Self-monitored Plasma Glucose Research Articles

799-P: Predictors of Glycemic Control by Derived Time in Range for People with Type 2 Diabetes Advancing with iGlarLixi—A Pooled Analysis

This post-hoc, pooled analysis of 3 randomized controlled trials aimed to identify factors associated with achieving a derived Time in Range (dTIR) ≥70% at the end of treatment (EOT) with iGlarLixi in people with type 2 diabetes (T2D). dTIR was calculated from 7-point self-monitored plasma glucose (SMPG) profiles and assessed at baseline (BL) and EOT for people with T2D advancing from oral (LixiLan-O), insulin (LixiLan-L), or GLP-1 RA (LixiLan-G) therapy to once-daily iGlarLixi. Participants at EOT were classified as either achieving or not achieving dTIR ≥70%, and corresponding predictive BL characteristics were analyzed with univariable and multivariable stepwise logistic regression. Analyses (N=880) showed that 86% of participants achieved dTIR ≥70% with iGlarLixi; T2D duration and HbA1c at BL were greater in those with dTIR <70% (mean [SD] 11.35 [7.31] years and 8.26 [0.68] %) than those with dTIR ≥70% (10.40 [6.51] years and 7.96 [0.68] %), respectively. Post-meal SMPG at BL was higher in those not achieving dTIR ≥70%. Lower BL HbA1c (p=0.0205), BL insulin dose (p<0.0001), and hypoglycemia level 2 frequency (p=0.0139 for 1-3 vs 0 events; p=0.0172 for ≥4 vs 0) were predictors of attaining dTIR ≥70% (Table). HbA1c, insulin dose, and hypoglycemia frequency at BL were predictors of achieving target dTIR ≥70% in people with T2D advancing therapy with iGlarLixi. Disclosure I.Hramiak: Research Support; Eli Lilly and Company, Novo Nordisk, Sanofi, Speaker's Bureau; Canadian Medical & Surgical Knowledge Translation Research Group (CMS), Insulet Corporation, Medtronic, Merck & Co., Inc., Bayer Inc. J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. H.Aydin: Advisory Panel; Sanofi, Novo Nordisk, Boehringer Ingelheim Inc., Speaker's Bureau; Novo Nordisk. F.Lauand: Employee; Sanofi. L.Melas-melt: None. E.Souhami: Employee; Sanofi, Stock/Shareholder; Sanofi. M.Haluzik: Advisory Panel; Novo Nordisk, Lilly Diabetes, Boehringer-Ingelheim, Research Support; Sanofi, Speaker's Bureau; Abbott, AstraZeneca. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. Funding Sanofi

775-P: Predictors of Glycemic Control in Older People with Type 2 Diabetes Treated with iGlarLixi—A Pooled Analysis

For older adults (>65 years) with type 2 diabetes (T2D), iGlarLixi can be a simple and effective therapeutic option. We aimed to identify factors associated with achieving target HbA1c <7% and derived Time in Range (dTIR) ≥70% in this population in response to once daily iGlarLixi. This post-hoc, pooled analysis of 4 randomized trials included 465 people advancing from oral (LixiLan-O), GLP-1 RA (LixiLan-G), or insulin (LixiLan-L; SoliMix) therapies to iGlarLixi for 26 or 30 weeks. HbA1c and dTIR responses were assessed at baseline (BL) and end of treatment (EOT) for each participant and classified as attained (<7.0% or dTIR ≥70%) or unattained (≥7.0% or <70%). dTIR was calculated from 7-point self-monitored plasma glucose profiles from the three LixiLan studies (LixiLan-O. G, and L). Potential predictive factors were analyzed by univariable and multivariable stepwise logistic regression. Overall, 60% of participants achieved HbA1c <7.0% and 87.5% achieved dTIR ≥70%. Predictors of attained HbA1c response (p<0.05) included lower BL HbA1c and lower BL insulin dose. Predictor of attained dTIR response (p<0.05) was higher BL fasting plasma glucose (FPG; Table), while sex, T2D duration, and obesity had no predictive value. To conclude, in older people with T2D treated with iGlarLixi, consideration of BL HbA1c and FPG, as well as BL insulin dose may improve achieving individualized glycemic targets. Disclosure M.Munshi: Consultant; Sanofi. R.Ritzel: Consultant; Novo Nordisk, Sanofi, Speaker's Bureau; Novo Nordisk, Sanofi, Pfizer Inc., Merck Sharp & Dohme Corp., Lilly. R.J.Mccrimmon: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk A/S. I.Hramiak: Research Support; Eli Lilly and Company, Novo Nordisk, Sanofi, Speaker's Bureau; Canadian Medical & Surgical Knowledge Translation Research Group (CMS), Insulet Corporation, Medtronic, Merck & Co., Inc., Bayer Inc. F.Lauand: Employee; Sanofi. L.Melas-melt: None. E.Souhami: Employee; Sanofi, Stock/Shareholder; Sanofi. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. Funding Sanofi

