Background: There is a need to validate time-in-range (TIR; percentage of time with plasma glucose between 70 and 180 mg/dL (3.9-10.0 mmol/L) as a surrogate endpoint for long-term clinical outcomes.

Methods: We used data from patients with 8-point glucose profiles (8pp) from the double-blind cardiovascular outcomes trial, DEVOTE (NCT01959529). In total, 7637 patients with T2D and either established CVD or at high risk for CVD were included in the trial. The primary endpoint in DEVOTE was time to first MACE. The 8pp were collected at 1 year, 2 years and end-of-trial. Median length of follow-up was 2 years. For 5644 patients, 8pps with at least 7 points existed. Among the 681 major adverse cardiovascular events (MACEs) in DEVOTE, 360 were among patients with 8pps. Individual TIR was derived as the proportion of the 8pp within range. A Cox model was used to estimate the association between derived TIR and time to first MACE. Hazard ratios (HR) were estimated for patients with TIR>70% vs. TIR≤70%, and for TIR>70% and TIR 50 −70% vs. TIR≤50%.

Results: Derived TIR was >70% for 65% of the patients. Estimated rate of first MACE was lower for TIR >70% and TIR 50-70% vs. TIR≤50% (Figure) and for TIR>70% vs. TIR≤70% (HR: 0.74 [0.60;0.91]95% CI; p<0.01). The associations were maintained when analyses were adjusted for baseline characteristics.

Conclusions: Derived TIR was associated with rate of first MACE for T2D patients in DEVOTE.


R.M. Bergenstal: Consultant; Self; Ascensia Diabetes Care, Johnson & Johnson. Other Relationship; Self; Abbott, Dexcom, Inc., Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Onduo, Roche Diabetes Care, Sanofi, UnitedHealth Group. E. Hachmann-Nielsen: Employee; Self; Novo Nordisk A/S. K. Kvist: Employee; Self; Novo Nordisk A/S. J.B. Buse: Consultant; Self; Cirius Therapeutics, CSL Behring, Neurimmune. Research Support; Self; American Diabetes Association, National Institutes of Health, Novo Nordisk A/S, Patient-Centered Outcomes Research Institute, Sanofi, Tolerion, Inc., vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings, Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg Therapeutics, Novo Nordisk A/S, Senseonics, Inc, vTv Therapeutics, Zafgen, Inc.


Novo Nordisk A/S

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