Abstract
Aims
To evaluate and compare the effectiveness of once-daily insulin degludec/liraglutide (IDegLira) to that of once-daily insulin degludec/insulin aspart (IDegAsp) after switching from basal insulin therapy at 6 months by assessing changes in hemoglobin A1c (HbA1c), body weight, and insulin doses in patients with type 2 diabetes (T2D).
Materials and methods
A total of 91 patients with T2D with HbA1c levels exceeding 7.0% were included in this study. Adjusted least square mean changes in HbA1c, body weight, and total insulin doses were compared between the IDegLira group and IDegAsp group. Subgroup analyses were performed, stratified by median values of HbA1c (< 8.5 and ≥ 8.5%), obesity (body mass index < 25 and ≥ 25 kg/m2), and basal insulin doses (< 14 and ≥ 14 units) at baseline to assess treatment interaction by subgroup.
Results
The IDegLira group showed a greater reduction in HbA1c levels than the IDegAsp group (− 0.17 vs − 0.79%, p = 0.003) with comparable body weight changes. The analyses of adjusted mean changes of total insulin doses showed that the IDegAsp group had a larger increase than the IDegLira group (3.64 vs 1.30 unis, p = 0.016). The effect of IDegLira on HbA1c levels was superior to that of IDegAsp in patients with high HbA1c. There were no inter-group differences in the rate of hypoglycemic episodes.
Conclusions
Once-daily IDegLira had greater effects on HbA1c and a lesser increase in insulin doses than IDegAsp when patients are switched from basal insulin therapy. Moreover, the effect on HbA1c was enhanced in patients with high HbA1c levels at baseline.
Keywords: Type 2 diabetes, Insulin degludec/liraglutide, Insulin degludec/insulin aspart, HbA1c
Introduction
Optimal glucose control is required in patients with type 2 diabetes (T2D) to reduce the risk of micro- and macrovascular complications. The American Diabetes Association guidelines for the management of T2D recommends the addition of prandial insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs), if patients have high levels of hemoglobin A1c (HbA1c) above the target with basal insulin therapy [1]. However, as several daily injections can be burdensome and as such, can result in poor adherence [2], a simple intensification option is desirable.
Premixed insulin formulations cover both basal and mealtime insulin needs in one injection and are commonly prescribed for Japanese patients with T2D owing to the high carbohydrate content of the Japanese diet [3]. It has been shown that insulin degludec/insulin aspart (IDegAsp; 70% IDeg and 30% IAsp) administered once daily provided superior long-term glycemic control compared to insulin glargine administered once daily, with similar fasting plasma glucose, insulin doses, and comparable weight gain [4].
The availability of fixed-ratio insulin/GLP-1RA combinations in recent times allows for the combination of basal insulin and GLP-1RA to be administered once daily [5]. IDeg/liraglutide (IdegLira; one dose step contains 1unit IDeg and 0.036 mg liraglutide) [6], approved for use in Japan in September 2019, showed superior reductions in HbA1c levels compared to IDeg when patients switched from basal or premixed insulin in the phase 3 trial [7]. Moreover, it has been shown that IDegLira treatment provided non-inferior glycemic control compared to the basal-bolus regimen with lesser total insulin doses and a desirable effect for weight loss in T2D patients uncontrolled on basal insulin therapy [8]. Basal insulin doses at endpoints were approximately 40–50 units in these trials; however, these strict titrations would be difficult in clinical practice owing to concerns of hypoglycemic risk.
There is limited information on the effectiveness of IDegLira when switching from basal insulin therapy in real-world practice [9, 10]. Thus, the purpose of this study was to compare the effectiveness of once-daily IDegLira with that of once-daily IDegAsp in patients with T2D switched from basal insulin therapy in a real-world clinical setting.
