Aim To compare the efficacy and safety of self‐ versus physician‐managed titration of insulin glargine 300 U/mL (Gla‐300) in people with inadequately controlled type 2 diabetes. Methods Take Control (EudraCT number: 2015‐001626‐42) was a 24‐week, multi‐national, open‐label, controlled, two‐arm, parallel‐group study in insulin‐naïve and pre‐treated participants, randomized 1:1 to a self‐ or physician‐managed titration of Gla‐300. The fasting self‐monitored plasma glucose (SMPG) target was 4.4 to 7.2 mmol/L. The primary outcome was non‐inferiority of glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary outcomes included SMPG target achievement without hypoglycaemia, hypoglycaemia incidence, adverse events and participant‐reported outcomes (PROs). Results At week 24, the least squares (LS) mean HbA1c reduction was 0.97% (10.6 mmol/mol) and 0.84% (9.2 mmol/mol) in the self‐ and physician‐managed groups, respectively, with an LS mean difference of −0.13% [95% confidence interval −0.2619 to −0.0004] (–1.4 mmol/mol [–2.863 to –0.004]), demonstrating non‐inferiority (P < 0.0001) and superiority (P = 0.0247) of self‐ versus physician‐managed titration. Significantly more of the self‐ than physician‐managed group achieved SMPG target without hypoglycaemia (67% vs 58%; P = 0.0187). Overall, hypoglycaemia incidence was similar in each group. No safety concerns were reported. In both groups, similar PRO improvements were observed for distress related to diabetes disease burden and for confidence in diabetes self‐management, with even more individuals achieving a clinically relevant reduction in emotional burden and fewer individuals with high emotional burden in the self‐managed group. Conclusions Self‐managed titration of Gla‐300 was superior to physician‐managed titration in terms of HbA1c reduction, accompanied by similar total PRO scores, with a clinically relevant reduction in emotional burden, and similar hypoglycaemia frequency.

Aim: To report the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) versus standard-of-care basal insulin analogues (SOC-BI) at 12 months in the ACHIEVE Control trial, which is a prospective pragmatic randomized real-life study in insulin-naïve adults with type 2 diabetes (T2D). Methods: A total of 3304 insulin-naïve adults with T2D and glycated haemoglobin (HbA1c) concentration of 64 to 97 mmol/mol (8.0% to 11.0%) after ≥1 year of treatment with two or more antihyperglycaemic agents were randomized to Gla-300 or SOC-BI. Key secondary endpoints included HbA1c target attainment without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at 12 months. Results: At 12 months, 26.1% (Gla-300) and 23.7% (SOC-BI) of adults achieved HbA1c targets without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.97-1.35); 33.0% and 29.5%, respectively, achieved HbA1c targets without documented symptomatic (<3.0 mmol/L [<54 mg/dL]) or severe hypoglycaemia (OR 1.19, 95% CI 1.02-1.38). The OR for HbA1c target achievement was 1.15 (95% CI 0.99-1.34), and favoured Gla-300 versus SOC-BI for absence of documented symptomatic or severe hypoglycaemia at 12 months for both ≤3.9 mmol/L (≤70 mg/dL; OR 1.21, 95% CI 1.05-1.40) and < 3.0 mmol/L (<54 mg/dL; OR 1.26, 95% CI 1.07-1.48). Conclusion: Gla-300 tended to be associated with lower hypoglycaemia risk than SOC-BI in real-world clinical practice during the 12-month follow-up.

Aims: To compare the safety and efficacy of insulin glargine 300 U/mL (Gla-300) versus first-generation standard-of-care basal insulin analogues (SOC-BI; insulin glargine 100 U/mL or insulin detemir) at 6 months. Methods: In the 12-month, open-label, multicentre, randomized, pragmatic ACHIEVE Control trial, insulin-naïve adults with type 2 diabetes (T2D) and glycated haemoglobin (HbA1c) 64 to 97 mmol/mol (8.0%-11.0%) after ≥1 year of treatment with ≥2 diabetes medications were randomized to Gla-300 or SOC-BI. The composite primary endpoint, evaluated at 6 months, was the proportion of participants achieving individualized HbA1c targets per Healthcare Effectiveness Data and Information Set (HEDIS) criteria without documented symptomatic (blood glucose ≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at any time of the day at 6 months. Results: Of 1651 and 1653 participants randomized to Gla-300 and SOC-BI, respectively, 31.3% and 27.9% achieved the composite primary endpoint at 6 months (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01-1.39; P = 0.03 for superiority); 78.4% and 75.3% had no documented symptomatic or severe hypoglycaemia (OR 1.19, 95% CI 1.01-1.41). Changes from baseline to month 6 in HbA1c, fasting plasma glucose, weight, and BI analogue dose were similar between groups. Conclusions: Among insulin-naïve adults with poorly controlled T2D, Gla-300 was associated with a statistically significantly higher proportion of participants achieving individualized HEDIS HbA1c targets without documented symptomatic or severe hypoglycaemia (vs SOC-BI) in a real-life population managed in a usual-care setting. The ACHIEVE Control study results add value to treatment decisions and options for patients, healthcare providers, payers and decision makers.

