Efficacy and Safety of Lixisenatide Once Daily Versus Exenatide Twice Daily in Type 2 Diabetes Inadequately Controlled on Metformin: A 24-week, randomized, open-label, active-controlled study (GetGoal-X) (original) (raw)
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Diabetes Care, 2013
OBJECTIVE To compare efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled with metformin. RESEARCH DESIGN AND METHODS Adults with diabetes inadequately controlled (HbA1c 7–10%) with metformin were randomized to lixisenatide 20 μg once daily (n = 318) or exenatide 10 μg twice daily (n = 316) in a 24-week (main period), open-label, parallel-group, multicenter study. The primary objective was a noninferiority assessment of lixisenatide versus exenatide in HbA1c change from baseline to week 24. RESULTS Lixisenatide once daily demonstrated noninferiority in HbA1c reduction versus exenatide twice daily. The least squares mean change was −0.79% (mean decrease 7.97 to 7.17%) for lixisenatide versus −0.96% (mean decrease 7.96 to 7.01%) for exenatide, and treatment difference was 0.17% (95% CI, 0.033–0.297), meeting a predefined noninferiority upper CI margin of 0.4%. Responder rate (HbA1c <7.0%) and improvements in fasting ...
ABSTRACT Aims/IntroductionThis was a subanalysis of Japanese patients included in the glucagon-like peptide-1 receptor agonist AVE0010 in patients with type 2 diabetes mellitus for glycemic control and safety evaluation (GetGoal-S) study – a 24-week, randomized, placebo-controlled study of lixisenatide in patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin.Materials and Methods In GetGoal-S, 127 Japanese patients received the once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide 20 μg/day or a matching placebo. The primary outcome was change in glycated hemoglobin.ResultsAt week 24, lixisenatide significantly reduced mean glycated hemoglobin (least squares mean difference vs the placebo −1.1% [12 mmol/mol, P < 0.0001]), and significantly more lixisenatide patients reached glycated hemoglobin targets of <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) vs the placebo. Lixisenatide produced statistically significant reductions in 2-h postprandial plasma glucose (least squares mean difference vs the placebo −8.51 mmol/L, P < 0.0001) and glucose excursion vs the placebo, and significantly reduced fasting plasma glucose (least squares mean difference vs the placebo −0.65 mmol/L, P = 0.0454). Bodyweight decreased with both lixisenatide and the placebo (least squares mean change −1.12 kg for lixisenatide, −1.02 kg for placebo). The overall incidence of adverse events was similar for lixisenatide and the placebo (84.2 and 82.4%, respectively), the most frequent being gastrointestinal disorders (52.6% for lixisenatide vs 29.4% for placebo). The incidence of symptomatic hypoglycemia was higher with lixisenatide vs the placebo (17.1 and 9.8%, respectively), with no cases of severe symptomatic hypoglycemia in either group.Conclusions In the Japanese subpopulation of the GetGoal-S study, lixisenatide produced a significant and clinically relevant improvement in glycated hemoglobin, with a pronounced improvement in postprandial plasma glucose, and a good safety and tolerability profile
2013
OBJECTIVEdTo examine the efficacy and safety of lixisenatide (20 mg once daily, adminis-tered before the morning or evening meal) as add-on therapy in patients with type 2 diabetes insufficiently controlled with metformin alone. RESEARCH DESIGN AND METHODSdThis was a 24-week, randomized, double-blind, placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes (HbA1c 7–10 % [53286 mmol/mol]). Patients were randomized to lixisenatide morning (n = 255), lixisenatide evening (n = 255), placebo morning (n = 85), or placebo evening (n = 85) injections. RESULTSdLixisenatide morning injection significantly reduced mean HbA1c versus com-bined placebo (mean change20.9 % [9.8 mmol/mol] vs.20.4 % [4.4 mmol/mol]; least squares [LS] mean difference vs. placebo20.5 % [5.5 mmol/mol], P, 0.0001). HbA1c was significantly reduced by lixisenatide evening injection (mean change –0.8 % [8.7 mmol/mol] vs. –0.4 % [4.4 mmol/mol]; LS mean difference –0.4 % [4.4 mmol/mol], P, 0.0001...