Materials and methods
Patient selection
We conducted a single-center retrospective observational study using the electronic medical records of the hospital. Four hundred and ninety-eight patients with T2D with basal insulin therapy, with or without non-insulin glucose lowering agents, except for GLP-1 RA, for at least 6 months were first extracted between June 2019 and December 2021. Then patients with HbA1c levels under 7.0% (n = 49) were excluded. Finally, 99 patients whose their basal insulin regimens were switched from insulin glargine 100 U/mL, insulin glargine 300 U/mL, or IDeg to IDegLira or IDegAsp remained. Patients with missing data on body weight (n = 1), undergoing hemodialysis (n = 2), renal transplantation (n = 1), steroid therapy (n = 2), pancreatic diseases or carcinomas (n = 2), and those who were transferred to another hospital (n = 1) were excluded from this study. The remaining 91 patients were included in the study analysis.
Titration of injection dose was left to the discretion of each physician and adjusted to avoid hypoglycemia.
Measurements
Data on age, sex, anthropometric measurements, duration of diabetes, HbA1c levels, and use of glucose-lowering agents were obtained from the medical records. The index date was defined as the date on which the IDegLira or IDegAsp treatment was initiated. Body mass index (BMI) was calculated as weight divided by height in meters squared (kg/m2). HbA1c values were measured using high-performance liquid chromatography (Adams A1c HA-8160; Arkray, Kyoto, Japan) and were reported as percentages assigned by the National Glycohemoglobin Standardization Program [11]. Patients were asked whether their hypoglycemic symptoms increased after switching to IDegLira or IDegAsp. Data on fasting blood glucose (FBG) levels were collected from patients whose self-monitoring of blood glucose (SMBG) records were available for at least 15 days a month before and after switching.
Outcome measurements
The primary outcomes were changes in HbA1c levels, body weight, and total insulin doses 6 months after switching from other basal insulins to IDegLira or IDegAsp. The secondary outcomes were changes in HbA1c levels, body weight, and total insulin doses stratified by HbA1c levels, BMI, and basal insulin doses at baseline. In addition, the frequency of hypoglycemic episodes (< 70 mg/dl) during a month before and after switching to IDegLira or IDegAsp was examined.
Statistical analysis
Continuous variables are presented as the means and standard deviations or medians and interquartile ranges and were compared using the Mann–Whitney U test. Categorical data are expressed as proportions and were compared using the chi-squared test. The main analysis was conducted on the intention-to-treat population. Analysis of covariance (ANCOVA) was used to calculate the least squares (LS) mean changes in HbA1c, body weight, and total insulin doses between the IDegLira and IDegAsp groups after adjusting for the following covariates: age, sex, HbA1c, basal insulin doses, use of metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors at baseline. Additionally, ANCOVA model analyses were performed to assess interaction between subgroup and treatment groups. Subgroups were stratified by median values of HbA1c levels (< 8.5 and ≥ 8.5%), obesity; BMI (< 25 and ≥ 25 kg/m2), and median values of basal insulin doses (< 14 and ≥ 14 units) at baseline. FBG data from SMBG records were analyzed to evaluate changes in the rate of hypoglycemic episodes before and after switching, using a paired t-test. Incidence of hypoglycemic episodes was compared between groups using multivariate Poisson’s regression model. All statistical analyses were performed using R (version 4.0.5; R Foundation for Statistical Computing, Austria). p-values were based on two-sided tests, and statistical significance was set at p < 0.05.
Ethical considerations
The study was approved by the Ethics Review Committee of Tokyo Women’s Medical University (approval no. 2481-R3, November 18, 2022). All clinical investigations were conducted in accordance with the tenets of the Declaration of Helsinki.
Results
Patient characteristics
The IDegLira group had a later index date, younger age, and higher administration rate of metformin and sodium-glucose cotransporter-2 inhibitors than the IDegAsp group (Table 1). In the IDegAsp group, four patients were not able to continue the therapy because of other diseases (n = 2), hypoglycemic episodes (n = 1), or worsening glucose control (n = 1). Similarly, three patients in the IDegLira group changed their treatment owing to vomiting (n = 1), diarrhea (n = 1), and appetite loss (n = 1).
