iGlarLixi trumps biphasic insulin for glycaemic control, weight loss in poorly controlled T2D

Once-daily iGlarLixi is superior to twice-daily premixed biphasic insulin aspart 30 (BIAsp 30) in glycaemic control and reducing body weight, along with less risk of hypoglycaemia, in patients with suboptimally controlled type 2 diabetes (T2D) despite treatment with basal insulin plus oral antihyperglycaemic drugs (OADs), according to the SoliMix trial presented at ADA 2021.

iGlarLixi is a fixed-ratio combination of basal insulin glargine and the short-acting GLP-1 RA* lixisenatide — which provides complementary mechanisms of action of both the components in one formulation.

After 26 weeks of treatment, not only was iGlarLixi noninferior to BIAsp 30 in reducing HbA1c from baseline (by 1.3 percent vs 1.1 percent, respectively; p<0.001 for noninferiority), it also met the superiority criteria for this endpoint (p<0.001). [Diabetes Care 2021;doi:10.2337/dc21-0393]

In addition, iGlarLixi was superior to BIAsp 30 for the coprimary endpoint of bodyweight reduction at week 26 (mean bodyweight change, -0.7 vs 1.2 kg; least-squares [LS] mean difference, -1.9; p<0.001).

Moreover, the better glycaemic control was achieved with less hypoglycaemia events in the iGlarLixi vs the BIAsp 30 groups. Fewer patients treated with iGlarLixi experienced at least one hypoglycaemic event compared with the BIAsp 30 group (odds ratio [OR], 0.62, 95 percent confidence interval [CI], 0.47–0.81).

Considering the multiple endpoints together, the iGlarLixi group was more likely to achieve the target HbA1c of <7 percent without weight gain (27.5 percent vs 12.4 percent; OR, 2.83; p<0.001) as well as achieving both outcomes without hypoglycaemia (19.4 percent vs 7.0 percent; OR, 3.40; p<0.001).

“It is, therefore, very encouraging that lower incidence and rates of hypoglycaemia, including ADA Level 2 nocturnal hypoglycaemia between bedtime and waking, were still observed with iGlarLixi versus premix BIAsp 30 in the present study, despite iGlarLixi demonstrating better glycaemic control,” the researchers pointed out.

The open-label multicentre study involved 887 adults (mean age 59.8 years, 49.8 percent male) with suboptimally controlled T2D (HbA1c≥7.5 percent and ≤10 percent) despite treatment with basal insulin and OADs**. They were randomized 1:1 to receive once-daily subcutaneous iGlarLixi or twice-daily BIAsp 30 for 26 weeks.

The overall safety profile was consistent with previous studies for the individual drugs, with no new safety signals identified, according to the authors.

The most common adverse event (AE) in the iGlarLixi arm was nausea (7.7 percent vs 0 percent), while that for the BIAsp 30 arm was nasopharyngitis (2.7 percent vs 3.2 percent). Most of the AEs were mild or moderate in severity for both groups of patients. The rates of serious AEs (2.7 percent vs 2.9 percent) and discontinuation due to AEs (0.9 percent for both) was similarly low in both treatment groups.

“Our results demonstrate that a co-formulation of basal insulin and GLP-1 RA (iGlarLixi) is more efficacious than a co-formulation of a basal insulin and a prandial insulin (premix BIAsp 30) when advancing therapy for people with T2D suboptimally controlled on basal insulin alone,” said the researchers.

“In addition to improving clinical outcomes, the lower incidence of hypoglycaemia and the weight benefits observed with iGlarLixi may improve patient satisfaction, which could improve treatment adherence,” they added.

*GLP-1 RA: glucagon-like peptide-1 receptor agonist

**metformin  with or without SGLT2 inhibitor