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Aims This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. Methods and results The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as ≥6 months of AF/AFL until end of study) or permanent SR (defined as ≥6 months of SR until end of study) were calculated using Kaplan–Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56–0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09–1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). Conclusion These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling. Clinical trial registration NCT00174785

Diabetes therapy 13(1), 57-73 (2022). doi:10.1007/s13300-021-01179-8, Published by Springer Healthcare Communications, New York, NY [u.a.]

Using pooled data from the REALI European database, we evaluated the impact of previous basal insulin (BI) type on real-life effectiveness and safety of switching to insulin glargine 300 U/ml (Gla-300) in people with suboptimally controlled type 2 diabetes.Patient-level data were pooled from 11 prospective, open-label, 24-week studies. Participants were classified according to the type of prior BI. Of the 4463 participants, 1282 (28.7%) were pre-treated with neutral protamine Hagedorn (NPH) insulin and 2899 (65.0%) with BI analogues (BIAs), and 282 (6.3%) had undetermined prior BI.There were no meaningful differences in baseline characteristics between subgroups, except for a higher prevalence of diabetic neuropathy in the NPH subgroup (21.6% versus 7.8% with BIAs). Mean ± standard deviation haemoglobin A1c (HbA1c) decreased from 8.73 ± 1.15% and 8.35 ± 0.95% at baseline to 7.71 ± 1.09% and 7.82 ± 1.06% at week 24 in the NPH and BIA subgroups, respectively. Least squares (LS) mean change in HbA1c was - 0.85% (95% confidence interval - 0.94 to - 0.77) in NPH subgroup and - 0.70% (- 0.77 to - 0.64) in BIA subgroup, with a LS mean absolute difference between subgroups of 0.16 (0.06-0.26; p = 0.002). Gla-300 mean daily dose was slightly increased at week 24 by 0.07 U/kg/day (approximately 6 U/day) in both subgroups. Incidences of symptomatic and severe hypoglycaemia were low, without body weight change.Irrespective of previous BI therapy (NPH insulin or BIAs), switching to Gla-300 improved glycaemic control without weight gain and with low symptomatic and severe hypoglycaemia incidences. However, a slightly greater glucose-lowering effectiveness was observed in people pre-treated with NPH insulin.

The effectiveness of Gla-300 in PWT2D switching from NPH is not widely documented. REALI database combines individual data from 14 European studies in T2D. We analyzed data from PWT2D uncontrolled on prior basal insulin (BI) , 1282 switching from NPH and 2899 from other non-NPH BIs (mainly glargine 100 U/mL, 67%) to Gla-300. In the NPH group, mean±SD age was 63±9.4 years, BMI 32.5±5.8 kg/m2, and median diabetes duration 12 years. The majority previously used biguanides (71%) , followed by sulfonylureas (20%) , and dipeptidyl peptidase 4 inhibitors (18%) . HbA1c markedly improved after a 24-week Gla-300 therapy (Figure 1A) . Mean±SD fasting plasma glucose (FPG) decreased from 188.8±55.9 mg/dL at Baseline to 143.3±45.5 at Week 24. Gla-300 was started at a mean dose of 29.4 U/day and titrated up to 35.6 at Week 24, with no body weight (BW) change. In the non-NPH BI group, baseline characteristics were comparable to those in the NPH group, except for higher baseline HbA1c and FPG in the latter. Figure 1B illustrates HbA1c improvement in the non-NPH BI group, at a mean Gla-300 starting dose of 35.4 U/day increasing to 41.7 at Week 24, with no BW change. Hypoglycemia was similarly low in both groups. This analysis shows that PWT2D, previously uncontrolled on BI, benefited from switching to Gla-300 in terms of HbA1c improvement, and this was especially observed in those previously treated with NPH. Disclosure D.Müller-wieland: Advisory Panel; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. N.Freemantle: Consultant; Novo Nordisk, Research Support; Aimmune, ALK-Abelló A/S, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Sanofi, Vertex Pharmaceuticals Incorporated, Speaker's Bureau; Abbott. R.C.Bonadonna: Advisory Panel; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk. C.Mauquoi: None. G.Bigot: None. M.Bonnemaire: Employee; Sanofi. P.Gourdy: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mundipharma, Novo Nordisk, Sanofi, Sanofi, Speaker's Bureau; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk. D.Mauricio: Advisory Panel; Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Speaker's Bureau; Almirall, S.A., Esteve, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. Funding Sanofi

