ABSTRACT
Aims
To compare the efficacy and safety of the fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin degludec plus insulin aspart (IDegAsp) according to the injection time of IDegAsp.
Materials and Methods
The 24‐week, multicentre, randomised, open‐label Soli‐D study enrolled Chinese adults with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drugs (OADs). This exploratory analysis evaluated glycaemic efficacy, body weight, basal insulin daily dose and hypoglycaemia outcomes with once‐daily iGlarLixi (injected before breakfast) versus IDegAsp (injected before breakfast, lunch or dinner).
Results
Of 582 participants, 291 received iGlarLixi, with injections self‐administered before breakfast, and 291 received IDegAsp, with injections self‐administered before breakfast (n = 139), lunch (n = 54) or dinner (n = 98). Glycated haemoglobin (HbA1c) reductions from baseline to Week 24 were greater with iGlarLixi than IDegAsp injected before lunch (least squares mean difference −0.24% [−2.3 mmol/mol]) or dinner (−0.29% [−3.2 mmol/mol]), and slightly greater than IDegAsp injected before breakfast (−0.12% [−1.3 mmol/mol]). Average 2‐h postprandial glucose (2‐h PPG) reductions were also greater with iGlarLixi than IDegAsp, regardless of injection time. iGlarLixi provided additional benefits, including reduced body weight, lower total insulin doses and less hypoglycaemia risk compared with IDegAsp in all injection‐time subgroups.
Conclusions
Once‐daily iGlarLixi, injected before breakfast, was associated with improved HbA1c control and greater average 2‐h PPG reductions compared with IDegAsp, regardless of injection time, in Chinese adults with T2D suboptimally controlled with OADs.
Keywords: basal insulin, GLP‐1 analogue, glycaemic control, iGlarLixi, type 2 diabetes
1. Introduction
Globally, China has the largest number of adults (aged 20–79 years) with diabetes, with 148 million people reported in 2024 and 168 million predicted by 2050 [1]. People with type 2 diabetes (T2D) often require treatment intensification to achieve and maintain glycated haemoglobin (HbA1c) targets [2]. Treatment pathways are complex, but the American Diabetes Association (ADA) guidelines and a consensus report from the ADA/European Association for the Study of Diabetes (EASD) recommend initiation of injectable glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) in most individuals prior to insulin if injectable therapy is needed to reduce HbA1c [3, 4]. The 2024 Chinese Diabetes Society (CDS) guidelines recommend initiating monotherapy in individuals with T2D based on concurrence of or at high risk for atherosclerotic cardiovascular disease (ASCVD), heart failure (HF) or chronic kidney disease (CKD) [5]. For individuals who do not achieve HbA1c targets with monotherapy, the CDS guidelines recommend dual therapy with one additional class of antidiabetic agent, including basal insulin and fixed‐dose or fixed‐ratio combinations of basal insulin and GLP‐1 RAs [5].
Once‐daily iGlarLixi is a titratable, fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide for adults with T2D who require treatment intensification due to suboptimal glycaemic control. In the global LixiLan clinical development programme, iGlarLixi demonstrated improved glycaemic control and safety compared with insulin glargine 100 U/mL (Gla‐100) or lixisenatide alone [6, 7, 8]. The efficacy and safety of iGlarLixi were also shown in Asian populations with suboptimally controlled T2D on OADs (LixiLan‐O‐AP) or basal insulin plus OADs (LixiLan‐L‐CN) [9, 10].