Efficacy and Safety of Insulin Glargine 300U/mL in People with Type2 Diabetes Uncontrolled on Basal Insulin: The 26-Week Interventional, Single-Arm ARTEMIS-DM Study.

IntroductionThe efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa.MethodsThe ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5–10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed.ResultsA total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (− 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event.ConclusionIn people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions.ClinicalTrials.gov identifierNCT03760991.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01271-7.

A Real-World Observational Study of Gla-300 in Adults with Type 2 Diabetes Who Fast During Ramadan in the South Asia Region: A Subgroup Analysis of the ORION Study

IntroductionIn this ORION study subgroup analysis, the safety and effectiveness of insulin glargine 300 U/mL (Gla-300) was evaluated in people from the South Asia region with type 2 diabetes mellitus (T2DM) before, during, and after Ramadan, in a real-world setting.MethodsThe ORION study was a real-world, prospective, observational, non-comparative study conducted across 11 countries. The current subgroup analysis included participants from the South Asia region (India and Pakistan) who fasted during Ramadan. The primary endpoint was the percentage of participants experiencing ≥ 1 event of severe and/or symptomatic documented hypoglycemia with self-monitored plasma glucose (SMPG) ≤ 70 mg/dL during Ramadan. Secondary endpoints analyzed were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), SMPG, insulin dose, and adverse events (AEs).ResultsThis subgroup analysis included 106 participants from the South Asia region with mean (standard deviation) age of 51.3 (10.9) years and mean number of 29.8 (4.0) fasting days. The number of severe and/or symptomatic documented hypoglycemia events was low in the pre-Ramadan (SMPG ≤ 70 mg/dL: 1 event [0.9%]; SMPG < 54 mg/dL: 1 event [0.9%]) and Ramadan periods (SMPG ≤ 70 mg/dL: 1 event [0.9%]; SMPG < 54 mg/dL: 0 events), and none in the post-Ramadan period. One participant reported severe hypoglycemia (any time of the day: nocturnal or daytime) throughout the pre-Ramadan period. A reduction in HbA1c and FPG levels was seen during the pre- to post-Ramadan period; however, a slight increase in SMPG levels was reported during this same period. Gla-300 daily dose was reduced from 21.6 (9.6) U to 20.2 (8.9) U during the pre-Ramadan to Ramadan period. The incidence of AEs was 1.9%.ConclusionsThe real-world data from the ORION study indicate that Gla-300 is effective, with low risk of hypoglycemia, for the management of T2DM during Ramadan in the South Asian population.Trial RegistrationCTRI/2019/02/017636.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01234-y.

Safety and Effectiveness of Insulin Glargine 300 U/mL in Participants with Type 2 Diabetes Who Fast During Ramadan in The Gulf Region: A Subgroup Analysis of the Real-World ORION Study.

