Safety, tolerability and efficacy of lixisenatide as monotherapy in Japanese patients with type 2 diabetes mellitus: An open‐label, multicenter study

Abstract

Aim/IntroductionTo assess the overall safety of lixisenatide monotherapy in Japanese patients with type 2 diabetes mellitus.Materials and MethodsPatients with type 2 diabetes mellitus, previously treated with ≤1 oral antidiabetic drug, were enrolled in an uncontrolled, open‐label, single‐arm study over 24 and 52 weeks. Any oral antidiabetic drug treatment was stopped at the start of the 6‐week run‐in period. From baseline, patients received once‐daily lixisenatide monotherapy (10 μg for 1 week, 15 μg for 1 week, 20 μg thereafter) for 52 weeks (first 140 patients enrolled) or 24 weeks (subsequently enrolled patients). The primary end‐point was safety over 24 and 52 weeks. Secondary efficacy end‐points included absolute change in glycated hemoglobin, fasting plasma glucose and bodyweight from baseline.ResultsOf 428 patients screened, 361 and 140 were treated for 24 and 52 weeks, respectively; 88.4 and 90.0% completed treatment. During the 24‐ and 52‐week treatment periods, 268/361 (74.2%) and 117/140 (83.6%) patients, respectively, had treatment‐emergent adverse events; the most frequently reported was nausea (33.2 and 31.4%, respectively). The risk of severe hypoglycemia was low; only one case was reported. Lixisenatide treatment resulted in a decrease in mean glycated hemoglobin A1c (−0.98 and −0.86%), fasting plasma glucose (−1.05 and −0.85 mmol/L), and bodyweight (−1.33 and −1.48 kg) for the 24‐ and 52‐week treatment periods, respectively.ConclusionsOnce‐daily lixisenatide monotherapy was associated with a safety profile in line with the glucagon‐like peptide‐1 receptor agonist class, and improved glycemic control in Japanese patients with type 2 diabetes mellitus.

Clinical factors associated with the occurrence of nausea and vomiting in type 2 diabetes patients treated with glucagon‐like peptide‐1 receptor agonists

“…The incidence of nausea/vomiting in the present study was consistent with some previous studies of Japanese patients treated with lixisenatide. However, in patients treated with liraglutide, the present study showed a high incidence of nausea/vomiting compared with previous studies in which the occurrence of GI AEs was reported to be 44–60%, of which nausea occurred in 5–14%.…”

Efficacy and safety of polyethylene glycol loxenatide as add‐on to metformin in patients with type 2 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled, phase 3b trial

“…A clinical trial on lixisenatide showed that there were no clinically meaningful changes in lipid variables during the 24-and 52-week treatment periods. 31 A post hoc analysis of the SUSTAIN trials revealed that semaglutide was associated with minor reductions or no change in lipid levels across all race and ethnicity subgroups in the SUSTAIN 1 to 7 trials. 32 However, clinical trials on exenatide showed that treatment with exenatide twice-daily or once-weekly significantly improved lipids in Asian and white patients.…”

“…Our results were consistent with some other studies of GLP‐1 RAs. A clinical trial on lixisenatide showed that there were no clinically meaningful changes in lipid variables during the 24‐ and 52‐week treatment periods 31 . A post hoc analysis of the SUSTAIN trials revealed that semaglutide was associated with minor reductions or no change in lipid levels across all race and ethnicity subgroups in the SUSTAIN 1 to 7 trials 32 .…”

Efficacy and safety of insulin glargine/lixisenatide fixed‐ratio combination (iGlarLixi 1:1) in Japanese patients with type 2 diabetes mellitus inadequately controlled on oral antidiabetic drugs: A randomized, 26‐week, open‐label, multicentre study: The LixiLan JP‐O2 randomized clinical trial

“…Nausea was reported in 1.9% of iGlar patients and 9.6% of iGlarLixi patients, which is still less than commonly reported for lixisenatide alone. 8,18 These favourable findings are most probably related to the gradual dose increase by 1 U/1 μg from the starting dose of 5 U/5 μg. The high completion rates for the 26-week treatment period (95.4% and 97.3%) in this study show that these events were not severe enough to influence the overall tolerability of treatment.…”