Soli‐D (NCT05413369) was a phase 3, randomised, open‐label, head‐to‐head study that compared once‐daily iGlarLixi with a premixed insulin (insulin degludec plus insulin aspart [IDegAsp]) in Chinese adults with T2D suboptimally controlled with previous metformin treatment (with or without another OAD) [11]. In the primary analysis of Soli‐D, iGlarLixi demonstrated significantly better glycaemic control and body weight benefits compared with IDegAsp at Week 24, with lower insulin doses and less hypoglycaemia risk, as well as significantly better control of 2‐h postprandial glucose (2‐h PPG) across all meals [11]. Interestingly, an additional analysis found that greater reductions in average 2‐h PPG (i.e., the mean 2 h PPG of all meals) and 2‐h PPG after breakfast or lunch, all assessed by 7‐point self‐monitoring plasma glucose (SMPG), were observed with iGlarLixi versus IDegAsp [12]. Although no difference between treatments was observed for 2‐h PPG after dinner, the overall PPG‐lowering effect of iGlarLixi across all meals was clinically relevant and within the CDS guideline recommended 2‐h PPG target (≤ 10.0 mmol/L) [5, 12]. In Soli‐D, iGlarLixi was injected before the first meal of the day while IDegAsp was injected before the main meal of the day (breakfast, lunch or dinner), so these findings suggest that the timing of injection of each therapy may impact 2‐h PPG outcomes [12].
In the current exploratory analyses of Soli‐D, we evaluated the impact of the injection time of iGlarLixi and IDegAsp on clinical outcomes in Chinese adults with T2D suboptimally controlled with OADs.
2. Materials and Methods
2.1. Study Design
Soli‐D was a phase 3, open‐label, randomised, multicentre trial (ClinicalTrials.gov identifier: NCT05413369), for which the design has been described previously [11]. Briefly, the study enrolled Chinese adults (aged ≥ 18 years) with T2D and suboptimally controlled HbA1c (7.5%–11.0% [58–97 mmol/mol] with metformin ± a SGLT2 inhibitor or 7.0%–10.0% [53–86 mmol/mol] with metformin + a non‐SGLT2 inhibitor OAD).
Participants received iGlarLixi (Soliqua; Sanofi, Paris, France) or IDegAsp (Ryzodeg 70/30; Novo Nordisk, Bagsværd, Denmark) for 24 weeks. At the initiation of Soli‐D, iGlarLixi did not yet have market approval in China, so it was self‐administered by subcutaneous injection once daily in the hour before the first meal (i.e., before breakfast) for consistency with previously conducted studies [6, 7, 8, 9, 10]. In contrast, consistent with the approved label in China [13], IDegAsp was self‐administered once daily before the largest meal of the day (breakfast, lunch or dinner). The timing of the IDegAsp injection was decided at the discretion of the participants and investigators at randomisation and remained the same throughout the study.
The study was conducted in accordance with the Declaration of Helsinki and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines for Good Clinical Practice. All participants provided written informed consent prior to the start of the study.
2.2. Endpoints
This exploratory analysis assessed the efficacy and safety outcomes of iGlarLixi (injected before breakfast) versus IDegAsp (injected before breakfast, before lunch or before dinner). Efficacy outcomes included the change from baseline in HbA1c at Week 24 (primary endpoint) and the proportion of participants at HbA1c target (< 7.0% [< 53 mmol/mol]), at HbA1c target without body weight gain, and at HbA1c target without body weight gain or hypoglycaemia (ADA Level 1, 2 or 3) [2]. Changes from baseline to Week 24 in fasting plasma glucose (FPG), 2‐h PPG (measured by 7‐point SMPG) and body weight, as well as the basal insulin daily dose at Week 24, were also assessed.
Safety was assessed by the incidence and event rates of ADA Level 1, 2 or 3 hypoglycaemia at Week 24. ADA Level 1 hypoglycaemia was defined as a measurable plasma glucose of ≥ 3.0 to < 3.9 mmol/L; ADA Level 2 hypoglycaemia was defined as a measurable plasma glucose < 3.0 mmol/L; and ADA Level 3 hypoglycaemia was defined as a severe hypoglycaemia event characterised by altered mental and/or physical functioning requiring assistance [2].