Pre-Breakfast iGlarLixi efficacy and safety were demonstrated in several randomized controlled trials. Whether time of administration could impact effectiveness in real life clinical practice is unknown. In the European REALI pooled database, we analyzed patient-level data of 1303 people with type 2 diabetes (T2D) treated with iGlarLixi for 24 weeks. Of these, 33% had the injection pre-Breakfast, 20% pre-Lunch, 31% pre-Dinner, while 16% switched time of injection. Overall, baseline characteristics were similar among groups with mean±SD age of 61±9.0 years, BMI 32.2±5.5 kg/m2, and median diabetes duration of 9 years. People with T2D previously used 1 oral glucose-lowering agent (57%) or ≥2 (43%) . A total of 590 people (45%) were insulin pretreated for a median duration of 2.5 years. Mean±SD HbA1c improved from 9.1±1.4% at Baseline to 7.7±1.2% at Week 24, with a least square mean decrease of 1.4% [95% CI: -1.50;-1.36], and most notable reduction in the pre-Breakfast group as shown in Figure 1. Mean±SD fasting plasma glucose decreased by 50.0±54.2 mg/dL and body weight by 1.8±6.6 kg at Week 24 with no difference between groups. Hypoglycemia reports were low in all groups.This analysis confirms the effectiveness of iGlarLixi at all administration times; pre-Breakfast may be preferable when there is a choice. Disclosure M.Haluzik: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Lilly Diabetes, Novartis AG. J.Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. C.Guja: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Servier Laboratories. M.Bonnemaire: Employee; Sanofi. G.Bigot: None. M.Tournay: None. J.T.Kis: Speaker's Bureau; 77 Elektronika Kft., AstraZeneca, Boehringer Ingelheim International GmbH, EGIS Pharmaceuticals, Lilly Diabetes, Novo Nordisk, Sanofi. N.Freemantle: Consultant; Novo Nordisk, Research Support; Aimmune, ALK-Abelló A/S, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Sanofi, Vertex Pharmaceuticals Incorporated, Speaker's Bureau; Abbott. Funding Sanofi

Diabetes therapy 12(4), 1073-1097 (2021). doi:10.1007/s13300-021-01030-0, Published by Springer Healthcare Communications, New York, NY [u.a.]

Aims To obtain safety and efficacy data of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting in high cardiovascular (CV) risk patients with heterozygous familial hypercholesterolaemia (HeFH) or very-high low-density lipoprotein cholesterol (LDL-C) levels despite maximally tolerated dose of statin ± other lipid-lowering therapies (MTD ± LLTs). ODYSSEY APPRISE was a prospective, single-arm, Phase 3b open-label (≥12 weeks to ≤ 30 months) European/Canadian study with alirocumab. Methods and results Patients received alirocumab 75 or 150 mg every 2 weeks, with dose adjustment based on physician’s judgment. In total, 994 patients were enrolled and treated. The mean [standard deviation (SD)] duration of alirocumab exposure was 72.4 (42.5) weeks. Patients with HeFH were younger [mean (SD) age of 53.8 (11.6) vs. 61.6 (10.1) years], more likely to be female (41.7% vs. 29.1%) and had higher baseline LDL-C compared with non-familial hypercholesterolaemia (non-FH) patients [mean (SD) of 5.1 (1.7) vs. 4.1 (1.1) mmol/L]. The overall incidence of treatment-emergent adverse events (TEAEs) was 71.6%; common TEAEs included nasopharyngitis (7.8%), myalgia (7.1%), and headache (6.2%). At Week 12, mean (SD) LDL-C was reduced by 54.8 (20.1)% from baseline [2.6 (1.2) mmol/L], maintained for the trial duration. LDL-C was reduced below 1.8 mmol/L and/or by ≥50% reduction from baseline in 69.1% of patients overall, and for 64.7 and 77.4% of the HeFH and non-FH subgroups, respectively. Conclusion In a real-life setting in patients with hypercholesterolaemia and high CV risk, alirocumab was generally well tolerated and resulted in clinically significant LDL-C reductions.

Publisher Copyright: © 2022 Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m2. “Severe insulin-resistant diabetes” was found least often (4.6 %) and prevalence of “mild age-related diabetes” (23.9 %) was mainly influenced by age at onset of diabetes and age cut-offs. Subgroup characteristics were widely comparable to those from real-world cohorts, but all subgroups showed higher frequencies of diabetes-related complications which were associated with longer diabetes duration. A high proportion of “severe insulin-deficient diabetes” (25.4 %) was identified with poor pre-study glycaemic control. Conclusions: Classification of RCT participants into newly-defined diabetes subgroups revealed the existence of a heterogeneous population of T2DM. For future RCTs, subgroup-based randomisation of T2DM will better define the target population and relevance of the outcomes by avoiding clinical heterogeneity.

Diabetes therapy 12(4), 1159-1174 (2021). doi:10.1007/s13300-021-01031-z, Published by Springer Healthcare Communications, New York, NY [u.a.]

