Lixisenatide In Patients Research Articles

Эффективность и безопасность фиксированной комбинации инсулина гларгин 100 ЕД/мл и ликсисенатида для больных сахарным диабетом 2 типа в зависимости от возраста пациентов и исходного HbA1C в исследовании SOLO

Эффективность и безопасность фиксированной комбинации инсулина гларгин 100 ЕД/мл и ликсисенатида для больных сахарным диабетом 2 типа в зависимости от возраста пациентов и исходного HbA1C в исследовании SOLO

Применение фиксированной комбинации инсулина гларгин 100 ЕД/мл и ликсисенатида пациентами с сахарным диабетом 2 типа в реальной клинической практике. Собственные наблюдения

Применение фиксированной комбинации инсулина гларгин 100 ЕД/мл и ликсисенатида пациентами с сахарным диабетом 2 типа в реальной клинической практике. Собственные наблюдения

Опыт применения фиксированной комбинации инсулина гларгин 100 ЕД/мл и ликсисенатида у пациентов с СД 2 типа, не достигших целевых показателей при применении пероральных cахароснижающих препаратов

Опыт применения фиксированной комбинации инсулина гларгин 100 ЕД/мл и ликсисенатида у пациентов с СД 2 типа, не достигших целевых показателей при применении пероральных cахароснижающих препаратов

1134-P: Efficacy of iGlarLixi in Adults with Type 2 Diabetes Inadequately Controlled on Two or More Oral Antidiabetic Agents

LixiLan-O, a randomized, 30-week, open-label study compared the fixed-ratio combination of insulin glargine/lixisenatide (iGlarLixi) with insulin glargine (iGlar) or lixisenatide in patients inadequately controlled on metformin alone or combined with a second OAD. This exploratory subgroup analysis examines the efficacy and safety of iGlarLixi vs. iGlar in patients with baseline HbA1c ≥8.0% receiving metformin plus a second OAD at screening; the second OAD was a sulfonylurea in 93.8% of patients. Mean age was 59.2 years, mean BMI was 31.5 kg/m2, mean diabetes duration was 10.0 years, and mean duration of second OAD use was 4.5 years. Compared with iGlar alone, the iGlarLixi-treated group demonstrated greater mean reductions from baseline in HbA1c, 2-h PPG, and weight, greater proportions achieving HbA1c <7.0%, or a composite endpoint of HbA1c <7.0% with no weight gain (Table). There were no differences between the groups in change in FPG, or in insulin dose at Week 30 (40.7 vs. 40.2 U/day, respectively; p=0.8664). Incidences of documented symptomatic hypoglycemia (plasma glucose ≤70 mg/dL) were similar between groups (29.0% and 27.9%, respectively). Patients in this difficult-to-treat subgroup with advanced T2D and higher baseline HbA1c achieved better glycemic control without increased risk of hypoglycemia when intensified with iGlarLixi compared with iGlar. Disclosure N. Skolnik: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Mylan, Sanofi, Teva Pharmaceutical Industries Ltd. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoSmithKline plc., Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. E. Niemoeller: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. E. Souhami: Employee; Self; Sanofi Research & Development. L. Meneghini: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Sanofi-Aventis. Consultant; Self; Sanofi-Aventis. Other Relationship; Self; American Diabetes Association. Funding Sanofi

Cost-effectiveness of once-weekly semaglutide versus dulaglutide and lixisenatide in patients with type 2 diabetes with inadequate glycemic control in Sweden

