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Aims: To evaluate treatment advancement with insulin glargine 300 U/mL (Gla-300), with or without prior glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in type 2 diabetes (T2D)., Methods: Efficacy and safety outcomes of insulin-naïve patients intensifying with Gla-300, with/without prior GLP-1 RA therapy, were evaluated in three analyses (N = 3562): a pooled analysis of seven interventional studies, a subanalysis comparing participants who stopped GLP-1 RA therapy and initiated Gla-300 with those who received add-on Gla-300, and an expanded analysis including two observational studies., Results: Glycaemic outcomes, including HbA1c improvement and fasting plasma glucose, were similar between groups with/without prior GLP-1 RA use. HbA1c least squares mean change from baseline was - 1.7 % and - 1.6 % with and without prior GLP-1 RA, respectively. Glycaemic outcomes were similar between participants who stopped GLP-1 RA therapy when initiating Gla-300 and those who received add-on Gla-300, although more participants receiving add-on Gla-300 achieved HbA1c targets. The expanded analysis yielded similar results. Incidence of hypoglycaemia was low with no clinically relevant weight changes in all analyses., Conclusions: Treatment advancement with Gla-300 in patients with T2D, with/without prior GLP-1 RA therapy, improved glycaemic outcomes with no relevant impact on weight, while maintaining a low hypoglycaemia risk., Competing Interests: Declaration of competing interest All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, had full access to all the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. All authors participated in the interpretation of the data, the writing, reviewing, and editing of the manuscript, and had final responsibility for approving the published version. A. Cheng: Advisory board member for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Eisai, Eli Lilly, Insulet, HLS Therapeutics, Janssen, Novo Nordisk, Sanofi and Takeda. Speaking honoraria for Abbott Diabetes Care, Amgen, AstraZeneca, Bausch, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, GSK, Insulet, HLS Therapeutics, Janssen, Medtronic, Novo Nordisk, Pfizer and Sanofi. Consulting fees from Abbott Diabetes Care, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, Eisai, Insulet, HLS Therapeutics, Janssen, Novo Nordisk, Sanofi and Takeda. D. Mauricio: Advisory and/or speaking fees from AB-Biotics, Almirall, Esteve, Ferrer, Janssen, Lilly, Menarini, MSD, Novo Nordisk and Sanofi. Research grants to the institution from MSD, Novo Nordisk and Sanofi. R. Ritzel: Consultant for Sanofi, Novo Nordisk, Merck (MSD) and Eli Lilly, and has served on Speaker’s bureau for Sanofi, Novo Nordisk, Novartis, Eli Lilly, Merck (MSD), Bristol-Myers Squibb and AstraZeneca. M. E. Al-Sofiani: Has served on an advisory panel for Abbott, Medtronic, Insulet, VitalAire, and Sanofi. Honoraria for speaking/consultancy from Abbott, Eli Lilly, Medtronic, Novo Nordisk, Sanofi and VitalAire. T. Bailey: Research support from Abbott Diabetes, Abbott Rapid Diagnostics, Biolinq, Capillary Biomedical, Dexcom, Eli Lilly, Kowa, Livongo, Mannkind, Medtronic, Novo Nordisk, REMD, Sanofi, Sanvita, Senseonics, Viacyte, vTv Therapeutics and Zealand Pharma. Consulting honoraria from Abbott, CeQur, Lifescan, Mannkind, Medtronic, Novo Nordisk, Sanofi, Abbott Rapid Diagnostics, HagarTech, Intuity Medical, Perspirion, SequelMedTech and Ypsomed. Speaking honoraria from BD, Medtronic and Sanofi. Expert testimony consulting fees from Medtronic Diabetes. Travel/meeting support from Sanofi. M. A.Mabunay & M. Bonnemaire: Employees of Sanofi, may hold stocks/shares in Sanofi. L. Melas-Melt: Employee of Ividata Life Sciences, contracted to provide services to Sanofi. S.Mimouni: Advisory board member and speaker for Eli Lilly, Novo Nordisk and Sanofi. M. Davies: Has acted as a consultant, advisory board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi; an advisory board member for Lexicon, Pfizer, AstraZeneca, Zealand Pharma and Medtronic; and as a speaker for AstraZeneca. Grants received from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Janssen, Sanofi-Aventis, Eli Lilly and NIHR Leicester Biomedical Research