IntroductionType 2 diabetes mellitus (T2DM) is a common and heterogeneous disease. Using advanced analytic approaches to explore real-world data may identify different disease characteristics, responses to treatment and progression patterns. Insulin glargine 300 units/mL (Gla-300) is a second-generation basal insulin analogue with preserved glucose-lowering efficacy but reduced risk of hypoglycaemia. The purpose of the REALI pooled analysis described in this paper is to advance the understanding of the effectiveness and real-world safety of Gla-300 based on a large European patient database of postmarketing interventional and observational studies.Methods and analysisIn the current round of pooling, REALI will include data from up to 10 000 subjects with diabetes mellitus (mostly T2DM) from 20 European countries. Outcomes of interest include change from baseline to week 24 in haemoglobin A1c, fasting plasma glucose, self-measured plasma glucose, body weight, insulin dose, incidence and rate of any-time-of-the-day and nocturnal hypoglycaemia. The data pool is being investigated using two complementary methodologies: a conventional descriptive, univariate and multivariable prognostic analysis; and a data-mining approach using subgroup discovery to identify phenotypic clusters of patients who are highly associated with the outcome of interest. By mid-2019, deidentified data of 7584 patients were included in the REALI database, with a further expected increase in patient number in 2020 as a result of pooling additional studies.Ethics and disseminationThe proposed study does not involve collection of primary data. Moreover, all individual study protocols were approved by independent local ethics committees, and all study participants provided written informed consent. Furthermore, patient data is deidentified before inclusion in the REALI database. Hence, there is no requirement for ethical approval. Results will be disseminated via peer-reviewed publications and presentations at international congresses as data are analysed.

Despite an increasing number of patients with type 2 diabetes (T2D) in the older population, clinical evidence for different therapeutic strategies in the elderly is poor. Therefore, we used the REALI pooled database, which includes a large number of studies conducted in different European countries to evaluate the impact of initiating insulin glargine 300 U/mL (Gla-300) in older patients with T2D. Pooled efficacy and safety analyses of data from three interventional and five observational studies (pooled treated patients, n=5806) were performed on three age groups of patients: Disclosure R.C. Bonadonna: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis. D. Mauricio: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Speaker's Bureau; Self; Almirall, S.A., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Urgo Medical. D. Müller-Wieland: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Sanofi. G. Bigot: None. C. Mauquoi: None. A. Ciocca: Employee; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. P. Gourdy: Advisory Panel; Self; AstraZeneca. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. Speaker's Bureau; Self; Abbott, Amgen Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. Funding Sanofi

REALI pooled database, encompassing Gla-300 studies conducted in different European countries, is a platform to identify factors contributing to glycemic control in patients with uncontrolled T2D initiated on Gla-300. A stepwise multivariable regression analysis was performed on selected demographic and baseline characteristics associated with achieving HbA1c target Disclosure N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Sanofi. G. Bigot: None. M. Bonnemaire: Employee; Self; Sanofi. D. Mauricio: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Speaker's Bureau; Self; Almirall, S.A., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Urgo Medical. R.C. Bonadonna: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis. P. Gourdy: Advisory Panel; Self; AstraZeneca. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. Speaker's Bureau; Self; Abbott, Amgen Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. A. Ciocca: Employee; Self; Sanofi. D. Müller-Wieland: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Funding Sanofi

REALI pooled database, encompassing Gla-300 studies conducted in different European countries, is a platform to identify factors contributing to glycemic control in patients with uncontrolled T2DM initiated on Gla-300. A stepwise multivariable regression analysis was performed on selected demographic and baseline characteristics associated with HbA1c drop ≥ 0.5% after 6 months of Gla-300 treatment from 8 studies (3 interventional and 5 observational). The criterion for retention in the model was p ≤ 0.05. From the 2624 subjects included, 64.2% have dropped their HbA1c level by at least 0.5%, 56% were male and 37% were insulin naïve. Means ± SD were 64 ± 9.4 years for age and 32.2 ± 5.4 kg/m2 for BMI. Mean ± SD baseline HbA1c was 8.5 ± 1% and 0.29 ± 0.18 U/kg/day for Gla-300 starting dose. Multivariable analyses identified baseline HbA1c as the major predictive factor associated with HbA1c reduction, with a nonlinear relationship, and odds were higher in the highest baseline HbA1c value (p < 0.0001). Lower BMI (p = 0.048), shorter duration of diabetes (p = 0.016), being insulin naïve (p < 0.0001), and lower Gla-300 starting dose (p < 0.001) have also been identified as potential predictors of HbA1c improvement. These results can help clinicians to identify T2DM patients who are likely to benefit most from Gla-300 treatment. Disclosure G. Bigot: None. M. Bonnemaire: Employee; Self; Sanofi. R.C. Bonadonna: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis. P. Gourdy: Advisory Panel; Self; AstraZeneca. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. Speaker's Bureau; Self; Abbott, Amgen Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. D. Müller-Wieland: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. D. Mauricio: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Speaker's Bureau; Self; Almirall, S.A., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Urgo Medical. A. Ciocca: Employee; Self; Sanofi. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Sanofi. Funding Sanofi