Aims: This analysis evaluated the cost-effectiveness of once-weekly semaglutide vs glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) uncontrolled on metformin or basal insulin in Sweden.Materials and methods: This cost-effectiveness analysis (CEA) was conducted using the Swedish Institute of Health Economics (IHE) Diabetes Cohort Model. Analyses were conducted from the Swedish societal perspective over a time horizon of 40 years. For patients uncontrolled on metformin, dulaglutide was the comparator, and data from the SUSTAIN 7 clinical trial was used. For patients uncontrolled on basal insulin, lixisenatide was chosen as the comparator and data was obtained from a network meta-analysis (NMA).Results: The results show that, in patients with inadequate control on metformin, semaglutide 1.0 mg dominated (i.e. provided greater clinical benefit, and was less costly) dulaglutide 1.5 mg. In patients with inadequate control on basal insulin, semaglutide 1.0 mg dominated lixisenatide. The reduction in costs is largely driven by the reduction in complications seen with once-weekly semaglutide.Limitations and conclusions: It is likely that this analysis is conservative in estimating the cardiovascular (CV) cost benefits associated with treatment with once-weekly semaglutide. In patients inadequately controlled on basal insulin, the analyses vs lixisenatide were based on results from an NMA, as no head-to-head clinical trial has been conducted for this comparison. These CEA results show that once-weekly semaglutide is a cost-effective GLP-1 RA therapy for the treatment of T2D in patients inadequately controlled on metformin or basal insulin, addressing many current clinician, patient, and payer unmet needs in Sweden.

PRISMA-efficacy and safety of lixisenatide for type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

We aimed to systematically evaluate the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus. PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Google, Web of Science and the Chinese Science Citation Database were searched up to March 2018. Randomized controlled trials determining the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus were eligible for inclusion. Two authors independently extracted the data in a prespecified Microsoft Excel spreadsheet. A meta-analysis was performed using Review Manager 5.3 software. Weighted mean difference (WMD) and relative risk (RR) together with their corresponding 95% confidence intervals (CIs) were estimated, and only the random effects model was used in order to achieve a more conservative estimate of the efficacy and safety. Fourteen multicenter randomized controlled trials involving 11,947 patients were eligible for inclusion. Compared to placebo, lixisenatide could more significantly reduce the level of HbA1c (WMD=-0.44; 95% confidence interval [CI] [-0.55,-0.33]), and a higher proportion of lixisenatide-treated patients achieved the HbA1c level of < 7.0% (RR = 1.89, 95% CI [1.75-2.03]) and < 6.5% (RR = 3.03, 95% CI [2.54-3.63]) than the placebo-treated patients. Lixisenatide was also associated with a significant reduction in fasting plasma glucose and 2-hour postprandial plasma glucose levels. The risks for any adverse events, gastrointestinal adverse events, and symptomatic hypoglycemia significantly increased in the lixisenatide-treatedment group compared to those in the placebo group. However, lixisenatideit did not increase the risks of serious adverse events, death, or severe hypoglycemia. Lixisenatide was more effective than placebo in patients with type 2 diabetes mellitus, and the mild-to-moderate adverse events were found to be tolerated during the follow-up.

Intensification of Basal Insulin Therapy with Lixisenatide in Patients with Type 2 Diabetes in a Real-World Setting: The BASAL-LIXI Study

Basal insulin reduces fasting blood glucose levels, but postprandial blood glucose levels may remain higher. Traditional strategies with rapid insulin intensification can cause hypoglycemic episodes and weight gain. Glucagon-like peptide-1 receptor agonists, such as the short-acting lixisenatide, are able to control postprandial excursions, without weight gain, and with a low risk of hypoglycemic events. Due to the limited data on the combination of lixisenatide with basal insulin (with or without oral antidiabetes drugs) in clinical practice, this study evaluated changes in parameters associated with glycemic control and anthropometric data after 24 weeks of this therapy intensification. This was a multicenter, retrospective observational study of 129 patients with type 2 diabetes that was uncontrolled by basal insulin. Their treatment was intensified by the addition of lixisenatide at least 24 weeks before being included in the study. Data were retrospectively collected to determine changes in glycated hemoglobin (HbA1c) levels, blood glucose levels, weight, and body mass index. Adverse reactions and hypoglycemic events were also recorded. After 24 weeks of therapy intensification with lixisenatide, a significant reduction in HbA1c levels was observed (-1.1%; P < 0.001). An HbA1c <7% was achieved in 30.2% of patients, and 17.1% reached an HbA1c <6.5%. There was a reduction in fasting blood glucose (31.8 [60.3] mg/dL; P < 0.001) and postprandial blood glucose (55.0 [49] mg/dL; P < 0.001) levels, as well as body weight (4.0 [5.4] kg; P < 0.001) and body mass index (1.5 [1.9]; P < 0.001). The most commonly observed adverse reactions were nausea (n = 9), in line with previous studies. Hypoglycemia events were rare; only reported in 2 patients. Intensification strategy based on lixisenatide added to basal insulin (with or without oral antidiabetes drugs) can be an effective treatment option in patients with uncontrolled type 2 diabetes. In this small, selected population, glycemic control was significantly improved in terms of HbA1, fasting blood glucose levels, and postprandial glucose levels, with a reduction of body weight and low risk of hypoglycemic events. (Curr Ther Res Clin Exp. 2018; 79:XXX-XXX).

