In this post-hoc meta-analysis, we examined whether severe hypoglycemia impacts HRQoL in insulin-treated patients with type 1 (T1D) and type 2 diabetes (T2D). All open-label, randomized, treat-to-target phase 3a trials (26 or 52 weeks) in which once-daily insulin degludec and insulin glargine were given and HRQoL recorded (T1D: 1 trial; T2D: 5 trials) were eligible for inclusion. Severe hypoglycemia was defined as episodes requiring assistance. HRQoL was assessed at baseline and end of trial via the Short Form 36 (SF-36; v2) questionnaire. Scores for patients who experienced 1 or more episodes of severe hypoglycemia and those who experienced no severe hypoglycemia were compared using ANCOVA. 11.9% (74/621) of T1D patients had at least 1 episode of severe hypoglycemia vs. 1.7% (57/3346) of T2D patients. For both T1D and T2D, patients reporting severe hypoglycemia had a significantly lower (worse) social functioning score (Table). Severe hypoglycemia was also associated with a significantly lower role-physical score in T1D (borderline significant in T2D), and mental health and general health scores in T2D. All other SF-36 scores were lower for patients with severe hypoglycemia (not significant). In conclusion, severe hypoglycemia had a pronounced negative impact on multiple domains of SF-36 in insulin-treated patients with T1D and T2D. These findings highlight the need to minimize hypoglycemia in all forms of diabetes.TableTreatment contrastTreatment contrastSubdomainT1DT2DSubdomainT1DT2DPhysical functioning–0.80 [–2.35; 0.74]–1.18 [–3.37; 1.01]Vitality–0.78 [–2.74; 1.18]–1.12 [–3.36; 1.13]Role-physical–2.16 [–3.88; –0.44]∗–2.19 [–4.39; 0.00]Social functioning–2.30 [–4.27; –0.34]∗–2.69 [–4.99; –0.38]∗Bodily pain–0.86 [–3.15; 1.43]–0.73 [–3.26; 1.79]Role-emotional–0.26 [–2.33; 1.82]–0.92 [–3.54; 1.70]General health–1.60 [–3.41; 0.20]–2.65 [–4.61; –0.70]∗Mental health–1.07 [–3.10; 0.96]–2.39 [–4.73; –0.05]∗Physical component summary–1.51 [–3.04; 0.02]–1.52 [–3.38; 0.33]Mental component summary–0.81 [–2.93; 1.31]–1.74 [–4.05; 0.58]Treatment contrast: patients experiencing severe hypoglycemia–patients who did not experience severe hypoglycemia.∗ p<0.05% Open table in a new tab Treatment contrast: patients experiencing severe hypoglycemia–patients who did not experience severe hypoglycemia. ∗ p<0.05%