2.3. Statistical Analysis
The efficacy outcomes were conducted using data from the intent‐to‐treat (ITT) population, defined as all randomised participants. The primary efficacy endpoint was analysed using a multiple imputation strategy and an analysis of covariance model that included the randomisation stratum of previous OADs (yes, no) and treatment arm as the fixed categorical effects, and baseline HbA1c as the continuous covariate. Continuous secondary efficacy endpoints (i.e., FPG, 2‐h PPG and body weight) were analysed using the same approach as the primary endpoint, including the randomisation stratum of HbA1c (< 8%, ≤ 8% [< 64, ≥ 64 mmol/mol]) and the corresponding baseline value as fixed covariates. The insulin dose was analysed using a mixed model with repeated measures approach that included treatment arm, visit, randomisation strata (HbA1c, previous OADs) and treatment‐by‐visit interaction as fixed effects. Categorical secondary efficacy endpoints (i.e., HbA1c target and composite outcomes) were analysed using a logistic regression model adjusted for treatment arm, randomisation strata (HbA1c, previous OADs) and continuous baseline HbA1c. As adjustment for multiplicity was not conducted, all statistical findings were considered nominal.
Safety analyses were based on data from the safety population, defined as all randomised participants who received ≥ 1 dose of study drug. The odds ratio (OR) for the incidence of hypoglycaemia with iGlarLixi versus IDegAsp was estimated by logistic regression and the relative risk (RR) for the hypoglycaemia event rate was estimated by negative binomial regression. Both regression analyses were adjusted for treatment arm and randomisation strata (HbA1c, previous OADs). In the negative binomial regression, the logarithm of the duration (in years) of the randomised treatment period was used as the offset variable.
All statistical analyses were undertaken using SAS version 9.4 software (SAS Institute; Cary, NC, USA).
3. Results
3.1. Study Participants
Of the 582 Chinese people in the ITT population of the Soli‐D study [11], 291 participants were randomised to treatment with iGlarLixi and 291 with IDegAsp (139 injected before breakfast, 54 before lunch and 98 before dinner). Of these, 581 participants were included in the safety population (iGlarLixi: n = 290; IDegAsp: n = 291).
Demographic, baseline, and disease characteristics were balanced between the treatment arms and subgroups defined by IDegAsp time of injection (Table S1).
3.2. Efficacy
3.2.1. Glycaemic Endpoints
At Week 24, mean HbA1c reductions from baseline were greater with iGlarLixi than with IDegAsp injected before lunch and before dinner and numerically greater with iGlarLixi than with IDegAsp injected before breakfast (Figure 1). The LSM ± SE change in HbA1c from baseline was −1.88% ± 0.05% (−20.6 ± 0.5 mmol/mol) with iGlarLixi versus −1.76% ± 0.07% (−19.2 ± 0.8 mmol/mol), −1.64% ± 0.11% (−17.9 ± 1.2 mmol/mol) and −1.59% ± 0.08% (−17.4 ± 0.9 mmol/mol) with IDegAsp injected before breakfast, lunch and dinner, respectively.
FIGURE 1.
Change in HbA1c from baseline at 24 weeks in the ITT population by IDegAsp injection‐time subgroup. BB, before breakfast; BD, before dinner; BL, before lunch; CI, confidence interval; HbA1c, glycated haemoglobin; IDegAsp, insulin degludec plus insulin aspart; iGlarLixi, insulin glargine 100 U/mL plus lixisenatide; ITT, intention‐to‐treat; LSM, least squares mean; SE, standard error.
iGlarLixi was associated with higher proportions of participants achieving target HbA1c (< 7% [< 53 mmol/mol]; Figure 2a), target HbA1c without body weight gain (Figure 2b) and target HbA1c without body weight gain or hypoglycaemia (Figure 2c) at 24 weeks compared with IDegAsp injected before breakfast, lunch and dinner.
FIGURE 2.
The proportion of participants who achieved (a) target HbA1c, (b) target HbA1c without body weight gain and (c) target HbA1c without body weight gain or hypoglycaemia (ADA Level 1, 2 or 3) at 24 weeks in the ITT population by IDegAsp injection‐time subgroup. ADA, American Diabetes Association; BB, before breakfast; BD, before dinner; BL, before lunch; CI, confidence interval; HbA1c, glycated haemoglobin; IDegAsp, insulin degludec plus insulin aspart; iGlarLixi, insulin glargine 100 U/mL plus lixisenatide; ITT, intention‐to‐treat; OR, odds ratio. aEstimated by logistic regression, adjusted for randomisation strata and corresponding baseline value. bParticipants without HbA1c data at 24 weeks were considered non‐responders. cParticipants without HbA1c or body weight data at 24 weeks were considered non‐responders.