Lixisenatide, a Once-Daily Prandial Glucagon-Like Peptide-1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes.

Lixisenatide, a short-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), has been available in Europe since 2013 and was recently approved in the United States for the treatment of type 2 diabetes (T2D) as an adjunct to diet and exercise. The objective of this systematic review is to describe the pharmacology, pharmacokinetics, safety, and efficacy of lixisenatide in patients with T2D. We conducted a search of the EMBASE database, limited to human studies with abstracts available in English. Published conference abstracts, limited to the American Diabetes Association (ADA) and the European Association for the Study of Diabetes meetings in 2015, as well as abstracts presented at the ADA meeting in 2016, were also screened. The abstracts retrieved were assessed for relevance; review articles and meta-analyses focusing on GLP-1 RAs as a class were excluded. Lixisenatide induced mean reductions of 0.46-0.99% in glycated hemoglobin A1c (HbA1c ), 55.86-143.43mg/dl in 2-hour postprandial glucose (PPG) levels, and 56.58-127.75mg/dl in mealtime glucose level variations. Changes in fasting plasma glucose (FPG) levels and weight ranged from -21.98 to +5.41mg/dl and from -2.96 to +0.3kg, respectively, in patients with T2D enrolled in the GetGoal clinical program (a program of clinical trials that established the efficacy and safety profile of lixisenatide 20μg once/day across patients with T2D with differing background therapies). Lixisenatide was well tolerated, demonstrating rates of symptomatic hypoglycemia of 0.8-42.9% and a very low rate of severe hypoglycemia (<1.5%) as well as no increased risk of cardiovascular events. The most common adverse events were gastrointestinal in nature, mainly transient nausea and vomiting of mild-to-moderate severity. Lixisenatide effectively lowers HbA1c levels in patients with T2D through a mechanism of action complementary to that of agents that mainly target FPG, with the additional benefit of weight loss. Its once-daily administration schedule and effect on PPG levels make it an attractive option as add-on treatment to basal insulin therapy or oral antidiabetic agents.

Efficacy and safety of lixisenatide in patients with type 2 diabetes and renal impairment.

AimsThis 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.MethodsPatients 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.Results 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 renal function categories were gastrointestinal (GI), predominantly nausea and vomiting. A 14% higher incidence of GI AEs and a 10% higher incidence of nausea and vomiting were seen with mild impairment vs normal function (P = .003 for both), but no significant differences were observed between the mild and moderate impairment categories (P = .99 and P = .57, respectively), or between the moderate impairment and normal categories (P = .16 and P = .65, respectively). Additionally, the incidence of hypoglycaemia was similar in all categories.ConclusionsThis study demonstrates that baseline renal status does not affect efficacy outcomes in lixisenatide‐ vs placebo‐treated patients, and that no lixisenatide dose adjustment is required for patients with T2D with mild or moderate renal impairment.

Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse β-cell function in the GetGoal-M and GetGoal-S trials

