Advancing Therapy in Suboptimally Controlled Basal Insulin-Treated Type 2 Diabetes: Clinical Outcomes With iGlarLixi Versus Premix BIAsp 30 in the SoliMix Randomized Controlled Trial.

OBJECTIVE: To directly compare the efficacy and safety of a fixed-ratio combination, of insulin glargine 100 units/mL and the glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi), with those of a premix insulin analog, biphasic aspart insulin 30 (30% insulin aspart and 70% insulin aspart protamine) (BIAsp 30) as treatment advancement in type 2 diabetes suboptimally controlled on basal insulin plus oral antihyperglycemic drugs (OADs). RESEARCH DESIGN AND METHODS: In SoliMix, a 26-week, open-label, multicenter study, adults with suboptimally controlled basal insulin-treated type 2 diabetes (HbA1c ≥7.5% and ≤10%) were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy end points were noninferiority in HbA1c reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30. RESULTS: Both primary efficacy end points were met: after 26 weeks, baseline HbA1c (8.6%) was reduced by 1.3% with iGlarLixi and 1.1% with BIAsp 30, meeting noninferiority (least squares [LS] mean difference -0.2% [97.5% CI -0.4, -0.1]; P < 0.001). iGlarLixi was also superior to BIAsp 30 for body weight change (LS mean difference -1.9 kg [95% CI -2.3, -1.4]) and percentage of participants achieving HbA1c <7% without weight gain and HbA1c <7% without weight gain and without hypoglycemia (all P < 0.001). iGlarLixi was also superior versus BIAsp 30 for HbA1c reduction (P < 0.001). Incidence and rates of American Diabetes Association level 1 and 2 hypoglycemia were lower with iGlarLixi versus BIAsp 30. CONCLUSIONS: Once-daily iGlarLixi provided better glycemic control with weight benefit and less hypoglycemia than twice-daily premix BIAsp 30. iGlarLixi is a more efficacious, simpler, and well-tolerated alternative to premix BIAsp 30 in suboptimally controlled type 2 diabetes requiring treatment beyond basal insulin plus OAD therapy. VIDEO 1: diacare;dc21-0393v4/F1F1f1Infographic available at https://care.diabetesjournals.org/content/dc21-0393-infographic.

Advancing therapy with iGlarLixi versus premix BIAsp 30 in basal insulin-treated type 2 diabetes: Design and baseline characteristics of the SoliMix randomized controlled trial.

AIM: Premix insulin is commonly used in some regions of the world, despite the higher risk of hypoglycaemia and weight gain compared with basal insulin, based on the premise that it offers a simplified insulin regimen. iGlarLixi is a once-daily titratable fixed-ratio formulation that combines basal insulin glargine 100 units/mL (iGlar) and the GLP-1 RA, lixisenatide, which offers a single-injection option for treatment intensification, with improved HbA1c reductions, similar hypoglycaemia risk and more favourable bodyweight profiles over iGlar alone. This randomized controlled study directly compares, for the first time, treatment intensification with iGlarLixi versus premix insulin analogue biphasic insulin aspart 30 (BIAsp 30) in adults with T2D inadequately controlled on basal insulin in combination with one or two oral antihyperglycaemic drugs. MATERIALS AND METHODS: This was an open-label, active-controlled, comparative, parallel-group, multicentre, phase 3b study. In total, 887 adults with T2D uncontrolled on basal insulin were randomized to switch to either iGlarLixi once daily, or BIAsp 30 twice daily, for 26 weeks. RESULTS: Overall, 887 participants were enrolled (mean age 59.8 years, 50.2% female) from 89 centres in 17 countries. At baseline, 65.6% had a duration of T2D of 10 years or longer, and the mean HbA1c at baseline was 8.6%. CONCLUSIONS: The study directly compared the efficacy and safety of iGlarLixi versus BIAsp 30 in people with T2D uncontrolled on basal insulin and one or more oral antihyperglycaemic agents. These results provide robust clinical data that may inform clinicians in their therapeutic management of people with T2D uncontrolled on basal insulin requiring additional therapy.

Equal improvement in glycaemia with lixisenatide given before breakfast or the main meal of the day.

AIMS: The aim of this study is to explore whether administration timing affects glycaemic control by lixisenatide once-daily in type 2 diabetes mellitus (T2DM). METHODS: A phase IIIb, open-label, 1:1 randomized, active-controlled, 24-week multicentre study of T2DM patients inadequately controlled on metformin was conducted. Patients were administered lixisenatide before breakfast or the main meal. The primary endpoint was change from baseline at week 24 in glycated haemoglobin (HbA1c). Other endpoints: changes in body weight, fasting plasma glucose (FPG), 7-point self-monitored plasma glucose (SMPG) and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) score. Adverse events (AEs) were monitored. RESULTS: Mean change in HbA1c from baseline at week 24 was -0.65% (-7.1mmol/mol; main meal) and -0.74% (-8.1mmol/mol; breakfast). Mean changes in FPG, body weight and DTSQs score were comparable between groups. The mean change in body weight (kg) was -2.60 (main meal) and -2.80 (breakfast group). The 7-point SMPG profiles showed greatest reductions in postprandial glucose after the meal at which lixisenatide was administered, with a residual effect seen on the subsequent meal. AE rates were similar between groups, including gastrointestinal AEs. CONCLUSIONS: Lixisenatide before the main meal was noninferior to lixisenatide before breakfast in patients insufficiently controlled on metformin. Lixisenatide treatment allows flexibility in administration timing.

First evaluation using a validated scale of the risk of congestive heart failure among hypertensive patients treated by general practitioners (O-PREDICT survey).

