1. BACKGROUND
Type 2 diabetes (T2D) remains a major public health burden globally, with China accounting for the highest number of affected individuals. 1 Despite the widespread use of oral antidiabetic drugs (OADs), many patients fail to achieve glycaemic targets, increasing the risk of complications. 2 In such cases, advanced therapies including fixed‐ratio combinations (FRCs) or premixed insulin are recommended by the Chinese Diabetes Society. 3 iGlarLixi, a once‐daily FRC of insulin glargine 100 U/mL and GLP‐1 RA lixisenatide, combines complementary actions of lowering basal and prandial glucose levels. It has demonstrated superior efficacy and safety compared to various comparators. 4 , 5 IDegAsp is a premixed insulin formulation of 70% insulin degludec and 30% insulin aspart, recommended as a once‐daily regimen for Chinese with T2D who have suboptimal glycaemic control on OADs. 6 The Soli‐D study on Chinese adults with T2D suboptimally controlled with OADs showed that iGlarLixi had demonstrated non‐inferiority and superiority to IDegAsp in reducing glycated haemoglobin (HbA1c) levels while also providing body weight benefits and a lower risk of hypoglycaemia. 7
Beyond HbA1c, glucose time‐in‐range (TIR) derived from continuous glucose monitoring (CGM) or structured self‐measured blood glucose (SMBG) offers actionable insights into glycaemic control. 8 Derived TIR (dTIR) from 7‐point SMBG profiles correlates with HbA1c and diabetic complications and has emerged as a meaningful endpoint in clinical research. 9 This post hoc analysis of the Soli‐D study aimed to compare the efficacy of iGlarLixi versus IDegAsp using dTIR in Chinese adults with T2DM suboptimally controlled on OADs. The efficacy in subpopulations aged less than 65 years and 65 years or older was also evaluated.
2. METHODS
This post hoc analysis used data from the Soli‐D study (NCT05413369), a 24‐week, randomised, open‐label, multicentre Phase III trial comparing the efficacy and safety of once‐daily iGlarLixi versus IDegAsp in Chinese adults with T2D inadequately controlled with metformin, with or without an additional OAD. Full details have been reported previously. 7 , 10 To assess glycaemic control, seven‐point SMBG profiles were collected at baseline, Week 12, and Week 24. dTIR (70–180 mg/dL) was calculated as the percentage of readings within the target range on two separate days before each visit. Other derived metrics included time‐in‐tight‐range (dTITR; 70–140 mg/dL), derived time below range (dTBR; <70 mg/dL [<3.9 mmol/L]), with subdivisions of dTBR Level 1 (54–69 mg/dL [3.0–3.8 mmol/L]) and dTBR Level 2 (<54 mg/dL [<3.0 mmol/L]), as well as derived time above range (dTAR; >180 mg/dL [>10.0 mmol/L]), with dTAR Level 1 (181–250 mg/dL [10.1–13.9 mmol/L]) and dTAR Level 2 (>250 mg/dL [>13.9 mmol/L]). Changes from baseline to Weeks 12 and 24 were analysed, along with the proportions of participants achieving dTIR ≥70%, a ≥5% increase in dTIR from baseline, and a triple composite target of dTIR ≥70%, dTBR <4% and dTAR <25%.
Analyses included participants from the intention‐to‐treat population who have complete SMBG data at baseline and at least one follow‐up visit. Continuous variables were summarised as means (standard deviation), and categorical variables as frequencies and percentages. Changes in dTIR, dTITR, dTBR, and dTAR were assessed using a mixed model for repeated measures, adjusting for baseline values and stratification factors. Estimated treatment differences (ETDs) with 95% confidence intervals (CIs) were calculated. Target achievement rates were compared using Cochran–Mantel–Haenszel weights. Subgroup analyses by age (<65 vs. ≥65 years) were performed, with nominal interaction p‐values reported. Analyses were conducted using SAS version 9.4.
3. RESULTS
A total of 532 participants were analysed (iGlarLixi: n = 258; IDegAsp: n = 274). Overall, baseline characteristics were well‐balanced between groups (Table 1). At Week 12, iGlarLixi showed superior glycaemic control with higher mean dTIR (81.92% vs. 73.08%), dTITR (53.89% vs. 45.12%), and lower dTAR (17.96% vs. 26.75%) compared to IDegAsp. These trends persisted at Week 24 (Table S1 and Figure 1A). Between‐group differences in dTIR favoured iGlarLixi at both Week 12 (ETD: 9.62%, 95% CI: 5.93 to 13.31) and Week 24 (ETD: 8.25%, 95% CI: 4.30 to 12.20) (Tables S2 and S3). dTITR also improved more with iGlarLixi (ETD: 7.17%, 95% CI: 2.90 to 11.44), and dTAR decreased more with iGlarLixi (ETD: −8.61%, 95% CI: −12.54 to −4.68) at Week 24 with dTAR Level 1 and Level 2 following the same trend. dTBR with dTBR Level 1 and Level 2 remained low in both groups. At Week 24, more participants with iGlarLixi achieved dTIR ≥70% (76.4% vs. 65.0%), ≥5% increase in dTIR from baseline (83.3% vs. 77.7%) (Figure 1B) and composite triple target of dTIR ≥70%, dTBR <4% and dTAR <25% (63.2% vs. 46.4%).