Centre (which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University and the University of Leicester)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The aim of this work was to assess the safety and effectiveness of concomitant iGlarLixi and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) use in adults with type 2 diabetes (T2D) who fasted during Ramadan., Methods: Of the 420 eligible participants from the SoliRam study, 174 were using SGLT-2i in addition to iGlarLixi and 246 were not using SGLT-2i, referred to as SGLT-2i user and non-user, respectively. The primary endpoint was the proportion of participants experiencing ≥ 1 severe and/or symptomatic documented (< 70 mg/dl [< 3.9 mmol/l]) hypoglycemia., Results: More than 50% of participants in both groups were male. The mean weight, glycated hemoglobin (HbA1c), and fasting plasma glucose (FPG) were similar in both groups. Approximately half of participants in the SGLT-2i-user group and ~ 25% participants in the SGLT-2i-non-user group were on two oral anti-hyperglycemic drugs (OADs), whereas ~ 20% in the SGLT-2i-user group and ~ 1% of participants in the SGLT-2i-non-user group were on three OADs in addition to iGlarLixi. Around 35% and 55% of participants in the SGLT-2i-user and SGLT-2i-non-user groups, respectively, were taking concurrent sulphonylureas. About 97% of participants in both groups were able to fast for ≥ 25 days. The incidence of primary endpoint was low in both groups; SGLT-2i user: 0.6%, 4.2%, and 0.6% and SGLT-2i-non-user: 1.3%, 0.9% and 0% during pre-Ramadan, Ramadan, and post-Ramadan period, respectively. The incidence of severe and/or symptomatic documented (< 54 mg/dl [< 3.0 mmol/l]) hypoglycemia events was also low throughout the study, including during Ramadan. No severe hypoglycemia occurred during Ramadan in either group. Improvements in HbA1c and FPG, with a small reduction in weight, were observed from pre- to post-Ramadan in both groups. No serious adverse event was reported in either group., Conclusions: Concomitant iGlarLixi and SGLT-2i therapy with or without other OADs was demonstrated to be safe in adults with T2D during Ramadan fast, with a low risk of hypoglycemia and improvements in glycemic outcomes., (© 2024. The Author(s).)

Aim: To evaluate the efficacy of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) using derived time-in-range (dTIR)., Methods: Participant-level data from LixiLan-L, LixiLan-O and LixiLan-G were pooled and dTIR (70-180 mg/dL), derived time-above-range (> 180 mg/dL) and derived time-below-range (dTBR; < 70 mg/dL) were calculated from participant seven-point self-monitored blood glucose profiles., Results: This pooled analysis included data from 2420 participants receiving iGlarLixi (n = 1093), iGlar (n = 836), Lixi (n = 234) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA) (n = 257). Numerically greater improvements in least square (LS) means dTIR were seen from baseline to end of treatment (EOT) with iGlarLixi (25.7%) versus iGlar (15.8%), Lixi (11.7%) or GLP-1 RA (16.2%). At EOT, the mean (standard deviation) dTBR was 0.71% ± 3.4%, 0.61% ± 3.2%, 0.08% ± 1.0% and 0.0% ± 0.0% for iGlarLixi, iGlar, Lixi and GLP-1 RA, respectively. In a subgroup analysis, participants aged younger than 65 years (n = 1690) and 65 years or older (n = 713) showed numerically greater improvements in LS means dTIR from baseline to EOT with iGlarLixi versus iGlar, Lixi or GLP-1 RA., Conclusions: iGlarLixi achieved improvements in dTIR, with low dTBR values, providing further evidence to inform clinical outcomes with the use of iGlarLixi., (© 2024 Sanofi and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims/introduction: We analyzed patient-reported outcomes of people with type 2 diabetes to better understand perceptions and experiences contributing to treatment adherence., Materials and Methods: In the ongoing International Diabetes Management Practices Study, we collected patient-reported outcomes data from structured questionnaires (chronic treatment acceptance questionnaire and Diabetes Self-Management Questionnaire) and free-text answers to open-ended questions to assess perceptions of treatment value and side-effects, as well as barriers to, and enablers for, adherence and self-management. Free-text