Advancing therapy with iGlarLixi versus premix BIAsp 30 in basal insulin‐treated type 2 diabetes: Design and baseline characteristics of the SoliMix randomized controlled trial

Abstract

Aim Premix insulin is commonly used in some regions of the world, despite the higher risk of hypoglycaemia and weight gain compared with basal insulin, based on the premise that it offers a simplified insulin regimen. iGlarLixi is a once‐daily titratable fixed‐ratio formulation that combines basal insulin glargine 100 units/mL (iGlar) and the GLP‐1 RA, lixisenatide, which offers a single‐injection option for treatment intensification, with improved HbA1c reductions, similar hypoglycaemia risk and more favourable bodyweight profiles over iGlar alone. This randomized controlled study directly compares, for the first time, treatment intensification with iGlarLixi versus premix insulin analogue biphasic insulin aspart 30 (BIAsp 30) in adults with T2D inadequately controlled on basal insulin in combination with one or two oral antihyperglycaemic drugs. Materials and Methods This was an open‐label, active‐controlled, comparative, parallel‐group, multicentre, phase 3b study. In total, 887 adults with T2D uncontrolled on basal insulin were randomized to switch to either iGlarLixi once daily, or BIAsp 30 twice daily, for 26 weeks. Results Overall, 887 participants were enrolled (mean age 59.8 years, 50.2% female) from 89 centres in 17 countries. At baseline, 65.6% had a duration of T2D of 10 years or longer, and the mean HbA1c at baseline was 8.6%. Conclusions The study directly compared the efficacy and safety of iGlarLixi versus BIAsp 30 in people with T2D uncontrolled on basal insulin and one or more oral antihyperglycaemic agents. These results provide robust clinical data that may inform clinicians in their therapeutic management of people with T2D uncontrolled on basal insulin requiring additional therapy.

Titratable fixed‐ratio combination of basal insulin plus a glucagon‐like peptide‐1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes

“…Nonetheless, this evidence gap should be addressed soon by the first head-to-head trial comparing iGlarLixi and premix BIAsp 30, testing important comparative questions. 57 However, it should be noted that while data from such prospective RCTs are invaluable in providing comparative data on the efficacy and safety of therapies, results from RCTs are not always generalizable to real-life clinical practice because of high degrees of participant follow-up, stringent protocols and titration algorithms, and highlyselected populations. 59 As such, further real-world comparative effectiveness studies would be of interest to complement the results of the aforementioned RCT and explore whether the results seen in this trial are maintained in a real-life clinical practice setting.…”

“…While evidence suggests that FRCs offer clinical benefits compared with premix insulin, head‐to‐head RCTs comparing both approaches have been lacking. Nonetheless, this evidence gap should be addressed soon by the first head‐to‐head trial comparing iGlarLixi and premix BIAsp 30, testing important comparative questions 57 …”

“…SoliMix, a head‐to‐head RCT comparing the efficacy and safety of an FRC of basal insulin and a GLP‐1 RA, iGlarLixi, and premix insulin in a 30/70 ratio, biphasic insulin aspart 30/70 (BIAsp 30) in adults with T2D who have failed to reach their glycaemic targets with basal insulin plus one or two OADs, is currently in progress 57 . This 26‐week, open‐label, randomized, active‐controlled, parallel‐group, multicentre study will address a question that has previously not been properly tested in a prospective RCT, namely, assessing the comparative efficacy and safety of advancing basal insulin therapy by switching to a premix insulin regimen or by switching to a simpler once‐daily FRC, such as iGlarLixi.…”

Advancing Therapy in Suboptimally Controlled Basal Insulin–Treated Type 2 Diabetes: Clinical Outcomes With iGlarLixi Versus Premix BIAsp 30 in the SoliMix Randomized Controlled Trial

“…Detailed methods have previously been published ( 23 ). In brief, SoliMix was an open-label, multicenter, randomized, 26-week study undertaken to compare the efficacy and safety of iGlarLixi with BIAsp 30 in adults with suboptimally controlled type 2 diabetes (HbA 1c ≥7.5% [≥58.5 mmol/mol] and ≤10% [≤85.8 mmol/mol]) despite receiving stable doses of basal insulin plus OADs (metformin ± sodium–glucose cotransporter 2 [SGLT2] inhibitor) for 3 months.…”

Randomised Controlled Trials in Diabetes Research: A Pathway to Interpreting Published Results

“…An important point for readers to note is that endpoints are often analysed in a hierarchical manner, and the interpretation of results should be consistent with this analysis planfor example, to avoid problems associated with multiplicity and so-called type 1 error, secondary endpoints can only be statistically analysed or interpreted if the primary endpoint is met [30,31]. An example of this is demonstrated in the recent SoliMix trial comparing the fixed-ratio combination of iGlarLixi (basal insulin glargine 100 U/mL plus the glucagonlike peptide-1 receptor agonist lixisenatide) with the premix insulin analogue BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine) [32]. A primary endpoint of this study was the noninferiority of iGlarLixi to BIAsp 30 in HbA 1c reduction from baseline to week 26.…”