The reductions in FPG from baseline were similar with iGlarLixi and IDegAsp in all injection‐time subgroups at Week 24. The LSM ± SE change in FPG from baseline was −3.18 ± 0.11, −3.23 ± 0.16, −3.64 ± 0.24 and −3.66 ± 0.18 mmol/L with iGlarLixi, IDegAsp injected before breakfast, IDegAsp injected before lunch and IDegAsp injected before dinner, respectively. At Week 24, mean ± SD FPG levels met the CDS‐recommended FPG target of ≤ 7.0 mmol/L5 with both iGlarLixi and IDegAsp.
iGlarLixi was associated with greater reductions in the average 2‐h PPG from baseline to Week 24 compared with IDegAsp in all injection‐time subgroups (Figure S1a), whereas the average 7‐point SMPG was reduced with iGlarLixi versus IDegAsp injected before breakfast, before lunch or before dinner (Figure S1b).
At Week 24, the 2‐h PPG after each meal was at target (< 180 mg/dL [< 10 mmol/L]) with iGlarLixi at all three PPG time points (after breakfast, lunch and dinner) in the 7‐point SMPG analysis (Figure 3). Compared with iGlarLixi, all IDegAsp subgroups exhibited higher 2‐h PPG after breakfast, while participants who received IDegAsp injected before breakfast or before dinner had elevated 2‐h PPG after lunch. Notably, participants who received IDegAsp injected before dinner failed to achieve target 2‐h PPG levels after both breakfast and lunch.
FIGURE 3.
Mean 7‐point SMPG profile at baseline and 24 weeks in the ITT population by IDegAsp injection‐time subgroup. BB, before breakfast; BD, before dinner; BL, before lunch; IDegAsp, insulin degludec plus insulin aspart; iGlarLixi, insulin glargine 100 U/mL plus lixisenatide; ITT, intention‐to‐treat; SE, standard error; SMPG, self‐monitoring plasma glucose.
3.2.2. Body Weight
Participants in the iGlarLixi arm had no clinically relevant change in body weight from baseline to Week 24 (LSM ± SE change −0.30 ± 0.29 kg), whereas body weight was increased among those who received IDegAsp injected before breakfast, lunch or dinner (+1.20 ± 0.39, +1.47 ± 0.51 and +1.01 ± 0.40 kg, respectively). The LSM difference in body weight change was in favour of iGlarLixi over all IDegAsp injection‐time subgroups (−1.5 kg [95% CI −2.43, −0.57], −1.77 kg [−2.92, −0.63] and −1.3 kg [−2.27, −0.35] vs. IDegAsp before breakfast, lunch and dinner, respectively; Figure S2).
3.2.3. Basal Insulin Daily Dose
At Week 24, the total insulin daily dose was lower with iGlarLixi versus IDegAsp in all injection‐time subgroups (Figure S3).
3.3. Safety
Event rates of any hypoglycaemia (ADA Level 1, 2 or 3) were numerically lower with iGlarLixi versus IDegAsp across all injection‐time subgroups (Table 1). ADA Level 1 asymptomatic hypoglycaemia showed a lower incidence (OR 0.54; 95% CI 0.32, 0.91) and event rate (RR 0.55; 95% CI 0.31, 0.97) with iGlarLixi versus IDegAsp injected before dinner. A lower event rate of ADA Level 1 symptomatic hypoglycaemia was also observed with iGlarLixi versus IDegAsp injected before breakfast (RR 0.49; 95% CI 0.30, 0.81). No ADA Level 3 hypoglycaemia events were reported in either treatment arm.
TABLE 1.