IntroductionTo evaluate the safety and effectiveness of insulin glargine 300 U/mL (Gla-300) in people with type 2 diabetes mellitus (T2DM) in the Gulf region who fast during Ramadan.MethodsORION was a real-world, prospective, observational study in people with T2DM treated with Gla-300 during pre-Ramadan, Ramadan, and post-Ramadan periods. This subgroup analysis included 222 participants from the Gulf region (Kuwait, Saudi Arabia, United Arab Emirates, and Qatar). The primary endpoint was the percentage of participants experiencing severe and/or symptomatic documented hypoglycemia (self-monitored plasma glucose [SMPG] ≤ 70 mg/dL) during Ramadan. Changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), SMPG, body weight, insulin dose, and adverse events (AEs) were also evaluated.ResultsThe primary endpoint was reported in one (0.5%) participant during Ramadan. The incidence rate of symptomatic documented hypoglycemia (SMPG ≤ 70 mg/dL) decreased from the pre-Ramadan (3.2%) to Ramadan period (0.5%), and no severe hypoglycemia events were reported during the study. Reductions were observed in HbA1c (mean ± standard deviation: − 0.51 ± 0.95% [− 5.5 ± 10.4 mmol/mol]), FPG (− 13.9 ± 47.5 mg/dL), and SMPG (− 6.1 ± 27.1 mg/dL). No significant changes were observed in body weight or Gla-300 dose. AEs were reported in 11 (5.0%) participants.ConclusionIn a real-world setting in the Gulf region, Gla-300 treatment in people with T2DM during Ramadan was associated with a low incidence of hypoglycemia and improved glycemic control.Trial RegistrationCTRI/2019/02/017636.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01225-z.

Glycaemic variability in patients with type 2 diabetes mellitus treated with dulaglutide, with and without concomitant insulin: Post hoc analyses of randomized clinical trials.

AimTo investigate the association between treatment with dulaglutide and glycaemic variability (GV) in adult patients with type 2 diabetes mellitus (T2D).Materials and MethodsPost hoc analyses of six randomized, phase 3 studies were conducted to investigate the association between treatment with dulaglutide 1.5 mg once weekly and GV in adult patients with T2D. Using data from seven‐ and eight‐point self‐monitored plasma glucose (SMPG) profiles over up to 28 weeks of treatment, GV in within‐ and between‐day SMPG, and between‐day fasting glucose from SMPG (FSMPG) was assessed according to standard deviation and coefficient of variation.ResultsPooled data from five studies with dulaglutide as monotherapy or added to oral glucose‐lowering medication, without concomitant insulin treatment, revealed clinically meaningful reductions in within‐ and between‐day SMPG, and between‐day FSMPG variability from baseline in the dulaglutide group. Comparisons between treatment groups in two studies demonstrated that reductions from baseline in within‐day and between‐day SMPG, and between‐day FSMPG variability were greater for treatment with dulaglutide compared with insulin glargine, as well as for treatment with dulaglutide when added to insulin glargine compared with insulin glargine alone.ConclusionsIn patients with T2D, treatment with dulaglutide as monotherapy or added to oral glucose‐lowering medication, without concomitant insulin treatment, was potentially associated with a reduction in GV. Treatment with dulaglutide was associated with a reduction in GV to a greater degree than insulin glargine. When added to insulin glargine, treatment with dulaglutide was associated with greater decreases in GV compared with insulin glargine alone. As reduced GV may be associated with better outcomes, these findings may have clinical relevance.

Efficacy and safety of iGlarLixi versus IDegLira in adults with type 2 diabetes inadequately controlled by glucagon-like peptide-1 receptor agonists: a systematic literature review and indirect treatment comparison.

To estimate the relative treatment effect between the fixed-ratio combinations iGlarLixi and IDegLira (glucagon-like peptide 1 receptor agonist with basal insulin) in people with type 2 diabetes inadequately controlled on a glucagon-like peptide 1 receptor agonist. A systematic literature review of randomized controlled trials followed by an indirect treatment comparison was performed to compare the efficacy and safety of the available fixed-ratio combinations. Main outcomes were glycated haemoglobin (HbA1c) change and target achievement [<6.5% and <7.0% (<48 and <53 mmol/mol)], fasting plasma glucose, self-monitored plasma glucose, body weight, and incidence and rate of hypoglycaemia. From 4850 abstracts screened, 78 qualified for full-text article review and two randomized controlled trials were included. Baseline characteristics were similar in the two studies. The mean difference at 26 weeks between IDegLira and iGlarLixi was -0.36 (95% credible intervals -0.58, -0.14) % [-3.9 (-6.3, -1.5) mmol/mol] for HbA1c and -1.0 (-1.6, -0.4) mmol/L for fasting plasma glucose. No significant differences were found in HbA1c target attainment, preprandial or postprandial self-monitored plasma glucose, or body weight change. Formal comparisons of hypoglycaemia were limited by differences in definitions between the studies: in non-sulphonylurea users, incidence was 28% for IDegLira ('confirmed' at ≤3.1 mmol/L); for iGlarLixi, incidence was 9% ('documented symptomatic' at <3.0 mmol/L). Results of this indirect treatment comparison using two studies suggest iGlarLixi and IDegLira appear to offer similar benefits for HbA1c target achievement. However, the findings suggest differences in other glycaemia results and hypoglycaemia, which may reflect differences in study design and titration approaches.

