Jay Lin

Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy

As glargine, an analog of human insulin, is increasingly used during pregnancy, a meta-analysis assessed its safety in this population. A systematic literature search identified studies of gestational or pregestational diabetes comparing use of insulin glargine with human NPH insulin, with at least 15 women in both arms. Data was extracted for maternal outcomes (weight at delivery, weight gain, 1st/3rd trimester HbA1c, severe hypoglycemia, gestation/new-onset hypertension, preeclampsia, and cesarean section) and neonatal outcomes (congenital malformations, gestational age at delivery, birth weight, macrosomia, LGA, 5 minute Apgar score >7, NICU admissions, respiratory distress syndrome, neonatal hypoglycemia, and hyperbilirubinemia). Relative risk ratios and weighted mean differences were determined using a random effect model. Eight studies of women using glargine (331) or NPH (371) were analyzed. No significant differences in the efficacy and safety-related outcomes were found between glargine and NPH use during pregnancy.

Once-daily prandial lixisenatide versus once-daily rapid-acting insulin in patients with type 2 diabetes mellitus insufficiently controlled with basal insulin: analysis of data from five randomized, controlled trials

AIMSnTo compare the efficacy and safety of lixisenatide (LIXI), a once-daily prandial glucagon-like peptide-1 (GLP-1) receptor agonist, as add-on to basal insulin (Basal+LIXI) versus once-daily rapid-acting insulin (Basal+RAI) in patients with type 2 diabetes mellitus (T2DM).nnnMETHODSnData were extracted from five randomized controlled trials assessing the efficacy and safety of basal insulin+insulin glulisine (n=3) or basal insulin+LIXI (n=2). Patients in the Basal+LIXI cohort were matched to patients in the Basal+RAI cohort using propensity score matching.nnnRESULTSnIn the matched population, Basal+LIXI was twice as likely to reach composite outcomes of glycated haemoglobin (HbA1c) <7% and no symptomatic hypoglycaemia compared with the Basal+RAI group (odds ratio [OR]: 1.90; 95% confidence interval [CI]: 1.01, 3.55; P=0.0455), as well as HbA1c <7% and no severe hypoglycaemia (OR: 1.97; 95 CI: 1.06, 3.66; P=0.0311). Furthermore, Basal+LIXI was more than twice as likely to reach HbA1c <7%, no weight gain and no symptomatic hypoglycaemia (OR: 2.58; 95% CI: 1.23, 5.40; P=0.0119).nnnCONCLUSIONSnBoth basal+LIXI and Basal+RAI improved glycaemic control in patients with T2DM with inadequate glycaemic control on basal insulin. Basal+LIXI offers an effective therapeutic option to advance basal insulin therapy, improving glucose control without weight gain and with less risk of hypoglycaemia than prandial insulin.

Lixisenatide Treatment for Older Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetics: Meta-Analysis of Five Randomized Controlled Trials

AimEvaluate the efficacy and safety of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in older patients with type 2 diabetes mellitus (T2DM) insufficiently controlled on oral antidiabetics (OADs).MethodsA meta-analysis was conducted on data from older patients (≥65xa0years) from five of the GetGoal trials, in which patients with T2DM were treated with lixisenatide 20xa0µg once daily or placebo, as an add-on to OADs. The primary endpoint in all trials was change from baseline at week 24 in glycated hemoglobin (HbA1c). Other endpoints included changes in post-prandial plasma glucose (PPG), fasting plasma glucose (FPG) and weight. Composite and safety endpoints were also analyzed.ResultsA total of 501 patients aged ≥65xa0years were included in this meta-analysis: 304 received lixisenatide plus OADs and 197 received placebo as add-on to OADs. Lixisenatide as an add-on to OADs significantly reduced HbA1c, PPG, FPG and weight, with placebo-corrected treatment effects at week 24 of −0.54% (pxa0<xa00.0001), −126xa0mg/dL (pxa0<xa00.0001), −13xa0mg/dL (pxa0=xa00.0005) and −0.90xa0kg (pxa0=xa00.0021), respectively. Patients receiving lixisenatide plus OADs were significantly more likely to achieve composite (HbA1c levels <7%, HbA1c levels <7% and no symptomatic hypoglycemia, and HbA1c levels <7%, no weight gain and no symptomatic hypoglycemia) and safety endpoints than those receiving placebo plus OADs. Symptomatic hypoglycemia was experienced by 8.55% and 3.55% of patients in the lixisenatide plus OADs and placebo plus OADs groups, respectively (pxa0=xa00.0276), although no serious hypoglycemic episodes were reported.ConclusionsLixisenatide plus OADs improved glycemic control in older patients inadequately controlled on OADs compared with placebo plus OADs. Lixisenatide is well tailored to the pathophysiology of T2DM in older patients.