Hypoglycaemia outcomes at 24 weeks in the safety population by IDegAsp time of injection subgroup.
| iGlarLixi (n = 290) | IDegAsp | |||
|---|---|---|---|---|
| BB (n = 139) | BL (n = 54) | BD (n = 98) | ||
| Hypoglycaemia incidence | ||||
| Any hypoglycaemia, n (%) | 102 (35.2) | 53 (38.1) | 22 (40.7) | 43 (43.9) |
| OR (95% CI) a | — | 0.90 (0.59, 1.37) | 0.76 (0.42, 1.39) | 0.70 (0.43, 1.12) |
| ADA Level 1 hypoglycaemia, b n (%) | 96 (33.1) | 51 (36.7) | 22 (40.7) | 42 (42.9) |
| OR (95% CI) a | — | 0.87 (0.57, 1.33) | 0.69 (0.38, 1.27) | 0.66 (0.41, 1.06) |
| Symptomatic | 53 (18.3) | 34 (24.5) | 10 (18.5) | 19 (19.4) |
| OR (95% CI) a | — | 0.70 (0.43, 1.14) | 0.92 (0.43, 1.96) | 0.94 (0.52, 1.69) |
| Asymptomatic | 58 (20.0) | 31 (22.3) | 16 (29.6) | 31 (31.6) |
| OR (95% CI) a | — | 0.89 (0.54, 1.46) | 0.57 (0.30, 1.11) | 0.54 (0.32, 0.91) |
| ADA Level 2 hypoglycaemia, c n (%) | 20 (6.9) | 13 (9.4) | 1 (1.9) | 11 (11.2) |
| OR (95% CI) a | — | 0.72 (0.35, 1.50) | 3.76 (0.49, 28.70) | 0.59 (0.27, 1.27) |
| ADA Level 3 hypoglycaemia, d n (%) | 0 | 0 | 0 | 0 |
| Hypoglycaemia event rate | ||||
| Total PY | 28.2 | 62.7 | 24.9 | 44.9 |
| No. of any hypoglycaemia events (rate per PY) | 243 (1.90) | 177 (2.82) | 50 (2.01) | 133 (2.96) |
| RR (95% CI) e | — | 0.70 (0.47, 1.04) | 0.89 (0.50, 1.58) | 0.66 (0.43, 1.03) |
| No. of ADA Level 1 events b (rate per PY) | 220 (1.72) | 151 (2.41) | 47 (1.89) | 119 (2.65) |
| RR (95% CI) e | — | 0.73 (0.49, 1.09) | 0.86 (0.48, 1.52) | 0.67 (0.43, 1.04) |
| Symptomatic | 84 (0.66) | 87 (1.39) | 19 (0.76) | 34 (0.76) |
| RR (95% CI) e | — | 0.49 (0.30, 0.81) | 0.76 (0.35, 1.64) | 0.92 (0.50, 1.69) |
| Asymptomatic | 136 (1.06) | 64 (1.02) | 28 (1.12) | 85 (1.89) |
| RR (95% CI) e | — | 1.04 (0.61, 1.78) | 0.89 (0.42, 1.88) | 0.55 (0.31, 0.97) |
| No. of ADA Level 2 events c (rate per PY) | 23 (0.18) | 26 (0.41) | 3 (0.12) | 14 (0.31) |
| RR (95% CI) e | — | 0.47 (0.22, 1.03) | 1.47 (0.35, 6.16) | 0.60 (0.25, 1.48) |
| No. of ADA Level 3 events d (rate per PY) | 0 | 0 | 0 | 0 |
Abbreviations: ADA, American Diabetes Association; CI, confidence interval; HbA1c, glycated haemoglobin; IDegAsp, insulin degludec plus insulin aspart; iGlarLixi, insulin glargine 100 U/mL plus lixisenatide; No., number; OADs, oral antidiabetic drugs; OR, odds ratio; PY, participant year; RR, relative risk.
Determined by logistic regression, adjusted for treatment group and randomisation strata (HbA1c, previous OADs).
Defined as a measurable plasma glucose < 3.9 to ≥ 3.0 mmol/L.
Defined as a measurable plasma glucose < 3.0 mmol/L.
Defined as a severe hypoglycaemia event characterised by altered mental and/or physical functioning requiring assistance.
Determined by negative binomial regression, adjusted for treatment group and randomisation strata (HbA1c, previous OADs), with the logarithm of the duration (in years) of the open‐label, randomised treatment period used as an offset variable.
