Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal‐P)

Abstract

Aims:To compare the efficacy and safety of once-daily prandial lixisenatide with placebo in type 2 diabetes mellitus (T2DM) insufficiently controlled by pioglitazone ± metformin. Methods:This randomized, double-blind study included a 24-week main treatment period and a ≥52-week variable extension period.Patients were randomized 2 : 1 to receive lixisenatide 20 μg once daily or placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) at week 24. Results:In total, 484 patients were randomized: 323 to lixisenatide; 161 to placebo. After 24 weeks, lixisenatide once daily significantly improved HbA1c (−0.56% vs. placebo; p < 0.0001) and increased the proportion of patients achieving HbA1c <7% compared with placebo (52.3% vs. 26.4%, respectively; p < 0.0001) and significantly improved fasting plasma glucose (−0.84 mmol/l vs. placebo; p < 0.0001). There was a small decrease in body weight with lixisenatide once daily and a small increase with placebo, with no statistically significant difference between the two groups. Overall, lixisenatide once daily was well tolerated, with a similar proportion of treatment-emergent adverse events (TEAEs) and serious TEAEs between groups (lixisenatide: 72.4% and 2.5%; placebo: 72.7% and 1.9%). Symptomatic hypoglycaemia rates were also relatively low in both groups (lixisenatide 3.4% and placebo 1.2%), with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable extension period. Conclusions:Lixisenatide once daily significantly improved glycaemic control with a low risk of hypoglycaemia, and was well tolerated over 24 weeks and during the long-term, double-blind extension period in patients with T2DM insufficiently controlled on pioglitazone ± metformin.

Adverse Effects of GLP-1 Receptor Agonists

“…The combination of GLP-1 receptor agonists and metformin has not been associated with an increase in the rate or severity of clinically relevant hypoglycemic events [32,34,45,46,[115][116][117][118][119][120][121][122]. However, in clinical trials examining GLP-1 receptor agonists in combination with sulphonylurea (with or without metformin) or insulin, the incidence of hypoglycemia, although low overall, was increased compared with placebo ( Table 6, in the Appendix) [32,33,42,[123][124][125][126][127][128][129][130][131][132][133][134][135].…”

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

“…Lixisenatide (Lyxumia ® , Adlyxin ® ; Sanofi, Paris, France) is a once‐daily (QD), prandial, short‐acting GLP‐1 RA that has been evaluated extensively in the large, phase 3 GetGoal clinical trial program carried out in approximately 50 countries including Japan11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21. Treatment with lixisenatide monotherapy in patients with type 2 diabetes mellitus has shown improved glycemic control with reduced HbA1c, postprandial plasma glucose, fasting plasma glucose (FPG) and bodyweight, and has been shown to be well tolerated11, 12, 13.…”

“…Treatment with lixisenatide monotherapy in patients with type 2 diabetes mellitus has shown improved glycemic control with reduced HbA1c, postprandial plasma glucose, fasting plasma glucose (FPG) and bodyweight, and has been shown to be well tolerated11, 12, 13. Lixisenatide has also shown improved glycemic control as an add‐on treatment (including basal insulin with or without SU, metformin, metformin with or without SU, pioglitazone with or without metformin, and SU with or without metformin)12, 14, 15, 16, 17, 18, 19. More specifically, subanalyses of two randomized, placebo‐controlled studies in patients with type 2 diabetes mellitus, GetGoal‐S12 (lixisenatide add‐on to SU with or without metformin) and GetGoal‐L‐Asia (lixisenatide add‐on to basal insulin with or without SU)14, showed that lixisenatide treatment provided glycemic control (decreased HbA1c, FPG and postprandial plasma glucose), and was well tolerated in the Japanese subpopulation22, 23.…”

Lixisenatide

“…1,2 Lixisenatide has been studied as monotherapy and in combination with other antidiabetic medications or with basal insulin. 1,[3][4][5][6][7][8][9][10][11][12] The other US Food and Drug Administration (FDA)-approved GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide immediate-release injection, exenatide extended-release injection, and liraglutide) are also indicated as adjunctive therapies to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Each agent has been studied for use as monotherapy and in combination with other antidiabetic medications; however, the current labeling for each advises that these agents are not recommended as first-line therapy for patients inadequately controlled on diet and exercise.…”