1056-P: Effect of Dulaglutide on Glycemic Variability: Post Hoc Analysis of the AWARD Studies

Glycemic variability (GV) may contribute to the development and progression of cardiovascular complications. This post-hoc analysis assessed GV in people with type 2 diabetes, treated with once-weekly dulaglutide (DU), and not receiving any concomitant insulin treatment. Analysis included pooled data from 5 randomized, parallel-arm, phase 3 studies (AWARD 1,2,3,6 and 8). The participants (N=1114, 48% male) received DU 1.5 mg without any concomitant insulin for 26 weeks and with evaluable GV measurements at baseline and study endpoint (week 26). The measurements included within-day and between-day GV calculated by standard deviation (SD) and coefficient of variation (CV) from self-monitored plasma glucose (SMPG), and between-day fasting self-monitored plasma glucose (FSMPG) values. At baseline, the mean (SD) age was 55.9 (9.7) years, BMI 32.7 (5.2) kg/m2, HbA1c 8.0 (0.9) % and fasting plasma glucose 166.5 (47.8) mg/dL. At 26 weeks, DU significantly reduced within-day and between-day GV from SMPG values (SD values, p&amp;lt;0.001, Figure) and between-day GV from FSMPG (p&amp;lt;0.001). SMPG GV changes were significant and consistent across studies. Analysis by CV gave consistent results (Figure). Overall, the analysis suggests that treatment with once-weekly DU 1.5 mg reduces within-day and between-day GV from SMPG and between-day GV from FSMPG. Disclosure E. Jodar: Other Relationship; Self; Elli Lilly &amp; Co, Novo Nordisk, MSD, Lilly, Janssen, Pfizer, AstraZeneca, Sanofi, UCB, Amgen, FAES, Shire, Mundipharma, Novartis. Q. Wang: Employee; Self; Eli Lilly and Company. I. Romera: Employee; Self; Eli Lilly and Company. E. Caveda: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L. Garcia: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company

959-P: Indirect Treatment Comparison (ITC) of IGlarLixi vs. IDegLira in Adults Inadequately Controlled by GLP-1 Receptor Agonists (GLP-1RAs)

In people with type 2 diabetes uncontrolled by GLP-1 RAs, fixed-ratio combination (FRC; basal insulin + GLP-1 RA) is a recommended option. A PICO-framework systematic review of RCTs followed by an ITC was performed to compare the efficacy and safety of the FRCs iGlarLixi (insulin glargine 100 U/mL + lixisenatide) and IDegLira (insulin degludec + liraglutide) in this population. A fixed effects model was used on the two eligible RCTs. Outcomes: change from baseline to week 26 in HbA1c, clinic fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG), and body weight; proportion achieving HbA1c &amp;lt;6.5 or &amp;lt;7.0 %; hypoglycemia incidence. Baseline characteristics were similar across studies. Significant mean differences were seen in change in HbA1c and FPG favoring IDegLira, but not pre- or postprandial SMPG (breakfast or daily average) or weight (Table). Similar proportions achieved HbA1c targets. Hypoglycemia comparisons suffered from varying definitions, sulfonylurea (SU) use and eligibility, and few events in the GLP-1 RA arms (incidence: 32% [confirmed ≤3.1 mmol/L, 28% without SU] with IDegLira and 9% or 28% [symptomatic &amp;lt;3.0 or ≤3.9 mmol/L] with iGlarLixi). This ITC shows similar FRC HbA1c glycemic target achievement but suggests divergent differences in other glycemia results and hypoglycemia, likely due to different study design and titration application. Disclosure P. Home: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Mundipharma International, Novartis AG, Sanofi. Research Support; Self; GlaxoSmithKline plc., Merck &amp; Co., Inc., Sanofi. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim International GmbH. V.R. Aroda: Consultant; Self; Duke, Novo Nordisk Inc., Sanofi. Employee; Spouse/Partner; Merck &amp; Co., Inc. Research Support; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; IMNE, Medscape. M. Fazeli: None. C. Whittington: Employee; Self; Sanofi US. H. Goswami: None. A. Shaunik: None. M. Pourrahmat: Other Relationship; Self; Sanofi US. L. Blonde: Advisory Panel; Self; AstraZeneca, Gilead Sciences, Inc. Consultant; Self; Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Janssen Scientific Affairs, LLC., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Sanofi. S. Kalra: Advisory Panel; Self; Eli Lilly and Company. Speaker’s Bureau; Self; Novo Nordisk A/S, Sanofi-Aventis. Funding Sanofi