4. Discussion
This exploratory analysis of the Soli‐D study found that once‐daily iGlarLixi, injected before breakfast, was associated with improved HbA1c control and greater average 2‐h PPG reductions compared with IDegAsp when injected before breakfast, lunch or dinner in Chinese adults with T2D suboptimally controlled with OADs. iGlarLixi also provided better body weight benefits with lower insulin doses and less hypoglycaemia risk versus IDegAsp, regardless of IDegAsp injection time. The improved HbA1c and 2‐h PPG reductions with iGlarLixi versus IDegAsp are mainly attributed to the prandial GLP‐1 RA component of iGlarLixi (lixisenatide), which primarily improves postprandial hyperglycaemia across all three meals with once‐daily administration by reducing glucagon secretion and delaying gastric motility [14]. In contrast, the fast‐acting component of IDegAsp (insulin aspart) has the greatest PPG‐lowering effect in the first 4 h after injection [15], which is why its once‐daily administration should be before the largest meal of the day [13].
The optimal injection time of once‐daily iGlarLixi was previously evaluated in a pooled analysis of data from two European REALI observational studies [16]. This previous analysis, which included 1303 adults with T2D who self‐administered iGlarLixi for 24 weeks, found that HbA1c reductions from baseline were significantly greater in individuals who received pre‐breakfast iGlarLixi injection than in those who received pre‐lunch injection (LSM difference 0.30% [3.3 mmol/mol]; p = 0.002) or those who changed injection time (LSM difference 0.24% [2.6 mmol/mol]; p = 0.02), and numerically greater with pre‐breakfast versus pre‐dinner injection (LSM difference 0.15% [1.6 mmol/mol]; p = 0.08) [16]. These findings suggest that pre‐breakfast iGlarLixi administration is associated with more effective glycaemic control than pre‐lunch or pre‐dinner IDegAsp injection. It is important to note that, according to its European and Chinese product labels, iGlarLixi should be injected within 1 h before the most convenient (preferably the same) meal each day [17, 18], whereas its United States (US) product label states it should be injected within the hour prior to the first meal of the day [19]. Of note, iGlarLixi is available as a 100/33 pre‐filled injection pen in the US, 100/33 and 100/50 injection pens in Europe and 100/50 and 100/100 injection pens in China, with the different pens providing alternative ratios of Gla‐100 to lixisenatide. A benefit to these different pen alternatives is that they allow for the maximisation of the GLP‐1 RA dose in individuals who typically require lower insulin doses, like those in China.
In the current exploratory analysis of Soli‐D, participants in the iGlarLixi arm had similar reductions in FPG from baseline to Week 24 to those in the IDegAsp arm, regardless of injection time. The similarity in FPG reductions may be explained, at least in part, by the treat‐to‐target design of the Soli‐D study, in which the median of the last three FPG measurements was used to determine the basal insulin daily dose adjustments [11]. Furthermore, approximately 30% of participants in the IDegAsp arm received treatment before dinner, maximising FPG control, which was measured in the morning. In contrast, participants in the iGlarLixi group had FPG measured prior to injection in the morning, meaning that FPG was measured up to 24 h after the preceding dose.
With regards to hypoglycaemia, iGlarLixi was associated with a lower risk of ADA Level 1 asymptomatic hypoglycaemia than IDegAsp injected before dinner, and a lower risk of ADA Level 1 symptomatic hypoglycaemia than IDegAsp injected before breakfast. The lower total insulin daily dose with iGlarLixi versus IDegAsp across all injection‐time subgroups most likely led to this lower risk of ADA Level 1 asymptomatic and symptomatic hypoglycaemia with iGlarLixi, as lower insulin doses may carry a lower hypoglycaemia risk [20]. Furthermore, the increased risk of asymptomatic and symptomatic hypoglycaemia with pre‐dinner and pre‐breakfast IDegAsp injection, respectively, may provide insights into how the IDegAsp injection time can influence safety outcomes, thereby informing best practice for treatment with this premixed insulin in the routine T2D management.