TABLE 1.
Baseline characteristics.
| Variables | iGlarLixi (N = 258) | IDegAsp (N = 274) |
|---|---|---|
| Age, years, mean (SD) | 56.3 (10.2) | 57.2 (10.0) |
| Age group, n (%) | ||
| <50 | 56 (21.7) | 62 (22.6) |
| ≥50, < 65 | 144 (55.8) | 142 (51.8) |
| ≥65, < 75 | 57 (22.1) | 64 (23.4) |
| ≥75 | 1 (0.4) | 6 (2.2) |
| Sex, n (%) | ||
| Male | 130 (50.4) | 147 (53.6) |
| Female | 128 (49.6) | 127 (46.4) |
| Baseline BMI, kg/m2, mean (SD) | 26.01 (3.47) | 25.56 (3.22) |
| Weight, kg, mean (SD) | 70.70 (13.28) | 69.48 (12.42) |
| HbA1c, %, mean (SD) | 8.59 (0.93) | 8.52 (0.90) |
| FPG, mmol/L, mean (SD) | 10.06 (2.34) | 10.07 (2.54) |
| 2‐hour PPG, mmol/L, mean (SD) | 13.01 (2.71) | 12.78 (2.73) |
| Duration of Type 2 diabetes, years, mean (SD) | 8.75 (5.80) | 9.01 (5.91) |
| Oral antidiabetic treatment use, n (%) | ||
| Metformin ± SGLT‐2i | 132 (51.16) | 142 (51.82) |
| Metformin + other OAD | 126 (48.84) | 132 (48.18) |
| dTIR (70–180 mg/dL), %, mean (SD) | 35.94 (29.67) | 38.32 (29.84) |
| dTITR (70–140 mg/dL), %, mean (SD) | 11.85 (16.87) | 12.57 (18.56) |
| dTBR (<70 mg/dL), %, mean (SD) | 0.06 (0.89) | 0.00 (0.00) |
| dTBR Level 1 (54–69 mg/dL), %, mean (SD) | 0.06 (0.89) | 0.00 (0.00) |
| dTBR Level 2 (<54 mg/dL), %, mean (SD) | 0.00 (0.00) | 0.00 (0.00) |
| dTAR (>180 mg/dL), %, mean (SD) | 64.01 (29.72) | 61.68 (29.84) |
| dTAR Level 1 (181–250 mg/dL), %, mean (SD) | 41.75 (23.31) | 40.56 (22.76) |
| dTAR Level 2 (>250 mg/dL), %, mean (SD) | 22.26 (26.31) | 21.12 (25.71) |
Abbreviations: BMI, body mass index; DPP‐4, dipeptidyl peptidase‐4; dTAR, derived time‐above‐the‐range; dTBR, derived time‐below‐the‐range; dTIR, derived time‐in‐range; dTITR, derived time‐in‐tight‐range; FPG, fasting plasma glucose; GI, glucosidase inhibitor; OAD, oral antidiabetic drug; PPG, postprandial plasma glucose; SGLT2, sodium‐glucose co‐transporter‐2.
FIGURE 1.
(A) Mean derived time‐in‐range (dTIR), time‐above‐range (dTAR) and time‐below‐range (dTBR) at baseline, Week 12, and Week 24 in the iGlarLixi and IDegAsp groups. (B) Proportions of participants achieving dTIR ≥70% and a ≥5% increase in dTIR from baseline to week 24. (C) Changes in dTIR, dTAR, and dTBR over time in patients <65 years. (D) Changes in dTIR, dTAR, and dTBR over time in patients ≥65 years. CI, confidence interval.
In age subgroup analyses (Figure 1C), greater improvements in dTIR observed with iGlarLixi were consistent across groups. Among participants <65 years, at Week 24, iGlarLixi led to a higher dTIR increase (45.51% vs. 36.68%) and a higher achievement of dTIR ≥70% (76.00% vs. 66.18%), ≥5% increase from baseline (83.50% vs. 77.94%), and the triple target (64.00% vs. 48.04%). Similar trends were observed in participants ≥65 years (dTIR increase: 43.24% vs. 36.90%; dTIR ≥70%: 77.59% vs. 61.43%; ≥5% increase in dTIR: 82.76% vs. 77.14%; triple target: 60.34% vs. 41.43%) at Week 24.