Background and objectives: Lixisenatide, a selective short-acting glucagon-like peptide 1?receptor agonist (GLP-1RAs), approved in many countries worldwidefor use with oral glucose-lowering agents with or without basal insulin for the treatment of adults with uncontrolled type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise. The aim of this study was to assess the effectiveness of basal insulin treatmentregimen intensification with Lixisenatide compared with another injectable drugin patients with T2DM. We also aimed to identify the respective predictive factors for glycemic control. Materials and Methods: This prospective, multi-center, non-controlled observational study included 242 patients with T2DMuncontrolled on their current antidiabetic treatmentwith insulin therapy receiving a GLP-1RAs(122 patients received Lixisenatide and 120 patients received other intensification drugs). The primary endpoints were the change in postprandial glucose (PPG), Fasting plasma glucose (FPG) and HbA1c after three and six months. The patient was considered responder (or at target) if theHbA1c was <7% with nosymptomatic hypoglycemic episode inthe previousthree months and no weight gain since the initiation of intensification therapy. Results: We reported a statistically significant reduction(p<0.001) in HbA1c, FPG,and PPG levels after three and six months on Lixisenatide based treatment. These results did not differ significantly from the other intensification therapy while,a significantdecrease in body weight was observed inLixisenatide group (91.9 to 87.9 kg,p<0.001)compared with other intensification therapy group (83.1 to 82 kg, p=0.605). About 12% of patients in Lixisenatide group and 8.4% of patients in other intensification achieved the target HbA1c <7% after three months of intensification therapy, with no statistically significant differences between the two groups (P=0.26).While after six months of intensification therapy, 36.8% in Lixisenatide group and36.1% in other intensification group achieved thetarget HbA1c <7%, with no statistically significant differences between the two groups (P=0.921). The targeted HbA1c <7% with no symptomatic hypoglycemic episode after three months of intensification therapy and no weight gain was achieved by 11.1% of patients in Lixisenatidegroup compared with 8.4% of patientsin the other intensification therapy group, p=0.26. The safety profile of Lixisenatide, including rates of nausea and vomiting, wasconsistent with that observed in other Lixisenatide therapies. Hypoglycemic events were less in Lixisenatidecompared with other intensification therapy(1.6% versus 6.9%, p=0.03). HbA1c at baseline, regular healthy diet plan,and duration of diabetes were the most significant predictors for the patients? response. Conclusion: The use of Lixisenatide in combination with basal insulin represents an effective and well-tolerable treatment for patients with T2DM, with improvements in glycemic control, reducing body weight or preventing weight gain, with low risk of hypoglycemia.
Aims: This 76-week, open-label, parallel-group study assessed the long-term safety of once-daily lixisenatide monotherapy in Japanese patients with type 2 diabetes mellitus. Methods: Patients were randomized to receive lixisenatide in a 2-step or a 1-step dose-increase regimen. The primary objective was to assess the safety of lixisenatide at week 24 by a descriptive comparison of the 2-and 1-step groups. Results: As expected with treatment with a glucagon-like peptide-1 agonist, nausea was the most common treatment-emergent adverse event (2-step group: n = 12/33 [36.4%] vs 1-step group: n = 18/36 [50.0%] up to week 24). In total, 5/33 patients (15.2%; 2-step group) and 2/36 patients (5.6%; 1-step group) prematurely discontinued treatment up to week 24, mainly due to adverse events. Serious treatment-emergent adverse events occurred in 2/33 patients (6.1%; 2-step group) versus 0/36 patients (0%; 1-step group) up to week 24. Symptomatic hypoglycemia occurred in 2/33 patients (6.1%; 2-step group) versus 1/36 patients (2.8%; 1-step group) up to week 24, with no severe events reported. Glycated hemoglobin, fasting plasma glucose, and body weight were reduced from baseline at weeks 24 and 76. Conclusion: In Japanese patients with type 2 diabetes mellitus, once-daily lixisenatide monotherapy was well tolerated, with less nausea with the 2-step regimen.
Diabetic Medicine, 2010
AimsTo evaluate the dose–response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes.MethodsRandomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) ≥ 7.0 and < 9.0% (≥ 53 and < 75 mmol/mol)] on metformin (≥ 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 μg once daily or twice daily or placebo. The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population.ResultsLixisenatide significantly improved mean HbA1c from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 μg doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P< 0.01 vs. placebo). Target HbA1c < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 μg once-daily lixisenatide vs. 32% receiving placebo (P< 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from −2.0 to −3.9 kg with lixisenatide vs. −1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea.ConclusionsLixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose–response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 μg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies.
Efficacy and safety of lixisenatide in patients with type 2 diabetes and renal impairment
Diabetes, obesity & metabolism, 2017
This post hoc assessment evaluated the efficacy and safety of once-daily, prandial glucagon-like peptide-1 receptor agonist lixisenatide in patients with type 2 diabetes (T2D) and normal renal function (estimated glomerular filtration rate ≥90 mL/min), or mild (60-89 mL/min) or moderate (30-59 mL/min) renal impairment. Patients from 9 lixisenatide trials in the GetGoal clinical trial programme were categorized by baseline creatinine clearance: normal renal function (lixisenatide n = 2094, placebo n = 1150); renal impairment (mild: lixisenatide n = 637, placebo n = 414; moderate: lixisenatide n = 122, placebo n = 68). Meta-analyses of placebo-adjusted mean differences between baseline renal categories were performed for efficacy and safety outcomes. HbA1c, 2-hour postprandial plasma glucose and fasting plasma glucose were comparably reduced in lixisenatide-treated patients with normal renal function, and mild and moderate renal impairment. The most common adverse events (AEs) in all ...