Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled by Established Basal Insulin

Abstract

OBJECTIVETo examine the efficacy and safety of adding the once-daily glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide to established basal insulin therapy alone or together with metformin, in people with type 2 diabetes and elevated glycated hemoglobin (HbA1c).RESEARCH DESIGN AND METHODSWe conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20 μg or placebo for 24 weeks. Basal insulin dosage was unchanged except to limit hypoglycemia. HbA1c reduction from baseline was the primary end point.RESULTSMean duration of diabetes was 12.5 years, duration of insulin use was 3.1 years, insulin dosage was 55 units/day, and baseline HbA1c was 8.4%. With lixisenatide, the placebo-corrected change of HbA1c from baseline was –0.4% (95% CI –0.6 to –0.2; P = 0.0002), and mean HbA1c at end point was 7.8%. HbA1c <7.0% (53 mmol/mol) was attained by more lixisenatide (28%) than placebo (12%; P < 0.0001) participants. Lixisenatide reduced plasma glucose levels after a standardized breakfast (placebo-corrected reduction, –3.8 mmol/L; P < 0.0001); seven-point glucose profiles showed a reduction persisting through the day. Reductions in body weight (placebo corrected, –1.3 kg; P < 0.0001) and insulin dosage (–3.7 units/day; P = 0.012) were greater with lixisenatide. Main adverse events (AEs) with lixisenatide were gastrointestinal. Symptomatic hypoglycemia was 28% for lixisenatide and 22% for placebo; 4 of 328 subjects (1.2%) had severe hypoglycemia with lixisenatide vs. 0 of 167 with placebo.CONCLUSIONSBy improving HbA1c and postprandial hyperglycemia without weight gain in type 2 diabetes with inadequate glycemic control despite stable basal insulin, lixisenatide may provide an alternative to rapid-acting insulin or other treatment options.

Once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide is non‐inferior to once‐daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26‐week randomized phase III study

“…The incidence of antibodies in the present study was lower than in other GLP‐1 compounds with an exendin‐4 backbone (exenatide twice daily, 44–60% 32; exenatide once weekly, 61–68% 33, 34; and lixisenatide, approximately 70% 35); the lower incidence in the present study is probably attributable to the design of the dulaglutide molecule 36.…”

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

“…Lixisenatide was associated with a pronounced improvement in postprandial hyperglycaemia compared with placebo in these studies,25, 26, 27, 29 including studies in Asian patients exclusively 28, 30. Further, lixisenatide had a greater postprandial effect on blood glucose levels than the longer‐acting GLP‐1 receptor agonist liraglutide in patients with T2D insufficiently controlled on metformin, with or without insulin glargine 31, 32…”

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.…”