Real-world safety and effectiveness of insulin glargine 300 U/mL in participants with type 2 diabetes who fast during Ramadan: The observational ORION study

AimsORION evaluated the safety and effectiveness of Gla-300 in insulin-treated people with T2DM before, during and after Ramadan, in a real-world setting. MethodsThis prospective, observational study across 11 countries included participants with T2DM treated with Gla-300 in pre-Ramadan, Ramadan and post-Ramadan periods. The primary endpoint was the percentage of participants experiencing ≥1 event of severe and/or symptomatic documented hypoglycaemia with self-monitored plasma glucose (SMPG) ≤70 mg/dL during Ramadan. Secondary endpoints included change in HbA1c and insulin dose and adverse events (AEs). ResultsThe mean ± SD number of fasting days was 30.1 ± 3.2. The percentage of participants experiencing ≥1 event of severe and/or symptomatic documented hypoglycaemia (SMPG ≤70 [<54] mg/dL) was low in the pre-Ramadan (2.2% [0.8%]), Ramadan (2.6% [0%]) and post-Ramadan (0.2% [0%]) periods. No participants reported severe hypoglycaemia during Ramadan or post-Ramadan; one participant reported severe hypoglycaemia in pre-Ramadan. HbA1c fell pre- to post-Ramadan, and Gla-300 daily dose (mean ± SD) was reduced pre-Ramadan to Ramadan (from 25.6 ± 11.9 U/0.32 ± 0.14 U/kg to 24.4 ± 11.5 U/0.30 ± 0.13 U/kg). Incidence of AEs was 5.5%. ConclusionsIn ORION, people with T2DM treated with Gla-300 who fasted during Ramadan had a low risk of severe/symptomatic hypoglycaemia and improved glycaemic control.

Low Blood Glucose Index and Hypoglycaemia Risk: Insulin Glargine 300U/mL Versus Insulin Glargine 100 U/mL in Type 2 Diabetes.

IntroductionWe examined differences in hypoglycaemia risk between insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100) in individuals with type 2 diabetes (T2DM) using the low blood glucose index (LBGI).MethodsDaily profiles of self-monitored plasma glucose (SMPG) from the EDITION 2, EDITION 3 and SENIOR treat-to-target trials of Gla-300 versus Gla-100 were used to compute the LBGI, which is an established metric of hypoglycaemia risk. The analysis also examined documented (blood glucose readings < 3.0 mmol/L [54 mg/dL]) symptomatic hypoglycaemia (DSH).ResultsOverall LBGI in EDITION 2 and SENIOR and night-time LBGI in all three trials were significantly (p < 0.05) lower with Gla-300 versus Gla-100. The largest differences between Gla-300 and Gla-100 were observed during the night. In all three trials, individual LBGI results correlated with the observed number of DSH episodes per participant (EDITION 2 [r = 0.35, p < 0.001]; EDITION 3 [r = 0.26, p < 0.001]; SENIOR [r = 0.30, p < 0.001]). Participants at moderate risk of experiencing hypoglycaemia (defined as LBGI > 1.1) reported 4- to 8-fold more frequent DSH events than those at minimal risk (LBGI ≤ 1.1) (p ≤ 0.009).ConclusionsThe LBGI identified individuals with T2DM at risk for hypoglycaemia using SMPG data and correlated with the number of DSH events. Using the LBGI metric, a lower risk of hypoglycaemia with Gla-300 than Gla-100 was observed in all three trials. The finding that differences in LBGI are greater at night is consistent with previously published differences in the pharmacokinetic profiles of Gla-300 and Gla-100, which provides the physiological foundation for the presented results.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-020-00808-y) contains supplementary material, which is available to authorized users.

