A head-to-head study published in Diabetes Care – which compared the efficacy and safety of a once-daily fixed ratio combination of insulin glargine 100 units/mL and the glucagon-like peptide receptor agonist lixisenatide and a twice-daily premix insulin analog bisphasic aspart insulin 30 (BIAsp 30) and basal insulin plus oral antihyperglycemic drugs – indicates that the once-daily regimen may be more beneficial for patients with suboptimally controlled type 2 diabetes.
The SoliMix study was an open-label, multicenter, randomized, 26-week study. Participants were randomly assigned 1:1 to receive either once-daily subcutaneous lixisenatide twice-daily subcutaneous BIAsp 30. At baseline, participants were switched from prior basal insulin to the study medications; oral antihyperglycemic drugs were continued.
The primary study endpoints were noninferiority of lixisenatide to BIAsp 30 in terms of HbA1c, or superiority in terms of body weight change over the study period. Secondary efficacy endpoints included HbA21c less than 7% without weight gain and hypoglycemia, as well as the superiority of lixisenatide vs BIAsp 30 in HbA1c reduction from baseline through week 26.
The total cohort included 887 participants from 89 centers in 17 countries; 443 were assigned to receive lixisenatide and 444 to receive BIAsp 30. The intention-to-treat population included 403 and 404 participants in each group, respectively.
Mean duration of treatment in the lixisenatide and BIAsp 30 group were 184 and 181 days, respectively, with 95.2% of the participants (n=844) completing the full 26-week treatment period. There were 428 and 416 participants in each group, respectively.
Demographics and baseline characteristics between groups were similar. Study participants were 62.4% White; mean age was 59.8±10.2 years; and type 2 diabetes duration was 13±7.2 years. The majority of participants used metformin at baseline (99.8%), while one-fourths were also receiving a sodium-glucose cotransporter-2 inhibitor (SGLT2). At baseline, participants were receiving insulin glargine 100 units/mL (46%), insulin glargine 300 units/mL (22%), NPH (neutral protamine hagedorn) insulin (21%), insulin detemir (7%), and insulin degludec (5%).
At the end of the study, the 2 primary and 3 key secondary efficacy endpoints were met. Mean baseline HbA1c was 8.6±0.7% and 8.6±0.7% in the lixisenatide and BIAsp 30 groups, respectively. At 26 weeks, mean HbA1c improved to 7.3±1.1% and 7.5±1.-% in each group, respectively, though the statistical noninferiority of lixisenatide was demonstrated in HbA1c change (least squares [LS] mean difference, -0.2%; 97.5% CI, -0.4 to -0.1; P <0.001).
Statistical superiority in HbA1c reduction during the study period of lixisenatide was also demonstrated as part of the key secondary endpoint analysis.
At baseline, mean body weight was 80.7±16.5 kg and 82.2±18.5 kg in the lixisenatide and BIAsp 30 group, respectively; however, during the course of the study, weight decreased to 80.2±16.6 kg and increased to 83.4±19.0 kg in each group, respectively. lixisenatide was statistically superior in terms of body weight change during the study period (LS mean difference, -1.9 kg; 95% CI, -2.3 to -1.4 kg; P <.001).
An analysis of key secondary endpoints showed that a significantly higher percentage of participants in the lixisenatide group reached a target HbA1c less than 7% without weight gain by week 26, and without weight gain and hypoglycemia during the same period. The percentage of patients achieving the target HbA1c was higher in the lixisenatide vs BIAsp 30 group.
Compared with BIAsp 30, lixisenatide was also associated with higher proportions of achievement of the target HbA1c less than 7% without American Diabetes Association (ADA) level 2 hypoglycemia, HbA1c less than 7% without weight gain of greater than 1 kg, and HbA1c less than 6.5%.
At baseline, mean fasting plasma glucose (FPG) was 151±44 mg/dL and 149±41 mg/dL in the lixisenatide and BIAsp 30 group, respectively. By week 26, mean FPG was 130±44 mg/dL and 146±51 mg/dL in each group, with a fasting plasma glucose LS mean between-group difference of -16 mg/dL (95% CI, -26 to -6 mg/dL).
At 26 weeks, increase in LS mean total daily insulin dose was smaller in the lixisenatide group, while the percentage of participants requiring rescue therapy was both low and similar between groups (1.8% vs 2.3%, respectively).
The percentage of participants who experienced at least 1 hypoglycemic event was lower in the lixisenatide vs the BIAsp 30 group (odds ratio [OR], 0.62; 95% CI, 0.47-0.81). There was also a lower incidence of hypoglycemia in the lixisenatide group, which was observed across level 1 and 2 hypoglycemia categories.
Researchers found that hypoglycemia rates followed the same pattern as incidence, with an overall rate of any hypoglycemia in the lixisenatide group.
Three severe level 3 hypoglycemic episodes were reported: 1 in the lixisenatide and 2 in the BIAsp 30 group. There were lower incidence and event rates of level 2 nocturnal hypoglycemia (OR, 0.37; rate ratio, 0.28) in the lixisenatide group.
Over the 26-week treatment period, slightly more patients in the lixisenatide vs BIAsp 30 group experienced at least 1 adverse event (32.6% vs 27.7%, respectively); this difference was primarily attributed to the higher incidence of gastrointestinal events in the lixisenatide group (10.4% vs 2.3%, respectively). The most commonly reported adverse event was nausea (7.7% in lixisenatide) followed by nasopharyngitis (3.2% in BIAsp 30). The majority of adverse events were mild or moderate.
Severe adverse events were similar across groups — 2.7% vs 2.9%, respectively — with an overall low rate of treatment discontinuation in both groups of 0.9%.
Study limitations included the open-label design and the beginning of the COVID-19 pandemic during the final weeks of the study.
“[Lixisenatide] is an efficacious and well-tolerated regimen that is simpler for the patient, providing better glycemic control with weight benefit and less hypoglycemia compared with premix BIAsp 30 as an alternative for advancing therapy in people with type 2 diabetes previously suboptimally controlled with basal insulin plus [oral antihyperglycemic drugs],” the researchers concluded.
Disclosure: This clinical trial was supported by Sanofi. Please see the original reference for a full list of authors’ disclosures.
Rosenstock J, Emral R, Sauque-Reyna L, et al; for the SoliMix Trial Investigators. Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes: clinical outcomes with lixisenatide versus premix BIAsp 30 in the SoliMix randomized controlled trial. Diabetes Care. 2021;44:1-10. doi:10.2337/dc21-0393