily degludec. In both trials, efsitora was found non inferior to degludec in lowering glycated hemoglobin (HbA1c) levels after 52 weeks. In patients with type 2 diabetes, 6 episodes of level 3 hypoglycemia (i.e.  severe hypoglycemia associated with cognitive impairment) occurred with degludec versus none with efsitora. However, incidence of level 1 hypoglycemia or hypoglycemia alert [blood glucose (BG) 54-69 mg/dl] was numerically greater with efsitora versus degludec, estimated rate ratio (ERR) 1.24 (95% CI, 0.99-1.55). Moreover, rates of level 2 hypoglycemia or clinically significant hypoglycemia (BG <54 mg/dl) were also numerically increased with efsitora versus degludec, ERR 1.34 (0.94-1.78). In type 1 diabetes, the QWINT-5 study showed that incidence of all levels of hypoglycemia was significantly increased with efsitora versus degludec, with relative rates of 1.15 (95% CI, 1.03-1.29; P=0.016) and 3.44 (95% CI, 1.64-7.19; P=0.0011) for levels 1 and 3 hypoglycemia, respectively. Incidence of nocturnal hypoglycemia was similar in efsitora and degludec groups in both QWINT-2 and QWINT-5 trials. Patients’ satisfaction was significantly improved with efsitora versus degludec in patients with type 1 and type 2 diabetes. In conclusion, efsitora might be a convenient basal insulin for patients with type 2 diabetes to decrease number of insulin injections. However, efsitora may be unsafe in patients with type 1 diabetes due to increased risk of hypoglycemia. Further studies are required to determine a safe dose-titration strategy to decrease incidence of hypoglycemia with efsitora.