A better understanding of clinical characteristics of iGlarLixi vs. insulin glargine alone can lead to more effective therapy being implemented earlier, and fewer complications.
iGlarLixi is a once-daily, titratable, ﬁxed-ratio combination of insulin glargine 100 units/ ml (iGlar) and the GLP-1 receptor agonist lixisenatide (lixisenatide, 33 lg/ml). Two-phase three trials (LixiLan-L and LixiLan-O) have shown that the combination compared to either component alone has greater reductions in HbA1c and patients were more likely to achieve an HbA1c <7.0%. This post hoc study of the LixiLan-L trial analyzed baseline characteristics, glycemic control, and safety outcomes in participants who received the study-speciﬁed maximum dose (60 units/day) of iGlarLixi or iGlar vs. those who received <60 units/day.
The LixiLan-L trial was a phase 3, randomized, open-label, parallel-group study. Characteristics to meet eligibility criteria were: diagnosis of type 2 diabetes at least one year before screening, use of basal insulin for at least six months before screening, and had a stable basal insulin regimen with doses of 15 to 40 units/day (± 20%) for at least two months before the screening visit. After the run-in phase, participants who met the criteria of having an HbA1c between 7 to 10%, fasting plasma glucose <140, and an iGlar dose of 20 to 50 units/day were randomized in a 1:1 ratio to receive iGlarLixi or iGlar for 30 weeks.
The primary endpoint of this analysis was change in A1c from baseline to week 30. Secondary endpoints were fasting blood glucose, 2-hour postprandial glucose, body weight, the proportion of participants achieving A1C goal <7.0%, and the proportion of participants reaching A1C < 7.0% at week 30 with no weight gain or hypoglycemia. Safety endpoints included episodes of hypoglycemia, which included symptoms of hypoglycemia and a glucose level <70 mg/dl and incidences of G.I upset. After 30 weeks, 99 patients in the iGlarLixi group reached the max dose of 60 units/day compared to 112 patients in the iGlar group. Characteristics that favored the max dose were patients of younger ages, higher BMI, HbA1c, fasting plasma glucose, and insulin dose compared with participants at <60 units/day. The iGlar group had similar results for characteristics that favored the max dose with the addition of patients who had a shorter duration of diabetes. The only significant difference between dose groups was BMI, which was higher in the 60 units/day iGlarLixi group vs. 60 units/day iGlar group (33.8 vs. 32.3, respectively; p=0.0003).
The treatment outcomes of the study revealed that patients treated with iGlarLixi vs. iGlar in both dose groups showed signiﬁcantly greater reductions from baseline HbA1c [-1.2% vs. -0.6% in participants receiving <60 units/day and -1.0% vs. -0.5 in participants receiving 60 units/day, respectively (p<0.0001 for both)]. HbA1c reductions from baseline were similar regarding treatment doses. Final HbA1c levels were significantly lower with the iGlarLixi group vs. iGlar group for both dosing groups (<60 units/day p<0.0001; 60 units/day p=0.0003).
Final HbA1c levels were significantly lower in participants who received <60 units/day in both treatment groups (iGlarLixi p=0.0009; iGlar p=0.0169). More participants treated with iGlarLixi vs. iGlar in both dose groups achieved A1C <7.0% without weight gain or documented symptomatic hypoglycemia (60 units/day: p=0.0019; <60 units/day: p=0.0007). Change from baseline in 2-hour postprandial glucose was greater with iGlarLixi compared with iGlar in both dose groups (p<0.0001 for both comparisons). Participants treated with iGlarLixi in both dose groups showed a decrease in body weight at week 30 compared with a gain in participants in both iGlar dose groups (p=0.0003 for iGlarLixi 60 units/day vs. iGlar 60 units/day; p<0.0001 for iGlarLixi <60 units/day vs. iGlar <60 units/day). Fifteen percent of the iGlarLixi group reached the maximum dose without reaching target HbA1c levels compared to 23% for the iGlar group.
There was no signiﬁcant difference between the rate of documented symptomatic hypoglycemia between iGlarLixi and iGlar in either dose group. Overall, fewer participants experienced GI adverse events in the iGlar group compared with those in the iGlarLixi group (4.7% vs. 12.8% in the <60 units/day group, respectively; p=0.0017; 0.9% vs. 11.1% in the 60 units/day group, respectively; p=0.0016). The hypothesis that the combination therapy of iGlarLixi would be more effective than iGlar alone was true.
- Baseline characteristics that were significant predictors of patients reaching 60 units/day were basal insulin dose, BMI, age, and fasting blood glucose.
- iGlarLixi is more effective at reducing the HbA1c to <7.0% than iGlar.
- Episodes of hypoglycemia were not significantly different for each treatment group regardless of the dosage.
Blonde L, Bailey TS, Chao J, Dex TA, Frias JP, Meneghini LF, Roberts M, Aroda VR. Clinical Characteristics and Glycemic Outcomes of Patients with Type 2 Diabetes Requiring Maximum Dose Insulin Glargine/Lixisenatide Fixed-Ratio Combination or Insulin Glargine in the LixiLan-L Trial. Adv Ther. 2019 Sep;36(9):2310-2326.
Antonio Bess, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy