Reducing glycemic fluctuation is important for optimal diabetes management. (HbA1c) levels and reducing glycemic fluctuations to achieve a balance between glycemic control and avoidance of hypoglycemia.1,2 Unfortunately, patients with an acceptable HbA1c level may still experience significant glycemic fluctuation over a 24-h period.3 There is evidence that glycemic fluctuation is an independent risk factor for diabetic complications,4,5 predictive of hypoglycemia,6 and when manifesting as postprandial hyperglycemia may contribute to vascular complications. 7C9 Despite some controversy on these issues,10,11 reducing glycemic fluctuation is important for optimal glycemic control,4 and treatments that offer reductions in both HbA1c and glycemic fluctuation are desirable. IDegLira, a fixed ratio combination of insulin degludec (IDeg), a long-acting basal insulin, and the glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, has demonstrated significantly greater reductions in HbA1c compared to the individual components liraglutide and IDeg alone.12C15 IDegLira has also been shown to have favorable effects on body weight and reduced risk of hypoglycemia compared to IDeg alone.12C15 219911-35-0 These observations are likely explained by the complementary mode of action of the two components of IDegLira, namely the ability of IDeg to 219911-35-0 reduce fasting plasma glucose16 and the glucose-dependent effects of liraglutide, both lowers fasting plasma glucose and reduces postprandial glucose excursions.17 The objective of this post hoc analysis was to use self-monitored blood glucose (SMBG) and continuous glucose monitoring (CGM) to determine whether or not IDegLira would bring more patients with type 2 diabetes (T2D) within blood glucose target ranges, compared to its individual components. In this article, we describe glycemic fluctuation from a patient’s average blood glucose values and explore day-to-day variability by comparing the standard deviation (SD) of consecutive blood glucose concentrations. Materials and Methods DUAL I extension and DUAL II study overviews This post hoc analysis used data from the DUAL I extension and DUAL II trials in patients with T2D; detailed trial designs and methods were reported previously.13C15 Briefly, DUAL I was a 26-week trial14 with an extension to MRC1 52 weeks15 comparing IDegLira with IDeg or liraglutide in insulin-na?ve patients uncontrolled on oral antidiabetic drugs (OADs; in this case being metformin with or without pioglitazone). Throughout this article, when referring to DUAL I, results from the full 52-week trial are reported. In 219911-35-0 DUAL II, IDegLira was compared with IDeg for 26 weeks in patients who were previously uncontrolled on 20 to 40?U of basal insulin plus metformin, with or without sulfonylureas or glinides; these latter two classes were discontinued at randomization.13 In DUAL II, IDeg was limited to a maximum dose of 50?U so that the contribution of the liraglutide component of IDegLira could be evaluated at equivalent insulin doses. The trial protocols were approved by independent ethics committees or institutional review boards at all participating institutions and conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.18,19 Written informed consent from all patients was obtained before enrollment. The baseline characteristics of the patients in the two trials are summarized in the Supplementary Tables S1 and S2 (Supplementary Data are available online at www.liebertpub.com/dia). SMBG profiles SMBG levels were assessed in the DUAL I extension and DUAL II trials using hand-held glucose meters (Abbott Diabetes Care, Alameda) calibrated to display plasma equivalent values of capillary whole blood glucose measurements. SMBG levels were recorded in the diary in the following sequence of time points: (1) just before breakfast; (2) 90?min after the start of breakfast; (3) just before lunch; (4) 90?min after the start of lunch; (5) just before dinner; (6) 90?min after the start of dinner; (7) at bedtime; (8) at 4?am; and (9) just before breakfast the following day. These nine-point profiles were completed within 1 week before site visits on a day when the subject did not anticipate unusual strenuous exercise. The 90-min postprandial interval was selected 219911-35-0 as the mid-point in the 1C2?h timeframe recommended for assessing postprandial plasma glucose targets, and in an effort to provide a closer reflection of postprandial peak than the common 2-h postprandial interval.4,20 In addition, fasting prebreakfast SMBG was measured daily for both IDeg and IDegLira treated patients (the two study arms that included dose titration), and 3 days a week for liraglutide-treated patients (as per study protocol). Interpreting nine-point SMBG profiles We assessed the proportions of patients treated with IDegLira, IDeg, or liraglutide, who achieved SMBG values (plasma.