The successful management of diabetes relies on regulating short-term glucose variations to achieve long-term glycemic goals, typically measured by glycated hemoglobin (HbA1c). HbA1c provides a 3-month average of glucose exposure and has been correlated with risk of developing diabetes complications.1 To achieve HbA1c targets, both fasting plasma glucose (FPG) and postprandial glucose (PPG) need to be considered, an interrelationship known as the glucose triad.2 Previous studies have shown that increased FPG and PPG contribute to elevated HbA1c.3,4 However, there are limited reports on the effectiveness of treatments that aim to specifically manage FPG and PPG, particularly among those who require basal-bolus insulin treatment.

Time in range (TIR) is an increasingly recognized measure of glycemic management that complements HbA1c and enables daily monitoring of glucose levels. TIR is defined as the time spent in the glucose range between 70 and 180 mg/dL (3.9–10.0 mmol/L). Reduced TIR has been associated with increased risk of diabetes-related complications and higher HbA1c.5., 6., 7. The rise in the use of continuous glucose monitoring (CGM) has allowed for more frequent and precise measurement of TIR and of PPG and FPG, enabling clinicians to target areas for improvement in the individualized management of diabetes.8 It is important to investigate how these metrics are related with each other and with HbA1c to best leverage them in the management of diabetes, especially with the development of innovative insulins such as new rapid acting insulin analogues that further improve FPG and PPG.

Recently, a pooled analysis of insulin lispro (Humalog®) clinical trials in people with type 2 diabetes (T2D) found that reductions in both FPG and PPG were significantly associated with decreased HbA1c and increased TIR.9 The current study extends analysis to people with type 1 diabetes (T1D) or T2D treated with lispro or a new insulin lispro formulation, ultra rapid lispro (URLi), available as Lyumjev®, which contains locally acting excipients citrate and treprostinil. URLi has been shown to exhibit non-inferior HbA1c control and superior PPG control compared with lispro in patients with T1D10 and T2D.11

Using datasets from the PRONTO-T1D10,12 and PRONTO-T2D11 phase 3 clinical trials, this study evaluated the relationship between changes in FPG and PPG on changes in HbA1c and TIR in people with T1D and T2D treated with URLi or lispro as the bolus insulin in a basal-bolus multiple daily injection (MDI) regimen. Additionally, we analyzed the impact of FPG and PPG on TIR derived from both CGM12 as well as from self-monitored blood glucose (SMBG),10,11 and the relationship between CGM-derived TIR and HbA1c.12