4. DISCUSSION
Compared to HbA1c, TIR, derived from CGM or structured SMBG, provides more granular insight into glycaemic fluctuations and correlates with diabetes‐related outcomes. dTIR has gained recognition as a surrogate endpoint and aligns closely with HbA1c. Prior trials have shown that iGlarLixi improves HbA1c compared to insulin glargine or lixisenatide alone. 11 Our findings build upon the Soli‐D trial, which established the non‐inferiority and superiority of iGlarLixi over IDegAsp in HbA1c reduction and weight benefit, 7 by demonstrating that these advantages extend to SMBG‐derived metrics such as dTIR and dTITR. Notably, improvements were evident as early as Week 12 and sustained at Week 24, with higher proportions of participants achieving consensus targets for dTIR.
The glycaemic benefits of iGlarLixi may be attributed to its dual mechanism: insulin glargine provides stable basal glucose control, while lixisenatide attenuates postprandial excursions via glucose‐dependent insulin secretion, glucagon suppression, and delayed gastric emptying. 7 , 10 This design allows for enhanced glycaemic control without increasing the risk of hypoglycaemia, as reflected by consistently low dTBR values in both treatment arms. Importantly, iGlarLixi significantly reduced dTAR, including both Level 1 and Level 2 hyperglycaemia. These findings support its potential role in mitigating chronic hyperglycaemia‐related complications. 11 In subgroup analysis, iGlarLixi conferred consistent benefits in both age groups (<65 and ≥65 years), including higher proportions of achieving dTIR ≥70%, ≥5% improvement, and the composite glycaemic target. This suggests that iGlarLixi is effective across age groups and aligns with prior analyses indicating preserved efficacy and low hypoglycaemia risk in older adults. 12
This study has several limitations. The use of 7‐point SMBG instead of CGM may not fully capture glycaemic variability. Furthermore, as a post hoc analysis, it is inherently exploratory and cannot establish causality. The relatively small sample size in the ≥65 years subgroup also limits the precision of results.
In conclusion, iGlarLixi achieved greater improvement in dTIR among Chinese adults with T2D suboptimally controlled on OADs compared to IDegAsp without increasing the risk of hypoglycaemia. These results suggest that iGlarLixi offers a more effective management strategy for people living with T2D with suboptimal glycaemic control, addressing a significant clinical unmet need in the current therapeutic landscape.
FUNDING INFORMATION
Sponsorship for this study was provided by Sanofi. Editorial support was provided by Dr. Fabao Zhang of Shanghai MedSci Technology Co., Ltd and was funded by Sanofi.
CONFLICT OF INTEREST STATEMENT
YL has acted as a consultant for Sanofi, Novo Nordisk and AstraZeneca. WX is a Sanofi employee and may hold shares/stocks. MZ is a Sanofi employee and may hold shares/stocks. QH is a Sanofi employee and may hold shares/stocks. QD is a Sanofi employee and may hold shares/stocks. LK is a Sanofi employee and may hold shares/stocks. FL is a Sanofi employee and may hold shares/stocks. AA is a Sanofi employee and may hold shares/stocks.
PEER REVIEW
The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer‐review/10.1111/dom.16646.
Supporting information
Table S1. Comparison of glycaemic metrics at baseline, Week 12 and Week 24 for iGlarLixi versus IDegAsp.
Table S2. Least square (LS) mean changes in derived time‐in‐ranges from baseline to week 12 using mixed model for repeated measures (MMRM).
Table S3. Least square (LS) mean changes in derived time‐in‐ranges from baseline to week 24 using mixed model for repeated measures (MMRM).
ACKNOWLEDGEMENTS
The authors thank the study investigators, research coordinators and participants of the Soli‐D study for their participation. The Soli‐D study (NCT 05413369) was sponsored by Sanofi.
Liu J, Liu Y, Xu W, et al. Evaluation of efficacy of iGlarLixi versus IDegAsp using derived time‐in‐ranges in Chinese adults with Type 2 diabetes: A post hoc analysis of the Soli‐D study. Diabetes Obes Metab. 2025;27(10):6068‐6071. doi: 10.1111/dom.16646
DATA AVAILABILITY STATEMENT
Qualified researchers may request access to patient‐level data and related documents (including, e.g., the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications). Patient‐level data will be anonymised, and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at https://www.vivli.org.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1. Comparison of glycaemic metrics at baseline, Week 12 and Week 24 for iGlarLixi versus IDegAsp.
Table S2. Least square (LS) mean changes in derived time‐in‐ranges from baseline to week 12 using mixed model for repeated measures (MMRM).
Table S3. Least square (LS) mean changes in derived time‐in‐ranges from baseline to week 24 using mixed model for repeated measures (MMRM).
Data Availability Statement
Qualified researchers may request access to patient‐level data and related documents (including, e.g., the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications). Patient‐level data will be anonymised, and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at https://www.vivli.org.