Summary: In a post hoc analysis of the LixiLan-L-CN randomised trial, among Chinese adults with type 2 diabetes and baseline residual hyperglycaemia (HbA1c at least 7.0% with fasting plasma glucose below 7.0 mmol/L) on prior basal insulin, the fixed-ratio combination iGlarLixi reduced the residual hyperglycaemia rate to 7.0% at week 30 versus 43.3% with insulin glargine alone. The HbA1c least-squares-mean difference favoured iGlarLixi by 0.9% and the 2-hour postprandial glucose difference by 4.7 mmol/L (both P less than 0.001), with similar hypoglycaemia. These are secondary, hypothesis-generating findings.
PICO Summary
| Element | Detail |
|---|---|
| Population | Post hoc subgroup of the LixiLan-L-CN multicentre randomised controlled trial (NCT03798080), China. Of 421 randomised adults with type 2 diabetes suboptimally controlled on prior basal insulin with or without oral agents, 124 (29.5%) had baseline residual hyperglycaemia (HbA1c at least 7.0% [at least 53 mmol/mol] with fasting plasma glucose below 7.0 mmol/L) and formed the analysis set. |
| Intervention | iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, over 30 weeks (n = 64 [31.7%] of the residual-hyperglycaemia subgroup). |
| Comparison | Insulin glargine 100 U/mL (iGlar) alone over 30 weeks (n = 60 [29.1%] of the residual-hyperglycaemia subgroup). |
| Outcome | At week 30 the residual hyperglycaemia rate fell to 7.0% with iGlarLixi but rose to 43.3% with iGlar. More participants achieved both HbA1c and fasting plasma glucose targets with iGlarLixi (43.8% vs 16.7%). iGlarLixi gave greater reductions in HbA1c (least-squares-mean difference -0.9% [-9.4 mmol/mol]) and in 2-hour postprandial glucose (least-squares-mean difference -4.7 mmol/L), both P less than 0.001. Daily basal insulin dose and hypoglycaemia incidence were similar between groups. No 95% confidence intervals, absolute risk reductions or numbers-needed-to-treat were reported in the abstract. |
iGlarLixi vs iGlar for residual hyperglycaemia
Post hoc RCT · type 2 diabetes · 30 weeks
iGlarLixi cut residual hyperglycaemia from 43.3% to 7.0% at 30 weeks, with similar hypoglycaemia. Post hoc, open-label, sponsor-funded subgroup, so hypothesis-generating.
Expert Commentary
This is a post hoc subgroup analysis of an open-label randomised trial, so the results are best read as supportive and hypothesis-generating rather than as confirmatory evidence. Residual hyperglycaemia here is a composite definition (HbA1c at or above target despite a controlled fasting glucose), which the prandial action of lixisenatide is mechanistically suited to address, so the direction of benefit is plausible. The reported separation is large: a fall to 7.0% versus a rise to 43.3%, with a 2-hour postprandial glucose difference of 4.7 mmol/L. Several cautions temper enthusiasm. The trial was funded by the manufacturer and several authors are employees of the sponsor, the open-label design cannot blind the differing injection regimens, and the subgroup was small (124 of 421) and defined after the fact, which inflates the risk of chance findings. No confidence intervals or absolute risk measures were given, limiting precision. Can I use this with my patients? Reasonably yes, for an adult with type 2 diabetes whose fasting glucose is at goal on basal insulin but whose HbA1c and postprandial readings remain high, iGlarLixi is a defensible intensification option, provided hypoglycaemia and gastrointestinal tolerability are monitored. A prospective trial powered for this phenotype would settle the question.
References
Yuan X, Li D, Wang K, Lauand F, Zhang M, Fang H, et al. iGlarLixi effectively reduces residual hyperglycaemia in Chinese people with type 2 diabetes on basal insulin: A post hoc analysis of the LixiLan-L-CN study. Diabetes Obes Metab. 2024;26(12):5942-5949. doi:10.1111/dom.15968