ACHIEVE Control, a pragmatic randomized real-world clinical trial, prospectively compared the effectiveness and safety of Gla-300 vs. SoC-BIs (glargine 100 U/mL and detemir) in a broad primary care and specialist population of insulin-naive patients with A1C ≥8% despite using ≥2 antihyperglycemia agents for ≥1 year. The pre-specified 6-month outcomes showed superiority of Gla-300 in achieving the composite primary endpoint: 31.3% of patients using Gla-300 (vs. 27.9% of patients using SoC-BIs; p=0.03) attained individualized HEDIS A1C targets (A1C &lt;8% if age ≥65 years or with defined comorbidities; A1C &lt;7% otherwise) without severe (requiring external assistance) and/or symptomatic documented hypoglycemia (≤70 mg/dL). We report 12-month outcomes, which provide valuable insights on longer-term effectiveness and safety. At 12 months, 26.1% of patients using Gla-300 (vs. 23.7% using SoC-BIs) met the composite endpoint (odds ratio [OR] 1.14, 95% CI 0.97-1.35), and more attained HEDIS A1C targets without ADA-defined clinically significant (Level 2) hypoglycemia (&lt;54 mg/dL) with Gla-300 vs. SoC-BIs (33.0% vs. 29.5%; OR 1.19, CI 1.02-1.38]). A1C reductions seen at 6 months were maintained to 12 months and comparable in patients using Gla-300 vs. SoC-BIs (mean change from baseline: -1.31% vs.-1.26%; nominal p=0.325). Similar mean changes from baseline in body weight (Gla-300: +1.55kg; SoC-BIs: +1.39kg) and insulin dose (+0.22 U/kg; both groups) were observed at 12 months. Drug-related treatment-emergent adverse events were similar across groups. In summary, the 12-month analysis of the ACHIEVE Control study translated the findings of improved clinical outcomes for Gla-300 vs. SoC-BIs previously seen in randomized controlled trials to a broader real-world population managed in a usual care setting. Disclosure L. Meneghini: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Sanofi-Aventis. Consultant; Self; Sanofi-Aventis. Other Relationship; Self; American Diabetes Association. J. Gill: Employee; Self; Sanofi. A. Dauchy: None. A. Bacevicius: Employee; Self; Sanofi. J. Strong: Advisory Panel; Self; Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Abbott, American Diabetes Association, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker's Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. Funding Sanofi

Background Atrial fibrillation (AF) is a marker of risk in patients presenting with acute coronary syndromes (ACS). The potential effect of inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) on the incidence of AF is unknown. Methods The ODYSSEY OUTCOMES trial compared randomized treatment with the PCSK9 inhibitor alirocumab or placebo in patients with recent ACS and residual dyslipidaemia despite optimal statin therapy. The current analysis determined: 1) whether alirocumab treatment influenced incident AF; 2) whether a history of AF influenced the risk of major adverse cardiovascular events (MACE); and 3) whether there was interaction between AF at baseline and randomized treatment on MACE. AF was determined from the medical history and investigator reports of adverse events. Results Of 18,924 participants, 662 (3.5%) had a history of AF at randomization and 18,262 (96.5%) had no history of AF. Of the latter category, 499 (2.7%) had incident AF. Older age, randomization in South America or Eastern Europe, history of heart failure or myocardial infarction, and higher body mass index were factors associated with incident AF. Treatment with alirocumab or placebo did not influence incident AF (2.2% vs 2.6%, respectively; hazard ratio 0.90, 95% confidence interval 0.75–1.08; Figure). Patients with a history of AF had a greater burden of comorbidities, including cerebrovascular disease, peripheral artery disease, hypertension and heart failure; they also had higher rates of MACE (Table). There was no significant interaction between AF and randomized treatment on risk of MACE (P interaction=0.78) Conclusions Although treatment with alirocumab did not significantly modify the risk of incident AF after ACS in this analysis, future studies with more sensitive and systematic methods of ascertainment may be warranted. History of AF is a strong predictor of risk of recurrent MACE after ACS. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi, Regeneron Pharmaceuticals, Inc