answers were analyzed by natural language processing., Results: In 2018-2020, we recruited 2,475 patients with type 2 diabetes (43.3% insulin-treated, glycated hemoglobin (HbA 1c ) 8.0 ± 1.8%; 30.9% with HbA 1c  <7%) from 13 countries across Africa, the Middle East, Europe, Latin America and Asia. Mean ± standard deviation scores of chronic treatment acceptance questionnaire (acceptance of medication, rated out of 100) and Diabetes Self-Management Questionnaire (self-management, rated out of 10) were 87.8 ± 24.5 and 3.3 ± 0.9, respectively. Based on free-text analysis and coded responses, one in three patients reported treatment non-adherence. Overall, although most patients accepted treatment values and side-effects, self-management was suboptimal. Treatment duration, regimen complexity and disruption of daily routines were major barriers to adherence, whereas habit formation was a key enabler. Treatment-adherent patients were older (60 ± 11.6 vs 55 ± 11.7 years, P < 0.001), and more likely to have longer disease duration (12 ± 8.6 vs 10 ± 7.7 years, P < 0.001), exposure to diabetes education (73.1% vs 67.8%, P < 0.05), lower HbA 1c (7.9 ± 1.8% vs 8.3 ± 1.9%, P < 0.001) and attainment of HbA 1c  <7% (29.7% vs 23.3%, P < 0.01)., Conclusions: Patient perceptions/experiences influence treatment adherence and self-management. Patient-centered education and support programs that consider patient-reported outcomes aimed at promoting empowerment and developing new routines might improve glycemic control., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aim: To assess the efficacy and safety of iGlarLixi in older people (≥65 years) with type 2 diabetes (T2D) advancing or switching from oral agents, a glucagon-like peptide-1 receptor agonist (GLP-1RA), or basal insulin., Materials and Methods: The data of participants aged <65 years and ≥65 years from four LixiLan trials (LixiLan-O, LixiLan-G, LixiLan-L, SoliMix) were evaluated over 26 or 30 weeks., Results: Participants aged <65/≥65 years (n = 1039/n = 497) had a mean baseline body mass index of 31.4 and 30.7 kg/m 2 and glycated haemoglobin (HbA1c) concentration of 66 mmol/mol (8.2%) and 65 mmol/mol (8.1%), respectively. Least squares mean HbA1c change from baseline to end of treatment (EOT) was -14.32 mmol/mol (-1.31%) (95% confidence interval [CI] -14.97, -13.77 [-1.37%, -1.26%]) for those aged <65 years and -13.66 mmol/mol (-1.25%) (95% CI -14.54, -12.79 [-1.33%, -1.17%]) for those aged ≥65 years. At EOT, achievement of HbA1c targets was similar between the group aged <65 years and the group aged ≥65 years: <53 mmol/mol (<7%) (59.0% and 56.5%, respectively), <59 mmol/mol (<7.5%) (75.5% and 73.0%, respectively) and <64 mmol/mol (<8%) (83.8% and 84.1%, respectively). The incidence and event rate of American Diabetes Association Level 1 hypoglycaemia during the studies were also comparable between the two groups: 26.7% and 28.2% and 1.7 and 2.1 events per patient-year for the group aged <65 years and the group aged ≥65 years, respectively. A clinically relevant reduction in HbA1c (>1% from baseline for HbA1c ≥64 mmol/mol [≥8%] or ≥0.5% from baseline for HbA1c <64 mmol/mol [<8%]) without hypoglycaemia was attained by 50.0% and 47.6% of participants aged <65 years and ≥65 years, respectively. Adverse events were similar between the two age groups., Conclusions: iGlarLixi is a simple, well-tolerated, once-daily alternative for treatment advancement in older people with T2D that provides significant improvements in glycaemic control without increasing hypoglycaemia risk, thus reducing the treatment burden., (© 2023 Sanofi and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: Sodium glucose co-transporter 2 inhibitors (SGLT2is) and/or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with proven cardio- and reno-protective benefits are recommended in people with type 2 diabetes (T2D) at high risk of cardiovascular disease, chronic kidney disease, and/or heart failure. This pooled analysis compared efficacy and safety outcomes of iGlarLixi with or without SGLT2is in people with T2D., Methods: This post hoc analysis evaluated outcomes in participants who were receiving an SGLT2i when initiating iGlarLixi (SGLT2i users) and those who were not (SGLT2i