• Julio Rosenstock, Stephen C Bain, Amoolya Gowda, Esteban Jódar, Bo Liang, Ildiko Lingvay, Tomoyuki Nishida, Roberto Trevisan, Ofri Mosenzon, and ONWARDS 1 Trial Investigators.
• From Velocity Clinical Research at Medical City (J.R.) and the Division of Endocrinology, Department of Internal Medicine, and the Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center (I.L.) - both in Dallas; Swansea University Medical School, Swansea, United Kingdom (S.C.B.); Novo Nordisk, Søborg, Denmark (A.G., B.L.); Servicio de Endocrinología y Nutrición, Hospital Universitario Quironsalud Madrid, Facultad de Medicina, Universidad Europea, Madrid (E.J.); Novo Nordisk, Tokyo (T.N.); Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (R.T.), and the Department of Medicine and Surgery, University of Milano Bicocca, Milan (R.T.) - both in Italy; and the Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center (O.M.), and the Faculty of Medicine, Hebrew University of Jerusalem (O.M.) - both in Jerusalem.
• N. Engl. J. Med. 2023 Jul 27; 389 (4): 297308297-308.

BackgroundInsulin icodec is an investigational once-weekly basal insulin analogue for diabetes management.MethodsWe conducted a 78-week randomized, open-label, treat-to-target phase 3a trial (including a 52-week main phase and a 26-week extension phase, plus a 5-week follow-up period) involving adults with type 2 diabetes (glycated hemoglobin level, 7 to 11%) who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive once-weekly insulin icodec or once-daily insulin glargine U100. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; the confirmatory secondary end point was the percentage of time spent in the glycemic range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) in weeks 48 to 52. Hypoglycemic episodes (from baseline to weeks 52 and 83) were recorded.ResultsEach group included 492 participants. Baseline characteristics were similar in the two groups. The mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec than with glargine U100 (from 8.50% to 6.93% with icodec [mean change, -1.55 percentage points] and from 8.44% to 7.12% with glargine U100 [mean change, -1.35 percentage points]); the estimated between-group difference (-0.19 percentage points; 95% confidence interval [CI], -0.36 to -0.03) confirmed the noninferiority (P<0.001) and superiority (P = 0.02) of icodec. The percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec than with glargine U100 (71.9% vs. 66.9%; estimated between-group difference, 4.27 percentage points [95% CI, 1.92 to 6.62]; P<0.001), which confirmed superiority. Rates of combined clinically significant or severe hypoglycemia were 0.30 events per person-year of exposure with icodec and 0.16 events per person-year of exposure with glargine U100 at week 52 (estimated rate ratio, 1.64; 95% CI, 0.98 to 2.75) and 0.30 and 0.16 events per person-year of exposure, respectively, at week 83 (estimated rate ratio, 1.63; 95% CI, 1.02 to 2.61). No new safety signals were identified, and incidences of adverse events were similar in the two groups.ConclusionsGlycemic control was significantly better with once-weekly insulin icodec than with once-daily insulin glargine U100. (Funded by Novo Nordisk; ONWARDS 1 ClinicalTrials.gov number, NCT04460885.).Copyright © 2023 Massachusetts Medical Society.

37 keywords...

hide…