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

AIMSnTo 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).nnnMATERIALS AND METHODSnIn 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.nnnRESULTSnPatients (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.nnnCONCLUSIONSnLixisenatide 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.

Predictors of outcomes in patients with type 2 diabetes in the lixisenatide GetGoal clinical trials

To explore the treatment outcomes in adult patients with type 2 diabetes (T2D) enrolled in the GetGoal trials of lixisenatide (LIXI), and the predictive effects of baseline characteristics on outcomes.

Lixisenatide reduces glycaemic variability in insulin-treated patients with type 2 diabetes

Chronic hyperglycaemia and glucose variability are associated with the development of chronic diabetes‐related complications. We conducted a pooled analysis of patient‐level data from three 24‐week, randomized, phase III clinical trials to evaluate the impact of lixisenatide (LIXI) on glycaemic variability (GV) vs placebo as add‐on to basal insulin. The main outcome GV measures were standard deviation (s.d.), mean amplitude of glycaemic excursions (MAGE), mean absolute glucose (MAG) level, area under the curve for fasting glucose (AUC‐F), and high (HBGI) and low blood glucose index (LBGI). The change in GV metrics over 24u2009weeks and relationships among baseline GV, patient characteristics and outcomes were assessed. Data were pooled from 1198 patients (665 LIXI, 533 placebo). Values for s.d., MAG level, MAGE, HBGI, and AUC‐F significantly decreased with LIXI vs placebo, while LBGI values were unchanged. Higher baseline GV measures correlated with older age, longer type 2 diabetes duration, lower body mass index, higher baseline glycated/haemogobin, greater reduction in postprandial glucose (PPG) level, and higher rates of symptomatic hypoglycaemia. These data show that LIXI added to basal insulin significantly reduced GV and PPG excursions vs placebo, without increasing the risk of hypoglycaemia (LBGI).

Predictors of type 2 diabetes patients’ outcomes in the lixisenatide GetGoal clinical trials

To explore the treatment outcomes in adult patients with type 2 diabetes (T2D) enrolled in the GetGoal trials of lixisenatide (LIXI), and the predictive effects of baseline characteristics on outcomes.

6.3 Efficacy and Safety of Lixisenatide in Elderly T2DM Patients: Subanalysis from the GetGoal Program (916-P)

SamenvattingThe number of elderly people with T2DM is increasing; therefore, efficacy and safety of antidiabetic drugs for vulnerable patients is a key question for individualized treatment.

Efficacy and Safety of Lixisenatide in Elderly Type 2 Diabetes Mellitus Patients: Subanalysis from the GetGoal Program

s / Can J Diabetes 37 (2013) S13eS84 S28 of previous exposure to insulin, patients with high A1c level showed lower contribution from PPG compared to patients with low A1c level. Conclusion: In patients with A1c˂8.5, PPG contribution to hyperglycemia is higher than in patients with A1c 8.5. In IT patients, PPG contribution accounts for approximately 50% of hyperglycemia. These findings suggest that depending on the A1c level and whether a T2DM patient is IN or IT, an individualized approach should be considered for initiating or intensifying treatment if they are above the A1c target of 7%.