non-users) in a pooled dataset from three trials: LixiLan-G (advancing from a GLP-1 RA), SoliMix and LixiLan ONE CAN (advancing from basal insulin)., Results: Baseline characteristics were generally similar between 219 users and 746 non-users. Least squares mean changes in HbA 1c from baseline to Week 26 were similar for users (-1.2 % [95 % confidence intervals: -1.4 %, -1.1 %]) and non-users (-1.2 % [-1.2 %, -1.1 %]). Changes in body weight, fasting glucose and post-prandial glucose were similar between groups, as were hypoglycaemic events., Conclusions: Pooled results from three studies of adults with T2D demonstrated that iGlarLixi provided similar clinically meaningful improvements in glycaemic control without increased hypoglycaemia risk, regardless of concomitant use of SGLT2is., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FG: has served as an advisor for Eli Lilly, Medtronic, Novo Nordisk, Roche Diabetes Care and Sanofi; has received payment of honoraria for lectures, presentations, manuscript writing or education events from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Medtronic, Novo Nordisk, Roche Diabetes Care and Sanofi; has patents planned, issued or pending for Roche Diabetes Care; has served as a research investigator for Eli Lilly, Novo Nordisk and Roche Diabetes Care, and has received grants from Eli Lilly and Roche Diabetes Care. CG: has participated in scientific advisory boards for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi and has received consulting fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Krka, Merck KGaA, MSD, Novo Nordisk, Sanofi and Servier. HA: Nothing to disclose. FL is an employee of Sanofi; may hold shares and/or stock options. LMM: Employee of Ividata Life Sciences, Levallois-Perret, France, contracted by Sanofi. JR has served on advisory panels for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Hanmi, Intarcia, Novo Nordisk, Oramed, Sanofi, Structure Therapeutics, Terns Pharma and Zealand, and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Intarcia, Merck, Novo Nordisk, Oramed, Pfizer and Sanofi., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate safety and effectiveness of iGlarLixi in adults with type 2 diabetes mellitus (T2DM) observing fast during Ramadan from Gulf countries., Methods: This planned subgroup analysis of the SoliRam - a multinational, prospective, non-interventional, real-world, observational study - focused on participants from Gulf countries. Primary endpoint was proportion of participants experiencing ≥1 episode of severe and/or symptomatic documented (<70 mg/dL [<3.9 mmol/L]) hypoglycemia., Results: A total of 241 individuals with T2DM (mean age: 58.1 years; male: 54.4%; mean duration of diabetes: 13.3 years) were included. All 234 eligible participants followed during Ramadan were able to fast for ≥25 days and no participants broke fast due to hypoglycemia. Primary endpoint was reported in one participant (0.5%) during fasting hours during Ramadan. Improvements (mean ± SD change) in HbA1c (-1.0 ± 1.0% [-11 ± 10 mmol/mol]), FPG (-22.5 ± 29.7 mg/dL), and body weight (-1.5 ± 2.0 kg) were observed from pre-Ramadan to post-Ramadan. Three participants (1.2 %) reported an adverse event (AE) of any cause and one (0.4%) reported a gastrointestinal AE., Conclusions: iGlarLixi is an effective and well-tolerated treatment in people with T2DM from Gulf countries, including during Ramadan fasting, and is associated with low risk of hypoglycemia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohamed Hassanein reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Sanofi. Adel El Naggar reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Sanofi. Abdulrahman Al Sheikh reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Sanofi. Lydie Melas-Melt reports administrative support, article publishing charges, and writing assistance were provided by Sanofi. Saud AlSifri reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Sanofi. Mohamed Hassanein reports a relationship with Sanofi, Boehringer Ingelheim, and Novo Nordisk that includes: board membership. Mohamed Hassanein reports a relationship with Sanofi, Novo Nordisk, Eli Lilly and Company, Merck Sharp and Dohme, Janssen, and LifeScan that includes: speaking and lecture