J Diabetes Investig. 2022;13(1):85-93.

Low fasting glucose-to-estimated average glucose ratio was associated with superior response to insulin degludec/aspart compared with basal insulin in patients with type 2 diabetes.

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제1저자 장한나 · 교신저자 정혜승

PMID 34291584 PMC8756314 DOI 10.1111/jdi.13634 IF 3.6 내분비대사내과

소속 (3)

Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.

Abstract

AIMS/INTRODUCTION The benefits of once-daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established.

MATERIALS AND METHODS This was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once-daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated.

RESULTS The IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C-peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P < 0.001). Considering that the lower FPG despite the comparable HbA1c could be related with the efficacy of IDegAsp, subgroup analysis was carried out according to a ratio of FPG-to-estimated average glucose, which is calculated from HbA1c. When compared with each control group, the superiority of IDegAsp in the reduction of HbA1c was significant only in the patients with a lower FPG-to-estimated average glucose ratio (0.49 ± 0.09), but not in those with a higher FPG-to-estimated average glucose ratio (0.79 ± 0.20).

CONCLUSIONS We observed that IDegAsp was more effective than basal insulin in patients with an FPG lower than predicted by HbA1c, which might be related with insulin deficiency and postprandial hyperglycemia in patients on basal insulin therapy.

Keywords

Diabetes mellitus, type 2Insulin degludec/insulin aspartPostprandial hyperglycemia

Figures

**Figure 1** Study population. eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; HTN, hypertension; IDegAsp, insulin degludec/aspart; OAD, oral antidiabetic drug; PP2, 2‐h postprandial glucose; T1DM, type 1 diabetes mellitus.

**Figure 2** Changes in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) during the study period. Among patients with type 2 diabetes receiving basal insulin treatment, those who switched to once‐daily insulin degludec/aspart (IDegAsp) were enrolled. A control group was set by propensity score matching among those who maintained basal insulin. HbA1c and FPG (a) before and (c) after the switch, and (b, d) the changes during the period were compared between the groups by a Student's t‐test. Data are (a, c) means and the standard error of the mean, and (b, d) medians and the ranges (5–95%). *P < 0.05 between the IDegAsp and the control at each time point. ∮P < 0.05 between the IDegAsp and the control. NS, no statistical difference.

**Figure 3** Changes in glycated hemoglobin (HbA1c) in the subgroups according to fasting plasma glucose (FPG)‐to‐estimated average glucose (eAG) ratios. As the baseline and 6‐month FPG were significantly different between the groups, we hypothesized that the discrepancy between FPG and HbA1c would be related with the insulin degludec/aspart (IDegAsp) efficacy. Therefore, the IDegAsp group was divided according to the FPG‐to‐eAG ratio, where eAG was calculated from HbA1c. Then each control was set by propensity score matching, including baseline FPG. (a, b) The FPG‐to‐eAG ratio was lower than 0.6. (c,d) The FPG‐to‐eAG was ≥0.6. HbA1c before and after the switch were analyzed by a paired t‐test, and the changes during the period were compared between the groups by Student’s t‐test and Mann–Whitney U‐test. Data are the (a) means and the (c) standard error of the mean, and (b) medians and (d) the ranges (5–95%). *P < 0.05 between baseline and after 6 months within each group. ∮P < 0.05 between the IDegAsp and the control. NS, no statistical difference.

**Figure 4** A linear regression analysis between baseline glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). A scattered graph showing FPG and HbA1c in the basal insulin cohort (n = 324). Linear regression analysis showed a significant correlation.

그림 출처: PubMed Central 공개 논문 (PMC8756314)

Conflict of interest statement

Hye Seung Jung received a research fund from Novo Nordisk. The other authors declare no conflict of interest.

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