Table 1.
Baseline characteristics
| IDegAsp | IDegLira | p value | |
|---|---|---|---|
| N | 52 | 39 | |
| Index date, year/month (IQR) | 2020/3 (2019/7–2020/9) | 2021/3 (2020/12–2021/7) | < 0.001 |
| Age, years | 68 ± 12 | 63 ± 13 | 0.024 |
| Sex (men, %) | 71.2 | 69.2 | 1.000 |
| Body weight, kg | 67.5 ± 15.3 | 71.9 ± 12.1 | 0.147 |
| BMI, kg/m2 | 25.2 ± 4.3 | 26.6 ± 4.2 | 0.147 |
| Duration of diabetes, years | 21.5 ± 10.5 | 23.1 ± 10.3 | 0.465 |
| HbA1c, % | 8.7 ± 1.0 | 8.6 ± 1.3 | 0.074 |
| eGFR, mL/min/1.73 m2 | 63.7 ± 23.4 | 64.9 ± 22.2 | 0.529 |
| Previous basal insulin, N (%) | 0.546 | ||
| Glargin100 U/mL | 16 (30.8) | 14 (35.9) | |
| Glargin 300 U/mL | 16 (30.8) | 8 (20.5) | |
| Degludec | 20 (38.4) | 17 (43.6) | |
| Basal insulin dose, units (IQR) | 13 (7–20) | 14 (9–18) | 0.587 |
| Basal insulin dose, units/kg (IQR) | 0.20 (0.11–0.29) | 0.17 (0.13–0.25) | 0.718 |
| Noninsulin antihyperglycemic agents, N (%) | |||
| Metformin | 16 (30.8) | 31 (79.5) | < 0.001 |
| Sulfonylurea | 23 (44.2) | 17 (43.6) | 1.000 |
| DPP-4 inhibitors | 39 (75.0) | 30 (76.9) | 1.000 |
| Thiazolidinediones | 4 (7.7) | 4 (10.3) | 0.957 |
| Glinides | 8 (15.4) | 6 (15.4) | 1.000 |
| α-GIs | 16 (30.8) | 7 (17.9) | 0.251 |
| SGLT2 inhibitors | 22 (42.3) | 26 (66.7) | 0.048 |
| Diabetic retinopathy (none/ simple/ proliferative), N (%) | 10/ 9/ 3 (45.5/ 40.9/ 13.6) | 11/ 7/ 3 (52.4/ 33.3/ 14.3) | 0.872 |
Data are presented as mean ± standard deviation or median (interquartile range (IQR))
IDegAsp, Degludec/Aspart; IDegLira, Degludec/Liraglutide; BMI, body mass index; eGFR, estimated glomerular filtration; DPP-4, dipeptidyl peptidase 4; α-GIs, α-glucosidase inhibitors; SGLT2, sodium-glucose cotransporter 2
Changes in outcomes at 6 months after switching from basal insulin
Table 2 shows characteristics of each group at 6 months after switching from basal insulin therapy. HbA1c and total insulin dose in the IDegLira group were lower than those in the IDegAsp group. In the IDegAsp group, sulfonylurea, dipeptidyl peptidase 4 (DPP4) inhibitors and SGLT2 inhibitors were decreased, while metformin and glinides were increased. In the IDegLira group, sulfonylurea, DPP4 inhibitors and thiazolidinediones were decreased while glinides was increased.
Table 2.
