MDI users with type 1 diabetes may be less able to respond to circadian changes in insulin demand than CSII or AID users, which may increase the risk of nocturnal hypoglycemia. Therefore, we re-analyzed data from the HYPO.DE RCT to evaluate the effect of CGM on the percentage of low glucose levels < 70 mg/dl (% < 70 mg/dl) and < 54 mg/dl (% < 54 mg/dl) during 12 two-hour periods throughout the day. We compared 4-week baseline data from 141 participants using spot glucose monitoring (SMBG) with 4-week outcome data after a 6-month follow-up period in which the control group (n=66) remained on SMBG and the intervention group (n=75) used CGM (Dexcom G5). At baseline without CGM, there were significantly higher proportions of %<70 mg/dl or %54 mg/dl during the night (00:00 am - 06:00 am) than during the day (8.5 ±1.0% vs. 6.5 ±0.6%, p<0.001 respectively 4.0 ±0.6% vs. 2.4 ±0.3%, p<0.001). CGM had a greater effect on nocturnal hypoglycemia than on daytime hypoglycemia (see Figure 1). The greatest reduction in favor of the CGM users was between 04:00 a.m. and 06:00 a.m., with a between-group difference of -8.5% (95% CI -10.4% to -6.7%, p<.001) for %<70 mg/dl and -5.5% (95% CI 4.4 - 6.6%, p<.001) for %<54 mg/dl. The data suggest that CGM provides benefits to MDI users with type 1 diabetes in preventing nocturnal hypoglycemia, potentially compensating for lack of responsiveness to a circadian changing insulin demand. Disclosure N. Hermanns: Speaker's Bureau; Berlin-Chemie AG, Sanofi-Aventis Deutschland GmbH. Research Support; Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Roche Diabetes Care. Research Support; Roche Diabetes Care. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Abbott Diagnostics, Ypsomed AG. D. Ehrmann: Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Sanofi-Aventis Deutschland GmbH. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care, Berlin-Chemie AG. B. Kulzer: Advisory Panel; Abbott Diagnostics, Berlin-Chemie AG, Dexcom, Inc., Sanofi, embecta, Novo Nordisk, Roche Diabetes Care. Speaker's Bureau; Bayer Inc., Insulet Corporation, Lilly Diabetes. G. Freckmann: Advisory Panel; Abbott. Research Support; Ascensia Diabetes Care. Advisory Panel; Boydsense, Dexcom, Inc., Lilly Diabetes. Speaker's Bureau; Novo Nordisk. Advisory Panel; Perfood, PharmaSens. Consultant; Roche Diabetes Care. Research Support; Roche Diabetes Care. Consultant; Sinocare. Speaker's Bureau; Terumo Corporation. Consultant; Ypsomed AG. L. Heinemann: Stock/Shareholder; Science Consulting in Diabetes GmbH, Profil Institut für Stoffwechselforschung GmbH. Advisory Panel; embecta. Board Member; Lifecare A/S. Stock/Shareholder; diateam GmbH. Funding The HYPO.DE study was funded by Dexcom, San Diego