AimsTo evaluate the impact of β-cell function on the efficacy of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes (T2D). Materials and methodsIn this post hoc analysis, patients from the Phase 3 GetGoal-M and GetGoal-S clinical trials randomized to lixisenatide 20μg once daily were stratified into quartiles by baseline β-cell function, as measured by the secretory units of islet in transplantation (SUIT) index. ResultsPatients (N=437) were distributed evenly among SUIT index quartiles 1 to 4 (lowest to highest β-cell function). Clinical outcomes improved from baseline across all SUIT quartiles; mean changes at week 24 were: glycated hemoglobin (HbA1c; % [mmol/mol]), −0.99 (−10.8), −0.87 (−9.5), −0.86 (−9.4), −0.83 (−9.1); and postprandial plasma glucose (PPG; mmol/L), −7.9, −5.6, −5.5, −4.3 (overall effect P<0.0001). Furthermore, postprandial glucagon was reduced in all SUIT quartiles, while insulinogenic index improved only in patients with higher baseline SUIT (overall effect P=0.0286). No severe symptomatic hypoglycemic events were reported. ConclusionsLixisenatide treatment resulted in reductions in HbA1c and PPG levels across all SUIT quartiles. This suggests that non-insulin-related actions of lixisenatide contribute to improved glycemic control in T2D.

Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome

Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1–receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.

Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome

BackgroundCardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1–receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.MethodsWe randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina.ResultsThe 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81). There were no significant between-group differences in the rate of hospitalization for heart failure (hazard ratio in the lixisenatide group, 0.96; 95% CI, 0.75 to 1.23) or the rate of death (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than was placebo.ConclusionsIn patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.)

Combination therapy of glucagon-like peptide-1 receptor agonists and insulin for patients who developed diabetes after partial pancreatectomy.

Aims/IntroductionIt is known that after pancreatectomy, patients experience hyposecretion of endogenous insulin and frequently develop diabetes. However, it has been unclear whether combination therapy with glucagon‐like peptide‐1 receptor agonists and basal insulin is effective for such patients. In the present study, we evaluated the efficacy and safety of combination therapy with long‐acting insulin glargine and the glucagon‐like peptide‐1 receptor agonist lixisenatide in patients who developed diabetes after pancreatectomy.Materials and MethodsJapanese patients who developed diabetes after pancreatectomy were eligible for this study. Participants were treated with combination therapy of glargine and lixisenatide for 12 weeks. Fasting and postprandial plasma glucose, C‐peptide immunoreactivity, glycated hemoglobin, bodyweight, visceral fat and subcutaneous fat were measured.ResultsAt 12 weeks after initiation of lixisenatide, glycated hemoglobin levels decreased from 8.46 ± 1.64% to 6.81 ± 1.15%. In addition, 1‐h postprandial plasma glucose and 2‐h postprandial plasma glucose levels significantly decreased from 222.9 ± 56.2 mg/dL to 125.1 ± 37.5 mg/dL (P < 0.001) and from 247.5 ± 56.8 mg/dL to 115.1 ± 29.0 mg/dL (P < 0.001), respectively. Neither hypoglycemia nor clinically relevant adverse events occurred during this study.ConclusionsThe present study shows that combination therapy with basal insulin and glucagon‐like peptide‐1 receptor agonists after partial pancreatectomy can be a useful therapeutic option for providing effective glycemic control with a reduced risk of hypoglycemia.

Insights from cardiovascular outcome trials with novel antidiabetes agents: what have we learned? An industry perspective.

Owing to the close association of cardiovascular (CV) disease with type 2 diabetes and the uncertainty surrounding the CV safety of antidiabetes agents, in 2008 the Food and Drug Administration issued guidance for the demonstration of CV safety for new antidiabetes drugs. Recently the results from CV outcomes trials of three dipeptidyl peptidase-4 (DPP-4) inhibitors and a glucagon-like peptide-1 receptor agonist have been reported. The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial, the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE) trial, and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) assessed the safety of saxagliptin, alogliptin, and sitagliptin, respectively, in patients with type 2 diabetes with CV disease or at high risk for CV disease. The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) assessed the safety of lixisenatide in patients with type 2 diabetes and a recent acute coronary syndrome event. The results show that these agents neither increased nor deceased major adverse CV events (CV death, nonfatal myocardial infarction, and nonfatal stroke) compared with placebo. However, the resources needed to conduct these studies may detract from the ability to understand the potential long-term benefit and risk in the majority of patients that are candidates for use of these medications.

Clinical experience with lixisenatide in patients with obesity and type 2 diabetes

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk.