Characteristics of each group 6months after switching
| IDegAsp | IDegLira | p value | |
|---|---|---|---|
| Body weight, kg | 67.6 ± 15.3 | 71.7 ± 12.2 | 0.142 |
| BMI, kg/m2 | 25.3 ± 4.3 | 26.6 ± 4.2 | 0.218 |
| HbA1c, % | 8.5 ± 1.2 | 7.8 ± 0.9 | 0.003 |
| Total insulin dose, units (IQR) | 17 (12–23) | 14 (12–18) | 0.199 |
| Total insulin dose, units/kg (IQR) | 0.24 (0.19–0.33) | 0.21 (0.16–0.25) | 0.023 |
| Noninsulin antihyperglycemic agents, N (%) | |||
| Liraglutide dose, mg (IQR) | 0.50 (0.33–0.65) | ||
| Metformin | 18 (34.6) | 31 (79.5) | < 0.001 |
| Sulfonylurea | 17 (32.7) | 12 (30.8) | 1.000 |
| DPP-4 inhibitors | 36 (69.2) | 1 (2.6) | < 0.001 |
| Thiazolidinediones | 4 (7.7) | 3 (7.7) | 1.000 |
| Glinides | 10 (19.2) | 8 (20.5) | 0.783 |
| α-GIs | 16 (30.8) | 7 (17.9) | 0.251 |
| SGLT2 inhibitors | 21 (40.4) | 26 (66.7) | 0.008 |
Data are presented as mean ± standard deviation or median (interquartile range (IQR))
IDegAsp, Degludec/Aspart; IDegLira: Degludec/Liraglutide; BMI, body mass index; DPP-4, dipeptidyl peptidase 4; α-GIs, α-glucosidase inhibitors; SGLT2, sodium-glucose cotransporter 2
Table 3 shows the LS mean changes in HbA1c levels, body weight, and total insulin doses from baseline for each group. Mean reduction in HbA1c levels 6 months after switching was 0.17% and 0.79% in patients in the IDegAsp and IDegLira groups, respectively. The IDegLira group showed a greater reduction in HbA1c levels than the IDegAsp group (p = 0.003). The IDegAsp group showed a slight gain, while the IDegLira group had a slight reduction in body weight; however, the changes were not significantly different. The analyses of adjusted mean changes in total insulin doses showed that the IDegAsp group had a larger increase than the IDegLira group (p = 0.016).
Table 3.
Comparison of adjusted mean changes of outcomes between IDegAsp and IDegLira at 6 months
| IDegAsp | IDegLira | p value | |
|---|---|---|---|
| HbA1c (%) | − 0.17 (0.13) | − 0.79 (0.15) | 0.003 |
| Body weight (kg) | 0.22 (0.35) | − 0.09 (0.41) | 0.560 |
| Total insulin dose (units) | 3.64 (0.59) | 1.30 (0.70) | 0.016 |
| Total insulin dose (units/kg) | 0.06 (0.01) | 0.02 (0.01) | 0.018 |
Data are presented as least squares mean of change from baseline (standard error)
IDegAsp, Degludec/Aspart; IDegLira, Degludec/Liraglutide
Adjusted for age, sex, HbA1c at baseline, basal insulin dose, use of metformin and SGLT2 inhibitor at baseline
Differences of changes in outcomes stratified by HbA1c, BMI, and insulin dose at baseline
The IDegLira group showed a significantly larger reduction in HbA1c levels than the IDegAsp group in baseline HbA1c ≥ 8.5% subgroup relative to HbA1c < 8.5% subgroup with comparable changes in body weight and insulin dose (Table 4). There was statistically significant treatment-by-subgroup interaction between baseline HbA1c and the change in HbA1c for the IDegLira and the IDegAsp group. There were no significant treatment-by subgroup interactions between baseline HbA1c and the change in body weight and total insulin dose (Table 4). Similarly, there were no statistically significant treatment-by-subgroup interaction between baseline BMI and the change in HbA1c, body weight and total insulin dose (Table 4). The borderline significance was showed in treatment-by subgroup interactions between baseline total insulin dose and the change in body weight but not in change in HbA1c and total insulin dose.
Table 4.