fees. Adel El Naggar reports a relationship with Sanofi, Novo Nordisk, and Merck & Co that includes: board membership. Adel El Naggar reports a relationship with Sanofi, Novo Nordisk, AstraZeneca, MSD, Organon & Co., Boehringer Ingelheim, Eli Lilly and Company, and Novartis that includes: speaking and lecture fees. Khier Djaballah reports a relationship with Sanofi that includes: employment and equity or stocks. Mohamed Saeed reports a relationship with Sanofi that includes: employment. Lydie Melas-Melt reports a relationship with IVIDATA Life Sciences that includes: employment. Saud AlSifri reports a relationship with Sanofi that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: This subanalysis of the SoliMix trial assessed the efficacy and safety of advancing basal insulin (BI) therapy with iGlarLixi versus BIAsp 30 in people with type 2 diabetes (T2D) living in Latin American (LATAM) countries, i.e. Argentina and Mexico (N = 160)., Materials and Methods: SoliMix (EudraCT: 2017-003370-13) was a 26-week, open-label, multicentre study, where adults with T2D suboptimally controlled with BI plus one or two oral glucose-lowering drugs and glycated haemoglobin (HbA1c) ≥7.5% to ≤10% were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy endpoints were non-inferiority in HbA1c reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30., Results: Both primary efficacy endpoints were met in the LATAM region. After 26 weeks, HbA1c was reduced by 1.8% with iGlarLixi and 1.4% with BIAsp 30, meeting non-inferiority [least squares mean difference -0.47% (95% confidence interval: -0.82, -0.11); p < .001]. iGlarLixi was superior to BIAsp 30 for body weight change [least squares mean difference -1.27% (95% confidence interval: -2.41, -0.14); p = .028]. iGlarLixi was also superior to BIAsp 30 for HbA1c reduction (p = .010). A greater proportion of participants achieved HbA1c <7% without weight gain and HbA1c <7% without weight gain and without hypoglycaemia with iGlarLixi versus BIAsp 30. Incidence and rates of American Diabetes Association Level 1 and 2 hypoglycaemia were lower with iGlarLixi versus BIAsp 30., Conclusions: Once-daily iGlarLixi provided better glycaemic control with weight benefit and less hypoglycaemia than twice-daily premix BIAsp 30. iGlarLixi may be a favourable alternative to premix BIAsp 30 in people with suboptimally controlled T2D to advance BI therapy in the LATAM region., (© 2023 Sanofi Group and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics., Methods: SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function., Results: No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P > 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P = 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events., Conclusions: Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Patient-reported outcomes are increasingly used in the management of patients with multiple sclerosis to understand the patient's perspective of disease and treatment. These measures provide insights into important factors including treatment satisfaction, physical and psychological function, and quality of life., Objective: To present results from the real-world PRO-ACT study in patients with multiple sclerosis who switched to alemtuzumab from another disease-modifying therapy., Methods: This 24-month, prospective, multicenter, observational study had a primary endpoint of change in overall satisfaction, measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4. Secondary endpoints included the Multiple Sclerosis Impact Scale-29 (MSIS-29), Modified Fatigue Impact Scale-5 (MFIS-5), and the Patient-Determined Disease Steps (PDDS). Safety was monitored with adverse events (AEs)., Results: Of 199 enrolled patients, improvements were observed in mean TSQM scores for overall satisfaction (baseline, 50.3; year 2, + 13.2; p   <  0.0001), effectiveness (49.3 and + 12.2; p   <  0.0001), and side effects (77.6 and + 4.5; p   =  0.04). Improvements were also observed in MSIS-29 physical (52.4 and -6.0; p   <  0.0001), MSIS-29 psychological (53.4 and -7.0; p   =  0.0003), and MFIS-5 (12.8 and -1.7; p   <  0.0001). Most (95.0%) patients experienced ≥ 1 AE (88.4% mild, 67.8% moderate)., Conclusions: The primary endpoint was met; the safety