Efficacy and Safety of 1:1 Fixed Ratio Combination of Insulin Glargine/Lixisenatide (iGlarLixi) versus Lixisenatide in Japanese Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Oral Antidiabetic Drugs: The LixiLan JP-O1 Randomized Clinical Trial

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-naïve Japanese patients with type 2 diabetes mellitus 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 to 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 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%); 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 type 2 diabetes inadequately controlled on OADs.</p

The distribution of the department after matching for age, sex and specific type of surgery.

The distribution of the department after matching for age, sex and specific type of surgery.</p

The time periods in the operating room for three common and standardized surgeries before and after JCI accreditation.

The time periods in the operating room for three common and standardized surgeries before and after JCI accreditation.</p

The glossary of time periods in the operating room.

The glossary of time periods was divided into five time intervals. (A). preAT = pre-anesthesia time, (B). AIT = anesthesia induction time, (C). PT = procedure/surgery time, (D). AAT = anesthesia awareness time, (E). postAT = post-anesthesia time, prePT = pre-procedure/surgery time (A+B), postPT = post-procedure/surgery time (C+D), TPT = total procedure/surgery time (prePT+C+postPT), PIR = patient in room, AI = anesthesia induction, PS = position/prep start, PST = procedure/surgery start time, PF = procedure/surgery finish time, AA = anesthesia awareness, AF = anesthesia finish time, POR = patient out of room.</p

Characteristics of patients before and after matching for age, sex and specific type of surgery.

Characteristics of patients before and after matching for age, sex and specific type of surgery.</p

The flow diagram.

A total of 13,288 patients were included in this study. Of the 8,835 and 4,453 patients receiving surgery before and after JCI accreditation, 3,222 pairs were matched for age (every 10 years), sex, and specific type of surgery. JCI = Joint Commission International.</p

Time periods in the operating room between matched patients before and after JCI accreditation.

Time periods in the operating room between matched patients before and after JCI accreditation.</p

A representative case of coronary artery ectasia.

Images of a 62-year-old man with an abdominal aortic aneurysm. Diffuse ectasia and focal stenosis in the right coronary artery are seen (A). The axial image (B) and 3D reconstruction image (C) of computed tomography show an infra-renal aortic aneurysm.</p

The parameter assessment of ectatic coronary arteries.

The dotted lines show the range analysed in the left anterior descending artery (A), left circumflex artery (B), and right coronary artery (C), respectively. Abbreviations: D1, maximal diameter; D2, minimal diameter.</p

Qualitative and quantitative coronary angiography findings.

Qualitative and quantitative coronary angiography findings.</p