Estimated mean differences of changes in outcomes between IDegAsp and IDegLira at 6months stratified by HbA1c, BMI and basal insulin dose at baseline
| ΔHbA1c (%) and 95%CI | Treatment-by-subgroup interaction | ΔBody weight (kg) and 95% CI | Treatment-by-subgroup interaction | ΔTotal insulin dose (units) and 95%CI | Treatment-by-subgroup interaction | |
|---|---|---|---|---|---|---|
| HbA1c ≥ 8.5% (N: 29/18) | − 0.63 (− 0.02; − 1.25) | 0.030 | − 0.42 (− 1.96; 1.12) | 0.906 | − 2.55 (− 4.70; − 0.40) | 0.832 |
| HbA1c < 8.5% (N: 23/21) | − 0.26 (− 0.66; 0.15) | − 0.34 (− 1.47; 0.79) | − 2.99 (− 5.15; − 0.83) | |||
| BMI ≥ 25 kg/m2 (N: 27/23) | − 0.33 (− 0.80; 0.14) | 0.793 | − 0.13 (− 1.49; 1.22) | 0.495 | − 4.05 (− 5.99; − 2.11) | 0.228 |
| BMI < 25 kg/m2 (N: 25/16) | − 0.45 (− 1.16; 0.27) | − 0.55 (− 1.80; 0.70) | − 1.08 (− 3.44; 1.28) | |||
| Basal insulin dose ≥ 14 U (N: 26/20) | − 0.33 (− 0.90; 0.24) | 0.961 | − 0.57 (− 1.91; 0.77) | 0.050 | − 2.70 (− 4.46; − 0.94) | 0.679 |
| Basal insulin dose < 14 U (N: 26/19) | − 0.42 (− 0.98; 0.13) | − 0.13 (− 1.35; 1.09) | − 2.71 (− 4.98; − 0.43) |
N: IDegAsp/IDegLira
Δ: Difference of change from baseline between IDegLira group and IDegAsp group (IDegLira—IDegAsp)
Data are presented as estimated mean and 95% confidence interval
Adjusted for age, sex, HbA1c at baseline, basal insulin dose, use of metformin and SGLT2 inhibitor at baseline
Hypoglycemia
Patients were asked about the frequency of symptomatic hypoglycemic episodes at every visit before and after switching. Three (5.7%) and two (5.1%) patients in the IDegAsp and IDegLira groups, respectively, had more frequent symptomatic hypoglycemic episodes after switching. There were no significant differences in the frequency of symptomatic hypoglycemia pre- and post-switching between the IDegAsp and IDegLira groups. The frequency of hypoglycemic episodes (< 70 mg/dl) among patients with FBG data available from SMBG records are shown in Table 5. The rate of hypoglycemic episodes remained unchanged across both groups. No between-group differences emerged.
Table 5.
Change of frequency of hypoglycemic episodes
| Episodes | IR (95% CI) | IRR (95% CI) | p value | Between-group p-value | ||
|---|---|---|---|---|---|---|
| IDegAsp (N = 33) | Baseline (− 1 to 0 month) | 11 | 0.34 (0.20; 0.52) | |||
| 6 months (6 to 7 months) | 9 | 0.39 (0.22; 0.59) | 0.813 | |||
| IDegLira (N = 24) | Baseline (− 1 to 0 month) | 13 | 0.40 (0.25; 0.57) | |||
| 6 months (6 to 7 months) | 9 | 0.39 (0.22; 0.59) | 0.42 (0.16; 1.09) | 1.000 | 0.543 |
IDegAsp, Degludec/Aspart; IDegLira, Degludec/Liraglutide
IR: incident rate of hypoglycemic episodes per patient-month of exposure, 95% CI: 95% confidence interval
IRR: incident rate ratio
Discussion
The present study showed that the 6-month reduction in HbA1c levels was greater in the IDegLira group, whose basal insulins were switched to once-daily IDegLira, than that in the IDegAsp group, whose basal insulins were switched to once-daily IDegAsp. The increase in total insulin dose was lower in the IDegLira group than that in the IDegAsp group, with body weight remaining almost unchanged in both groups. The IDegLira group had a greater effect on HbA1c levels than the IDegAsp group in patients with high HbA1c levels. Similarly, the IDegLira group had a greater body weight reduction than the IDegAsp group in patients with high basal insulin dose at baseline. To the best of our knowledge, this is the first study to compare the effectiveness of IDegLira and IDegAsp on glycemic control, body weight, and insulin doses when switching from basal insulin therapy in real-world clinical settings.