of alemtuzumab was consistent with pivotal studies., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SW reports receiving consulting, principal investigator, and/or speaking fees (Alkermes, Biogen, Celgene, Genentech, Novartis, Sanofi, and TG Therapeutics). FJ reports receiving honoraria for giving presentations, advisory board participation, research funding, and for an infusion clinic (Biogen, Merck Serono, Novartis, Roche, and Sanofi). TAM reports receiving speaking and/or consulting fees (Abbvie, Amgen, Biogen, Biohaven, BMS, Genentech, Lundbeck, Novartis, Reven, Sanofi, and Teva) and research support (Abbvie, Biogen, BMS, Celgene, Elan, EMD Serono, Genentech, Hoffman-La Roche, Ipsen, Merck, Novartis, Sanofi, and Teva). JAN reports receiving research grants (Biogen Idec, Genentech, Novartis, and PCORI) and consulting and/or speaking fees (Alexion, Bristol Myers Squib, EMD Serono, Genentech, Greenwich Biosciences, Novartis, Sanofi, and Viela Bio). RA reports receiving speaking fees from and advisory board participation for Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva. LT reports receiving consulting fees (Acorda, Biogen Idec, EMD Serono, Mallinckrodt, Novartis, Pfizer, and Sanofi), and grant/research support (Biogen, EMD Serono, and Sanofi). BK reports consulting/honorarium (Acorda, Alexion, Biogen, Celgene, Genentech, Novartis, Sanofi, Serono, and Teva); contracted research (Alexion, Biogen, Genentech, Novartis, Ra Pharmaceuticals, and Sanofi). MC, RG, NR, and AMR are employees of Sanofi and may hold shares and/or stock options in the company. AR and LMM were employees of Sanofi at the time the study was conducted, and are currently employees of Ividata Life Sciences. SFH reports receiving consulting agreements, speaker honoraria, and grant/research financial support (AbbVie, Adamas, Alexion, Atara, Avanir, Biogen, Janssen, Mallinckrodt, Novartis, Osmotica, Roche, and Sanofi)., (© The Author(s), 2022.)

The relationship between baseline fasting C-peptide (FCP) and glucose control was examined in insulin-naïve people with type 2 diabetes inadequately controlled with oral antihyperglycaemic drugs commencing basal insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) in the absence of sulfonylurea/glinides. Participants with FCP measurement from the EDITION 3 trial (n = 867) were stratified according to baseline FCP (≤0.40, >0.40-1.20, >1.20 nmol/L); 11.0%, 70.9% and 18.1% contributed to each group. Glycaemic control, body weight, insulin dose and hypoglycaemia were determined at 26 weeks. Glycaemic control (HbA1c, FPG) at 26 weeks was similar in each FCP group between insulins. However, end-of-study insulin dose was greater with higher FCP for both insulins. More people with lower baseline FCP experienced hypoglycaemia with both insulins, but with numerically lower incidence for Gla-300 versus Gla-100 across all FCP groups for all definitions (time periods and levels) of hypoglycaemia. This suggests that Gla-300 might be particularly advantageous for people who are at higher risk of hypoglycaemia., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: Chronic kidney disease (CKD) challenges diabetes management and is associated with increased cardiovascular morbidity and mortality. We examined whether clinical outcomes with insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (IDeg-100) are affected by renal function in a prespecified subgroup analysis from the BRIGHT trial., Materials and Methods: BRIGHT (NCT02738151) was a multicentre, open-label, randomized, active-controlled, two-arm, parallel-group, 24-week study in insulin-naïve uncontrolled type 2 diabetes (T2D). Participants were randomized 1:1 to evening Gla-300 (n = 466) or IDeg-100 (n = 463) and stratified based on baseline estimated glomerular filtration rate (eGFR) for this analysis., Results: Heterogeneity of treatment effect across renal function subgroups was observed (P = .02), reflecting a greater mean glycated haemoglobin (HbA1c) reduction from baseline to week 24 with Gla-300 versus IDeg-100 in the eGFR <60 mL/min/1.73 m 2 subgroup (least squares mean difference: -0.43% [95% confidence interval: -0.74% to -0.12%]), while there were no differences in hypoglycaemia incidence or rates over 24 weeks in that subgroup. HbA1c