Insulin Degludec / Insulin Aspart

Background: We aimed to confirm that once-daily insulin degludec/insulin aspart (IDegAsp) is superior to basal insulin therapy in participants with type 2 diabetes mellitus (T2DM) exhibiting signs of overbasalization. Additionally, we analyzed incretin profiles in relation to the benefits of IDegAsp, providing insights into the underlying mechanisms.Methods: A prospective study was conducted in participants receiving basal insulin therapy, with a fasting plasma glucose (FPG) level lower than predicted from their glycosylated hemoglobin (HbA1c). Participants were randomly assigned to either IDegAsp or insulin glargine (IGlar) in a 1:1 ratio. After 20 weeks of treatment, the insulins were switched in a crossover design. The primary endpoint was the change in HbA1c from baseline. Incretin profiles, hypoglycemic events, and continuous glucose monitoring (CGM) were also analyzed (Trial registration: www.cris.nih.go.kr; KCT0004597).Results: The study included 55 participants (male 40%, mean age 65 years, FPG 103 mg/dL, and HbA1c 8.3%). HbA1c significantly decreased to 7.8%±0.8% with IDegAsp, compared to 8.0%±0.7% with IGlar. The mean estimated treatment difference of changes was –0.21% points (95% confidence interval, –0.39 to –0.02; P=0.031), favoring IDegAsp. Hypoglycemic events were comparable. CGM demonstrated significantly lower glucose measures during the daytime with IDegAsp compared to IGlar, and vice versa at dawn. The HbA1c benefit of IDegAsp over IGlar was associated with a low glucagon-like peptide-1 (GLP-1) ratio at 30 minutes relative to baseline (r=0.301, P=0.040), while not with glucose-dependent insulinotropic polypeptide.Conclusion: The greater reduction in HbA1c achieved with IDegAsp compared to IGlar in individuals with T2DM was associated with an impaired GLP-1 response, facilitating personalized insulin therapy.

To compare the efficacy and safety of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by β‐cell function in exploratory analyses of the Soli‐D study.

Soli‐D was a 24‐week, multicentre, randomised, open‐label study in Chinese adults with uncontrolled type 2 diabetes (T2D) on oral antidiabetic drugs (OADs). We evaluated glycaemic efficacy, body weight, total insulin daily dose and hypoglycaemia outcomes with iGlarLixi versus IDegAsp by baseline fasting C‐peptide and Homeostasis Model Assessment of β‐cell function (HOMA‐β) quartile measurements.

Among 386 participants, change in glycated haemoglobin (HbA1c), fasting plasma glucose or postprandial glucose at Week 24 showed no interaction with fasting C‐peptide or HOMA‐β quartile. The difference in HbA1c change favoured iGlarLixi versus IDegAsp in fasting C‐peptide quartile 1 (Q1; p  = 0.045) and Q2 ( p  = 0.023) and HOMA‐β Q1 ( p  = 0.025). The proportion of participants with HbA1c <7.0% (<53 mmol/mol) was higher with iGlarLixi in fasting C‐peptide Q2 ( p  = 0.009) and HOMA‐β Q1 ( p  = 0.013). Body weight benefits were observed with iGlarLixi in HOMA‐β Q1 ( p  = 0.003). Total insulin daily dose was lower with iGlarLixi, showing interactions between C‐peptide or HOMA‐β quartile and insulin dose (U or U/kg; pint  <0.001 for all). The event rate for any hypoglycaemia and American Diabetes Association Level 1 hypoglycaemia was lower with iGlarLixi in HOMA‐β Q1 ( p  = 0.040 and 0.037).

iGlarLixi provides improved glycaemic control at lower insulin daily doses compared with IDegAsp, regardless of C‐peptide or HOMA‐β levels, in Chinese people with uncontrolled T2D on OADs.