This analysis has some limitations that should be considered when interpreting these results. The exploratory nature of this analysis means that the sample size and power calculations conducted for the Soli‐D study primary endpoint may not be applicable; therefore, all statistical inferences were nominal and the findings of this analysis should be considered as hypothesis generating. Furthermore, because the IDegAsp injection time was determined by the participant or investigator, rather than randomised, the resulting unequal size of injection‐time subgroups and potential confounding factors may limit the interpretation of the causal effects of injection time. Therefore, additional prospective studies on the impact of the time of insulin injection and outcomes are needed to confirm these findings. In addition, because Soli‐D was a phase 3 randomised clinical trial in Chinese people with T2D, further real‐world studies are needed to confirm the glycaemic effectiveness of iGlarLixi over IDegAsp in other populations of people with suboptimally controlled T2D.
In conclusion, once‐daily iGlarLixi administered before breakfast was associated with greater reductions in HbA1c and average 2‐h PPG than IDegAsp in Chinese adults suboptimally controlled T2D on prior OADs, regardless of the IDegAsp injection time. Notably, when iGlarLixi and IDegAsp were both administered before breakfast, participants in the iGlarLixi arm achieved better overall glycaemic control with lower insulin doses, reduced hypoglycaemia risk, and favourable body weight effects versus those in the IDegAsp arm. These findings further support the efficacy and safety of iGlarLixi as a valuable once‐daily treatment intensification option in people with suboptimally controlled T2D in China.
Author Contributions
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article and had full access to all the data in this study, and take full responsibility for the integrity of the data and accuracy of the data analysis. Agustina Alvarez, Felipe Lauand, Lei Kang, Qin Du and Ming Liu were involved in the conception, design and conduct of the study. Xin Li, Juan Wang, Tong Liu, Agustina Alvarez, Felipe Lauand, Lydie Melas‐Melt, Lei Kang, Qin Du and Ming Liu were involved in the analysis and interpretation of the results. All the authors edited, reviewed and approved the final version of the manuscript.
Funding
This work was supported by Sanofi China Investment Company.
Conflicts of Interest
Xin Li, Juan Wang, Tong Liu, and Ming Liu have nothing to disclose. Agustina Alvarez, Felipe Lauand, Lei Kang, and Qin Du are Sanofi employees. Lydie Melas‐Melt is an employee of Ividata Life Sciences, contracted by Sanofi.
Supporting information
TABLE S1: Baseline demographics and disease characteristics in the ITT population by IDegAsp injection‐time subgroup.
FIGURE S1: Change in (a) average 2‐h PPG and (b) average 7‐point SMPG from baseline at 24 weeks in the ITT population by IDegAsp injection‐time subgroup.
FIGURE S2: Change in body weight from baseline at 24 weeks in the ITT population by IDegAsp injection‐time subgroup.
FIGURE S3: Total daily insulin dose at 24 weeks in the ITT population by IDegAsp injection‐time subgroup.
Acknowledgements
We would like to thank the study participants, trial staff and investigators of the Soli‐D study for their participation. We would also like to thank Sarah Greig, PhD, CMPP, and Simone Tait, CMPP, of Springer Health+ who assisted in the preparation of the outline and subsequent drafts of the manuscript and post‐submission revisions. This medical writing assistance was funded by Sanofi, Beijing, China.
Li X., Wang J., Liu T., et al., “Impact of Time of Injection on the Efficacy and Safety of iGlarLixi Versus IDegAsp in Chinese People With Type 2 Diabetes: Exploratory Analysis of the Soli‐D Study,” Diabetes, Obesity and Metabolism 28, no. 8 (2026): 6965–6972, 10.1111/dom.70902.
Handling Editor: Ricahrd Donnelly
Data Availability Statement
Qualified researchers may request access to patient‐level data and related documents. 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: Baseline demographics and disease characteristics in the ITT population by IDegAsp injection‐time subgroup.
FIGURE S1: Change in (a) average 2‐h PPG and (b) average 7‐point SMPG from baseline at 24 weeks in the ITT population by IDegAsp injection‐time subgroup.
FIGURE S2: Change in body weight from baseline at 24 weeks in the ITT population by IDegAsp injection‐time subgroup.
FIGURE S3: Total daily insulin dose at 24 weeks in the ITT population by IDegAsp injection‐time subgroup.
Data Availability Statement
Qualified researchers may request access to patient‐level data and related documents. 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.