A previous report suggested that combination therapy with GLP-1RA and insulin provided antihyperglycemic efficacy similar to that of basal-plus or basal-bolus therapy [12]. However, an increase in the number of injections was related to poor adherence [13]. Once-daily IDegLira showed high persistence [14], whereas the GLP-1RA dose was lower than that of GLP-1RAs in free combination with insulin. The DuUal Action of Liraglutide and insulin degludec in type 2 diabetes (DUAL) II Japan trial [7] showed a superior reduction in HbA1c levels compared to IDeg when switching from basal or premixed insulin. Additionally, the DUAL VII trial [8] reported that IDegLira provided non-inferior glycemic control compared to the basal-bolus regimen. The dose steps at the end of these trials were approximately 40 doses that contained 1.4 mg of liraglutide. In real-world clinical practice, insulin doses would be lower than that in clinical trials, as in this study, in which the median dose was 14 doses with 0.5 mg liraglutide. IDegAsp has been widely used as a next step in patients with uncontrolled basal insulin therapy. Once-daily IDegAsp showed superior long-term glycemic control compared to once-daily insulin glargine [4], and a significant reduction in HbA1c in patients aged ≥ 65 years (− 0.2%) or with HbA1c ≥ 8.0% (− 0.3%) after switching from glargine 100 or 300 units/mL [15]. In this study, IDegLira showed larger reduction in HbA1c than IDegAsp (− 0.79% versus − 0.17%, respectively; p = 0.003) after switching from basal insulin therapy. Recently, a randomized crossover study investigated the efficacy of IDegLira versus IDegAsp, using intermittently scanned continuous glucose monitoring [16]. It showed a longer time in the target glucose range during the IDegLira period than that during the IDegAsp period (86.3% versus 76.3%, respectively). In this trial, the mean insulin doses were 15 units during the IDegLira period and 18 units during the IDegAsp period; the doses were similar to those in our study. This higher time in the target glucose range and lower % coefficient of variation of glucose would lead to a long-term larger reduction in HbA1c in IDegLira, even with a small dose of liraglutide. The reduction of HbA1c was considered to be due to switching to IDegAsp or IDegLira because oral antihyperglycemic agents were effectively unchanged. Moreover, despite approximately 80% of the IDegLira group used DPP4 inhibitors, one of incretine-based medicines, and stopped them when IDegLira administered, IDegLira showed large reduction in HbA1c. Therefore, IDegLira may be a viable option for patients with poor control with basal insulin and DPP4 inhibitors.
The DUAL VII trial showed that IDegLira decreased body weight by 0.9 kg after switching from basal insulin therapy [8]. Similarly, the DUAL II Japan trial reported a 1.5 kg reduction in body weight after switching from basal insulin to IDegLira [17]. However, the effect of IDegLira on body weight reduction in real-world studies has been inconsistent. A study from the US [10] reported a significant body weight reduction of 1.47 kg following IDegLira therapy 6 months after switching from basal insulin therapy, whereas a European multicenter study showed that body weight remained unchanged (− 0.2 kg). Because liraglutide had a dose-dependent effect of lowering postprandial glucose [18] and suppressing appetite, lower liraglutide doses in our study than those in other trials and real-world studies seem to have influenced our results on body weight change. As a matter of fact, in our subgroup of basal insulin dose at baseline ≥ 14 units, body weights in the IDegLira group showed significant reductions after switching due to the mean liraglutide dose being 0.8 mg, even though there were no differences compared to the IDegAsp group. Therefore, a free combination of GLP-1RA and basal insulin [19] or higher fixed-dose GLP-1RA and basal insulin combination therapy [20] is required to achieve weight loss.
