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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.)

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.)

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.)