BACKGROUND: Routine management of hypertensive adults is based on assessment of risk factors for coronary artery disease; risk factors for heart failure (HF) remain poorly investigated despite the key role of hypertension in HF development. AIM: To assess the components of HF risk in hypertensive adults in primary care, compare physicians' estimations of HF and global cardiovascular risks with established calculation algorithms, and assess the concordance of these algorithms. METHODS: O-PREDICT was a transverse, observational, multicentre French survey conducted in 2006 among general practitioners who included the first hypertensive, non-HF patient seen in each of three age classes (<60, 60-70, >70 years). Estimations of HF and global cardiovascular risks (at 4 and 10 years, respectively) were performed subjectively during the consultation and calculated a posteriori according to algorithms from the Framingham cohort and the European SCORE database, respectively. For each of these methods, patients were stratified into four risk categories (i.e., no, low, moderate, high). RESULTS: One thousand five hundred and thirty seven physicians recruited 4523 patients (61% men; 64.5+/-10.9 years; systolic blood pressure 149.9+/-15.4 mmHg); most (67.2%) patients had one or two cardiovascular/HF risk factors (dyslipidaemia 48.8%, left ventricular hypertrophy 25.3%, diabetes 18.8%, coronary artery disease 8.8%, valvulopathy 6.1%); the number increased with advancing age and in men versus women. According to the Framingham algorithm, the risk of HF (mean 5.4+/-8.5%; 13.4% of patients at high risk) increased with advancing age (p<0.001), nearly doubling for each decade increase. According to the European SCORE system, global cardiovascular risk (mean 5.4+/-4.3%) was moderate or elevated in 48.1% of patients. Concordance between physicians' estimations and theoretical calculations for HF and global risks was poor, as was concordance between algorithms (kappa(w)=0.28, 0.12, 0.11, respectively). CONCLUSION: More than one in 10 hypertensive patients seen in primary care is at high risk of HF at 4 years according to the Framingham model; this algorithm appears to offer additional information to that provided by the SCORE system. Physicians' estimations of risks correlated poorly with algorithm calculations, suggesting that the use of these tools in general practice should be encouraged.

Comparison of the efficacy of rosuvastatin versus atorvastatin in reducing apolipoprotein B/apolipoprotein A-1 ratio in patients with acute coronary syndrome: results of the CENTAURUS study.

BACKGROUND: The mechanism underlying statin-induced event reduction in patients with acute coronary syndrome remains unclear. AIMS: To assess the efficacy of rosuvastatin 20mg versus atorvastatin 80 mg in reducing the apolipoprotein B/apolipoprotein A-1 (apoB/apoA-1) ratio at 3 months. Non-inferiority of rosuvastatin 20mg versus atorvastatin 80 mg in reducing low-density lipoprotein cholesterol at 1 and 3 months was also assessed. METHODS: Patients with non-ST-elevation acute coronary syndrome were enrolled into this randomized, double blind, parallel-group trial. RESULTS: In total, 753 patients (369, rosuvastatin 20mg; 384, atorvastatin 80 mg) were included in the intention-to-treat analysis; 478 patients (226, rosuvastatin 20mg; 252, atorvastatin 80 mg) were included in the per-protocol analysis. Rosuvastatin 20mg was more effective than atorvastatin 80 mg in decreasing apoB/apoA-1 ratio at 1 month (-44.4% vs -42.9%, p=0.02) but not at 3 months (both -44.4%, p=0.87). Low-density lipoprotein cholesterol decreased by approximately 50% after 1 and 3 months in both groups. Non-inferiority of rosuvastatin 20mg versus atorvastatin 80 mg was demonstrated at 1 month (difference, -0.3% [95% confidence interval, -2.7; +2.1]), but not at 3 months (+1.0% [-1.6; 3.5]) (intention-to-treat analysis). In the per-protocol analysis, non-inferiority of rosuvastatin 20mg was demonstrated at both 1 (-0.7% [-3.5; 2.0]) and 3 (-0.5% [-3.5; 2.5]) months. CONCLUSION: In patients with non-ST-elevation acute coronary syndrome, rosuvastatin 20mg decreased apoB/apoA-1 ratio at 1 month more than atorvastatin 80 mg. No difference could be shown at 3 months; thus, the primary endpoint was not met.

Improvement in the management of chronic heart failure since the publication of the updated guidelines of the European Society of Cardiology. The Impact-Reco Programme.

AIMS: Recent studies have shown that prescription rates and doses of recommended drugs for chronic heart failure (CHF) are not optimal in daily practice. The aim of the Impact-Reco programme was to analyse prescription rates of CHF drugs in stable outpatients with CHF related to left ventricular (LV) systolic dysfunction in two similar surveys in France. METHODS AND RESULTS: The two surveys, which included 1917 and 1974 patients, were performed between September 2004 to March 2005 and September 2005 to May 2006, respectively. Prescription rates of angiotensin-converting enzyme-inhibitors (ACE-I) remained stable (71 vs. 68%, respectively), whereas the proportion of patients receiving angiotensin receptor blockers (21 vs. 30%, P < 0.0001) and beta-blockers (65 vs. 70% P < 0.0001) increased significantly. Doses of ACE-I and beta-blockers increased significantly between the two surveys. However, the improvement was of lesser magnitude in some subgroups of patients, such as elderly patients or patients with renal failure. CONCLUSION: The Impact-Reco programme found an improvement in prescription rates and in the dosage of neurohumoral antagonists in French outpatients with stable CHF. However, there is still room for improvement, especially regarding the doses of medications and the treatment of some subgroups of patients such as the elderly and patients with renal failure.