reductions were similar between treatments in the other eGFR subgroups. However, heterogeneity was observed for annualized rates of anytime (24 hours) or nocturnal (00:00-05:59 hours) confirmed hypoglycaemia (≤70 mg/dL [≤3.9 mmol/L]) over 24 weeks showing less hypoglycaemia with Gla-300 versus IDeg-100 in the ≥90 mL/min/1.73 m 2 ., Conclusions: Kidney function seems to affect the glucose-lowering effects of Gla-300 versus IDeg-100 in insulin-naïve T2D. Greater HbA1c reductions with Gla-300 without increase in hypoglycaemia risk, were observed in patients with eGFR <60 mL/min/1.73 m 2 ., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Allergic rhinitis is a prevalent disease, which can be classed as seasonal (SAR) or perennial. In addition to nasal symptoms, up to 75% of sufferers experience itching, redness, and tearing of the eyes. Intranasal corticosteroids are effective in controlling the allergic nasal symptoms, and increasing evidence suggests that they also can relieve some of the allergic ocular symptoms., Objective: To evaluate the magnitude of efficacy of triamcinolone acetonide (TAA) compared with placebo or fluticasone propionate (FP) on ocular symptom improvement in patients with SAR., Methods: A meta-analysis of summary data from 8 randomized, double- or single-blind trials, assessing mean change in total or individual (tearing, redness, and itching) eye symptoms was conducted. Trials that administered a daily dose of 220 μg TAA vs placebo or 200 μg FP over at least 2 weeks' duration, in patients aged 12 years or older with SAR, were analyzed., Results: Total eye symptom reduction after 2 weeks was greater with TAA than placebo, with a mean treatment difference of -0.32 (95% CI, -0.444 to -0.203). In addition, significant reductions in tearing, but not itching or redness, were observed after TAA treatment compared with placebo. No significant treatment difference was seen between TAA and FP in total ocular symptoms at any of the time points measured (weeks 1, 2, 3, and overall). All treatments exhibited similar safety profiles and were deemed well tolerated., Conclusion: The meta-analysis demonstrated the positive clinical improvements TAA has on total ocular allergy symptoms, especially tearing, in addition to its recognized nasal symptom efficacy in SAR., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To further investigate glycaemic control and hypoglycaemia in BRIGHT, focusing on the titration period., Materials and Methods: BRIGHT was a multicentre, open-label, randomized, active-controlled, two-arm, parallel-group, 24-week study in insulin-naïve patients with uncontrolled type 2 diabetes initiated on glargine 300 U/mL (Gla-300) (N = 466) or degludec (IDeg-100) (N = 463). Predefined efficacy and safety outcomes were investigated during the initial 12-week titration period. In addition, patients' characteristics and clinical outcomes were assessed descriptively, stratified by confirmed (≤3.9 mmol/L) hypoglycaemia incidence during the initial titration period., Results: At week 12, HbA1c was comparable between Gla-300 (7.32%) and IDeg-100 (7.23%), with similar least squares (LS) mean reductions from baseline (-1.37% and - 1.39%, respectively; LS mean difference of 0.02; 95% confidence interval: -0.08 to 0.12). Patients who experienced hypoglycaemia during the initial titration period had numerically greater HbA1c reductions by week 12 than patients who did not (-1.46% vs. -1.28%), and higher incidence of anytime (24 hours; 73.3% vs. 35.7%) and nocturnal (00:00-06:00 hours; 30.0% vs. 11.9%) hypoglycaemia between weeks 13-24., Conclusions: The use of Gla-300 resulted in similar glycaemic control as IDeg-100 during the initial 12-week titration period of the BRIGHT study, when less anytime (24 hours) hypoglycaemia with Gla-300 versus IDeg-100 has been reported. Experiencing hypoglycaemia shortly after initiating Gla-300 or IDeg-100 may be associated with hypoglycaemia incidence in the longer term, potentially impacting glycaemic management., (© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To investigate the impact of renal function on the safety and efficacy of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100)., Materials and Methods: A meta-analysis was performed using pooled 