Chronic kidney disease is common in patients with type 2 diabetes (T2D) and has an impact on the choice and dosage of T2D therapies, as well as on the individual’s glycemic target and the risk of hypoglycemia. We evaluated the impact of initiating insulin glargine 300 U/mL (Gla-300) in patients with T2D according to eGFR level, using the REALI pooled database which includes several Gla-300 studies conducted in different European countries. Pooled efficacy and safety analysis of data from three interventional studies was performed on patients treated with Gla-300 having an eGFR at baseline either ≥60 (n=923) or Disclosure D. Mauricio: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Speaker's Bureau; Self; Almirall, S.A., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Urgo Medical. P. Gourdy: Advisory Panel; Self; AstraZeneca. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. Speaker's Bureau; Self; Abbott, Amgen Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. R.C. Bonadonna: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Sanofi. G. Bigot: None. C. Mauquoi: None. A. Ciocca: Employee; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. D. Müller-Wieland: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Funding Sanofi

Inadequate control of cardiovascular (CV) risk is common in patients with heterozygous familial hypercholesterolemia (HeFH), or in non-FH patients at high CV risk, with low-density lipoprotein cholesterol (LDL-C) not at target despite maximally tolerated dose (MTD) statin ± other lipid lowering

TAKE CONTROL, a 24-week, multicenter, randomized, open-label, parallel-group study, evaluated self- vs. physician-led titration of Gla-300 in people with T2DM. Efficacy and safety outcomes in people 0.05). Adverse events were similar in each group. Self-titration of Gla-300 resulted in similar glycemic target achievement to physician-led titration, without an increased risk of hypoglycemia, irrespective of age. There was a trend for more people to reach fasting SMPG targets without hypoglycemia with self- vs. physician-led titration, including those ≥65 years. Disclosure K. Strojek: Research Support; Self; AstraZeneca. Other Relationship; Self; Sanofi-Aventis, Novo Nordisk A/S. Speaker's Bureau; Self; Servier, Eli Lilly and Company, MSD K.K., Boehringer Ingelheim GmbH. Research Support; Self; Pfizer Inc., Amgen Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc. G. Bigot: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. E. Delgado: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Sanofi-Aventis. Speaker's Bureau; Self; Esteve, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Lilly. Research Support; Self; Menarini Group. V. Donicova: None. M. Kvapil: None. N. Papanas: None. L. Popescu: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. R. Ritzel: Speaker's Bureau; Self; AstraZeneca. Consultant; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Consultant; Self; Servier. Speaker's Bureau; Self; Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp., Boehringer Ingelheim GmbH, Eli Lilly and Company, Novartis Pharmaceuticals Corporation. B. Schultes: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, AstraZeneca, Eli Lilly and Company, Bayer AG, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Sanofi, Eli Lilly and Company, MSD K.K., Bayer AG, Boehringer Ingelheim GmbH. L. Duvnjak: None.

Objective: To assess efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus (vs) insulin glargine 100 U/mL (Gla-100) in North American and non-North American people with type 2 diabetes mellitus on different background therapies.Methods: A patient-level meta-analysis of three international studies (EDITION 1, 2 and 3) was performed to examine glycemic control and hypoglycemia over 6 months in 2496 participants including 1420 participants in a North American sub-population (Gla-300, N=700; Gla-100, N=720). Endpoints included change in glycated hemoglobin (HbA1c), percentage of patients at target HbA1c at Month 6, incidence and rate of hypoglycemic events, change in body weight and insulin dose, as well as incidence of adverse events.Results: Mean change in HbA1c was comparable for Gla-300 and Gla100 in both regions (P=0.8347 for treatmentby- subgroup interaction). There were no regional differences in the percentage of participants achieving target HbA1c 0.1). North American participants treated with Gla-300 gained less weight than North American participants treated with Gla-100 (least squares mean change 0.64 kg vs 1.15 kg), whereas in non-North American participants the change in weight tended to be similar in both treatment groups (0.36 kg vs 0.32 kg). Treatment with Gla-300 and Gla-100 was well tolerated in both regions.Conclusion: Gla-300 provided comparable glycemic control to Gla-100 with consistently less hypoglycemia at any time of day and during the night, regardless of the region (North America/outside North America).