In the current study, the IDegLira group showed a greater effect on reducing HbA1c than the IDegAsp group in subgroups with HbA1c ≥ 8.5%. It could be explained by glucose-dependent mechanism of action of GLP-1RAs which activate the GLP-1 receptor in the presence of elevated levels of glucose [21]. When insulin is titrated in T2D patients with obesity or uncontrolled glycemic control, insulin doses often increase. High insulin doses are associated with an increased risk of weight gain and hypoglycemia [1]. Our results indicated that switching to IDegLira could improve glycemic control without increasing hypoglycemic episodes in T2D patients, who showed high HbA1c at baseline. Mean basal insulin doses at baseline in the subgroups with higher values in the IDegLira group in our study were larger than those of the subgroups with lower values: [17.3 vs 12.6 units (HbA1c ≥ 8.5 vs < 8.5%), 16.6 vs 10.7 units (BMI ≥ 25 vs < 25 kg/m2) and 19.4 vs 8.7 units (basal insulin dose ≥ 14 vs < 14 units)]. These differences were related to differences in the amount of liraglutide and it could lead to subgroup interaction between baseline HbA1c and change in HbA1c, and baseline insulin dose and change in body weight.
This study had several limitations. First, the sample size was small. Second, there were differences in the index dates due to commercial time lags. Third, the observational period of this study may not have been sufficiently long. Fourth, endogenous insulin secretion was not assessed in this study. One of the actions of GLP-1RA is glucose-dependent insulin secretion in islet cells [21]. A report from Japan showed that insulin secretion parameters might be useful predictors of the efficacy of liraglutide [22]. Despite these limitations, this is the first study to clarify the effectiveness of IDegLira compared to the widely used premixed insulin, IDegAsp, in patients with T2D in a real-world clinical setting.
Conclusions
In conclusion, our retrospective, observational study showed that once-daily IDegLira regimens provided a greater reduction in HbA1c levels and a lesser increase in total insulin doses than once-daily IDegAsp, with comparable changes in body weight after switching from basal insulin therapy. The IDegLira group had a greater effect on HbA1c levels than the IDegAsp group in patients with high HbA1c levels. Prospective studies with a larger number of patients are necessary to confirm these results.
Author contributions
J.O. contributed to the study design, data collection, data analysis, and the development of the manuscript. T.N., Y.H., A.K., M.S., R.K., R.S. and Y.K. contributed the study design, performed the statistical analysis, and the development of the manuscript. T.B. researched data, edited and reviewed the manuscript. All authors were involved in discussion about the results and in writing the manuscript and have approved this manuscript.
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Data availability
All data generated or analyzed during this study are included in this published article. The data are not publicly available due to ethical restrictions. However, the datasets are available from the corresponding author on reasonable request.
Declarations
Conflict of interest
T Babazono has received honoraria for lectures from Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co. Ltd., Sanofi K.K., Novo Nordisk Pharma Ltd., Sumitomo Pharma Co. Ltd., Sanwa Kagaku Kenkyusyo Co. Ltd.; has received research support from Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Women’s Health Japan K.K.; and has received grants from Sanwa Kagaku Kenkyusyo Co. Ltd., Sumitomo Pharma Co. Ltd., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Abbott Japan LLC. T Nakagami reported personal fee from Sanwa Kagaku Kenkyusho Co Ltd, Novo Nordisk Pharma Ltd Japan, Eli Lily Japan KK, Sanofi K.K., Sumitomo Pharma, and Boehringer Ingelheim Japan Inc. Other authors declare that they have no conflict interest.
Ethical standard
The study was approved by the Ethics Review Committee of Tokyo Women’s Medical University (Approval no. 2481-R3, November 18, 2022). All clinical investigations were conducted in accordance with the tenets of the Declaration of Helsinki.
Informed consent
Because of the retrospective observational design, written informed consent was not obtained from the participants, although it was obtained via the opt-out method through the website of the institution.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated or analyzed during this study are included in this published article. The data are not publicly available due to ethical restrictions. However, the datasets are available from the corresponding author on reasonable request.