Continuous Glucose Monitoring-Based Titration of Once-Weekly Insulin Icodec in Insulin-Naive Individuals with Type 2 Diabetes (ONWARDS 9): A Phase 3b, Multicenter, Single-Arm, Treat-to-Target Clinical Trial.

Background: ONWARDS 9 explored, for the first time, the effect of continuous glucose monitoring (CGM)-based titration of once-weekly insulin icodec (icodec) on glycemic control and safety outcomes in individuals with type 2 diabetes (T2D). Methods: In this 26-week, multicenter, single-arm, treat-to-target, phase 3b trial, insulin-naive adults with T2D (glycated hemoglobin [HbA1c] 7.0%-11.0%) initiated icodec at a starting dose of 70 U/week. Participants were provided with an intermittently scanned CGM device, and icodec doses were titrated weekly based on pre-breakfast CGM values (target: 80-130 mg/dL). The primary endpoint was change in HbA1c from week 0 to week 26. Exploratory endpoints included the percentage of time in range (TIR; 70-180 mg/dL), time above range (TAR; >180 mg/dL), and time below range (TBR; <54 mg/dL) from week 22 to week 26. Safety outcomes, including the number of hypoglycemia episodes, were assessed. Results: Of 58 participants screened, 51 received icodec treatment. HbA1c decreased from an observed mean of 8.18% at week 0 to an estimated mean of 7.00% at week 26. There was a statistically significant reduction in HbA1c of -1.17%-points (95% confidence interval: -1.36; -0.99, P < 0.0001). From week -2 to 0 to week 22-26, a concomitant clinically meaningful increase in TIR (54.4% to 76.4%) and decrease in TAR (45.2% to 22.9%) was observed; TBR remained low throughout the trial (week -2 to 0: 0.03%; week 22-26: 0.04%). No severe hypoglycemic episodes were reported during the trial, and no new safety concerns for icodec were identified. Conclusion: After 26 weeks of treatment with icodec titrated based on CGM data, there was a statistically significant reduction in HbA1c from baseline, and the internationally recommended CGM targets for TIR, TAR >180 mg/dL, and TBR <54 mg/dL were achieved. These findings suggest that CGM-based titration of icodec is a feasible method for initiating insulin therapy in T2D. Trial registration: ClinicalTrials.gov identifiers: NCT05823948.