6-month data from the EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged ≥18 years with a diagnosis of type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300 or Gla-100. Pooled results were assessed by two renal function subgroups: estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m 2 ., Results: The decrease in glycated haemoglobin (HbA1c) after 6 months and the proportion of individuals with T2DM achieving HbA1c targets were similar in the Gla-300 and Gla-100 groups, for both renal function subgroups. There was a reduced risk of nocturnal (12:00-5:59 am) confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 in both renal function subgroups (eGFR <60 mL/min/1.73 m 2 : relative risk [RR] 0.76 [95% confidence interval {CI} 0.62-0.94] and eGFR ≥60 mL/min/1.73 m 2 : RR 0.75 [95% CI 0.67-0.85]). For confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycaemia at any time of day (24 hours) the hypoglycaemia risk was lower with Gla-300 vs Gla-100 in both the lower (RR 0.94 [95% CI 0.86-1.03]) and higher (RR 0.90 [95% CI 0.85-0.95]) eGFR subgroups., Conclusions: Gla-300 provided similar glycaemic control to Gla-100, while indicating a reduced overall risk of confirmed (≤3.9 and <3.0 mmol/L [≤70 and <54 mg/dL]) or severe hypoglycaemia, with no significant difference between renal function subgroups., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To assess the impact of duration of prior basal insulin therapy on study outcomes in people with type 2 diabetes mellitus receiving insulin glargine 300 U/mL (Gla-300) or insulin glargine 100 U/mL (Gla-100) for 6 months., Methods: A post hoc patient-level meta-analysis of data from the EDITION 1 and 2 studies. Outcomes included: HbA 1c , percentage of participants with ≥1 confirmed or severe hypoglycaemic event at night (00:00-05:59 h) or any time (24 h), and body weight change. Data were analysed according to duration of prior basal insulin use: >0-≤2 years, >2-≤5 years, >5 years., Results: This meta-analysis included 1618 participants. HbA 1c change from baseline to month 6 was comparable between Gla-300 and Gla-100 groups, regardless of duration of prior basal insulin therapy. The lower risk with Gla-300 versus Gla-100 of ≥1 confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic event, at night or any time (24 h), was unaffected by duration of prior basal insulin therapy. Similarly, weight change was unaffected by duration of prior basal insulin therapy., Conclusions: Switching to Gla-300 from other basal insulin therapies provided comparable glycaemic control with lower risk of hypoglycaemia versus Gla-100, regardless of duration of prior basal insulin therapy., Clinical Trial Registration: NCT01499082, NCT01499095 (ClinicalTrials.gov)., (Copyright © 2018. Published by Elsevier B.V.)

Most of the existing data on real-life management of bipolar disorder are from studies conducted in western countries (mostly United States and Europe). This multinational, observational cohort study aimed to describe the management and clinical outcomes of bipolar patients in real-life conditions across various intercontinental countries (Bangladesh, Egypt, Iran, Israel, Tunisia, and Ukraine). Data on socio-demographic and disease characteristics, current symptomatology, and pharmacological treatment were collected. Comparisons between groups were performed using standard statistical tests. Overall, 1180 patients were included. The median time from initial diagnosis was 80 months. Major depressive disorder was the most common initial diagnosis. Mood stabilizers and antipsychotics were the most common drugs being prescribed at the time of the study. Antidepressants (mainly selective serotonin uptake inhibitors [SSRIs]) were administered to 36.1% of patients. Patients with bipolar I disorder received higher number of antipsychotics and anxiolytics than those with bipolar II disorder (p < 0.001). Presence of depressive symptoms was associated with an increase in antidepressant use (p < 0.001). Bipolar disorder real-life management practice, irrespective of region, shows a delay in diagnosis and an overuse of antidepressants. Clinical decision-making appears to be based on a multidimensional approach related to current symptomatology and type of bipolar disorder.