Lixisenatide is Effective and Well Tolerated in Patients with Type 2 Diabetes Mellitus and Renal Impairment

This post-hoc assessment evaluated the efficacy and safety of the once-daily prandial glucagon-like peptide -1 (GLP-1) receptor agonist lixisenatide in patients with type 2 diabetes mellitus and renal impairment (RI).

Efficacy and safety of lixisenatide in Japanese patients with type2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal-S.

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 MethodsIn 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.ConclusionsIn 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.

Lixisenatide Significantly Increases the Probability of a A1C Response in Patients Not Adequately Controlled on Oral Antihyperglycemic Agents

To evaluate the response to lixisenatide, a novel once-daily glucagon-like peptide-1 receptor agonist, as add on to 1 oral antihyperglycemic agent (OAA) and 2 OAAs in patients with type 2 diabetes mellitus (T2DM) and the patient characteristics that may predict a response. Data were extracted from 5 randomized, 24-week, double-blind, placebo-controlled trials of the efficacy and safety of lixisenatide in patients with T2DM with inadequate glycemic control: GetGoal-M, -F1, -S, -P and -M Asia. Response was defined as the proportion of patients achieving A1C <7% or an A1C reduction of ≥1%. Evaluated predictors of response were age, gender, race, diabetes duration and baseline A1C. Significantly more patients achieved A1C <7% with lixisenatide + 1 OAA vs. placebo (43.0 vs. 23.0%, respectively; p<0.0001) and with lixisenatide + 2 OAAs vs. placebo (42.1 vs. 18.0%, respectively; p<0.0001). Significantly more patients achieved a response with lixisenatide + 1 OAA vs. placebo (59.8 vs. 35.4%, respectively; p<0.0001) and lixisenatide + 2 OAAs vs. placebo (60.2% vs. 27.5%, respectively; p<0.0001). No baseline characteristics were a strong predictor of response. In multivariable regression analysis, lixisenatide + 1 OAA and lixisenatide + 2 OAAs was 4.17 times (95% CI: 3.21, 5.41) and 2.81 times (95% CI: 2.14, 3.70) more likely to produce a A1C response vs. placebo, respectively. Lixisenatide added to 1 OAA or 2 OAAs significantly improved A1C and led to a higher proportion of patients reaching A1C <7% or an A1C reduction of ≥1% vs. placebo.

Consistent Reduction of Postprandial Glucagon and Insulin by Lixisenatide in the GetGoal Clinical Trial Program

To evaluate 2-hour glucose, glucagon and insulin changes following a standardized mixed-meal tolerance test before and after 24 weeks of treatment with the once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide* in patients with type 2 diabetes mellitus (T2DM). This was a meta-analysis of data from 6 randomized, placebo-controlled studies within the lixisenatide phase III GetGoal program. Studies included: lixisenatide in patients insufficiently controlled on diet and exercise (GetGoal-Mono), lixisenatide in combination with oral antihyperglycemic agents (GetGoal-M and GetGoal-S) and lixisenatide in combination with basal insulin ± oral antihyperglycemic agents (GetGoal-Duo 1, GetGoal-L and GetGoal-L-Asia). Meta-analysis was performed (lixisenatide n=1124 vs. placebo n=707) combining ANCOVA least squares (LS) mean values using an inverse variance weighted analysis. Lixisenatide significantly reduced 2-hour postprandial glucose from baseline (LS mean difference vs. placebo: –4.9 mmol/L, p<0.0001, Figure) and glucose excursions (LS mean difference vs. placebo: –4.5 mmol/L, p<0.0001). As measured in 2 studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: –19.0 ng/L, p<0.0001) and insulin (LS mean difference vs. placebo: –64.8 pmol/L, p<0.0001), although the glucagon/insulin ratio was increased (LS mean difference vs. placebo: 0.15, p=0.02) vs. placebo. In subjects with T2DM, lixisenatide potently reduces the glucose excursion after meal ingestion in association with marked reductions in glucagon and insulin levels. It is suggested that diminished glucagon secretion and slower gastric emptying contribute to reduced hepatic glucose production and delayed glucose absorption, enabling postprandial glycemia to be controlled with less demand on beta-cell insulin secretion.