Efficacy and Safety of 1:1 Fixed-Ratio Combination of Insulin Glargine and Lixisenatide Versus Lixisenatide in Japanese Patients With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetic Drugs: The LixiLan JP-O1 Randomized Clinical Trial

Hirotaka Watada, Akane Takami, Robert Spranger, Atsushi Amano, Yasuhiro Hashimoto, Elisabeth Niemoeller, Hirotaka Watada, Akane Takami, Robert Spranger, Atsushi Amano, Yasuhiro Hashimoto, Elisabeth Niemoeller

Abstract

Objective: To assess the efficacy and safety of a 1:1 fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) versus lixisenatide (Lixi) in insulin-naive Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs).

Research design and methods: In this phase 3, open-label, multicenter trial, 321 patients with HbA1c≥7.5 to ≤10.0% (58-86 mmol/mol) and fasting plasma glucose (FPG) ≤13.8 mmol/L (250 mg/dL) were randomized 1:1 to iGlarLixi or Lixi for 52 weeks. The primary end point was change in HbA1c at week 26.

Results: Change in HbA1c from baseline to week 26 was significantly greater with iGlarLixi (-1.58% [-17.3 mmol/mol]) than with Lixi (-0.51% [-5.6 mmol/mol]), confirming the superiority of iGlarLixi (least squares [LS] mean difference -1.07% [-11.7 mmol/mol], P < 0.0001). At week 26, significantly greater proportions of patients treated with iGlarLixi reached HbA1c <7% (53 mmol/mol) (65.2% vs. 19.4%; P < 0.0001), and FPG reductions were greater with iGlarLixi than Lixi (LS mean difference -2.29 mmol/L [-41.23 mg/dL], P < 0.0001). Incidence of documented symptomatic hypoglycemia (≤3.9 mmol/L [70 mg/dL]) was higher with iGlarLixi (13.0% vs. 2.5%) through week 26, with no severe hypoglycemic events in either group. Incidence of gastrointestinal events through week 52 was lower with iGlarLixi (36.0% vs. 50.0%), and rates of treatment-emergent adverse events were similar.

Conclusions: This phase 3 study demonstrated superior glycemic control and fewer gastrointestinal adverse events with iGlarLixi than with Lixi, which may support it as a new treatment option for Japanese patients with T2DM that is inadequately controlled with OADs.

Trial registration: ClinicalTrials.gov NCT02749890.

© 2020 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Efficacy end points. A: Total difference in HbA1c after 26 weeks of treatment; HbA1c (%) outside the parentheses, HbA1c (mmol/mol) inside the parentheses for LS mean change from baseline, LS mean difference between the two groups, and 95% CI. B: Time course of change in HbA1c throughout the 52-week treatment period. Values are presented as mean ± SE. C: Percentage of patients achieving HbA1c <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) in the 26-week treatment period. D: Change in FPG in the first 26-week treatment period. E: Changes in seven-point SMPG profile in the 26-week treatment period.

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Source: PubMed

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