Efficacy and safety of insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Asia Pacific insulin-naïve people with type 2 diabetes: The EDITION AP randomized controlled trial.

AimTo compare the efficacy and safety of Gla‐300 versus Gla‐100 in insulin‐naïve people with type 2 diabetes in Asia Pacific.Materials and MethodsIn this open‐label, randomized, active‐controlled, 26‐week study, insulin‐naïve participants with type 2 diabetes inadequately controlled with non‐insulin antihyperglycaemic drugs were randomized (2:1) to Gla‐300 or Gla‐100. The initial daily dose of basal insulin was 0.2 U/kg and was adjusted at least weekly for 8–12 weeks to a target fasting self‐monitored plasma glucose (SMPG) of 4.4–5.6 mmol/L.ResultsOf the 604 participants randomized, 570 (Gla‐300, n = 375; Gla‐100, n = 195) completed the study. Non‐inferiority of Gla‐300 versus Gla‐100 in HbA1c reduction from baseline to week 26 was confirmed. In the Gla‐300 and Gla‐100 groups, 51.1% and 52.2% of participants achieved the HbA1c target of <7.0% (rate ratio [95% CI]: 0.98 [0.84 to 1.14]) and 19.1% and 21.9% achieved the target without hypoglycaemia during the last 12 weeks of treatment (rate ratio [95% CI]: 0.87 [0.63 to 1.20]). Changes in fasting plasma glucose and 24‐hour average eight‐point SMPG were comparable between groups. Incidence of hypoglycaemia at any time of day was similar between treatment groups at week 26, but incidence of any nocturnal hypoglycaemia was numerically lower with Gla‐300 than Gla‐100 over the initial 12‐week titration period and 26‐week on‐treatment period. Rates of adverse events were similar between groups and low for serious adverse events.ConclusionsGlycaemic control of Gla‐300 is non‐inferior to Gla‐100 with a similar or lower incidence and proportion of hypoglycaemia in people with type 2 diabetes in Asia Pacific, reinforcing the results in the global EDITION programme.

Efficacy and safety of lixisenatide as add-on therapy to basal insulin in older adults with type 2 diabetes in the GetGoal-O Study.

BackgroundThis study compared the efficacy and safety of lixisenatide with placebo as add‐on therapy to basal insulin (BI) in adults aged ≥70 years with type 2 diabetes (T2D), with or without moderate renal insufficiency.MethodsThis post hoc analysis evaluated data from non‐frail patients with T2D inadequately controlled on BI with or without oral antidiabetic drugs (n = 108), randomized to once‐daily lixisenatide 20 μg or placebo for 24 weeks (GetGoal‐O Study). The primary endpoint was the change in HbA1c from baseline to Week 24. Secondary endpoints included changes from baseline in fasting plasma glucose, 2‐hour postprandial plasma glucose (PPG), average seven‐point self‐monitored plasma glucose (SMPG), area under the curve for SMPG, daily BI dose, body weight, proportion of patients achieving HbA1c > 0.5%, and composite endpoints. Safety outcomes included the incidence of documented symptomatic hypoglycemia (plasma glucose <60 mg/dL) and gastrointestinal treatment‐emergent adverse events (TEAEs). Outcomes were also analyzed by the occurrence of moderate renal insufficiency.ResultsCompared with placebo, lixisenatide‐treated patients had significantly greater reductions in HbA1c, 2‐hour PPG, average seven‐point SMPG, and body weight. Documented symptomatic hypoglycemia was approximately two‐fold higher in patients treated with placebo than lixisenatide (12.7% vs 5.7%). GI TEAEs occurred more frequently in the lixisenatide‐ than placebo‐treated group (34% vs 9.1%). Moderate renal insufficiency (estimated glomerular filtration rate between ≥30 and <60 mL/min/1.73 m2) did not negatively affect lixisenatide efficacy or safety. A greater proportion of patients treated with lixisenatide than placebo achieved composite endpoints.ConclusionsAdd‐on therapy with lixisenatide in non‐frail patients aged ≥70 years with T2D uncontrolled with BI is effective, safe, and well tolerated and should be considered in this population.

1090-P: Reaching ADA Glycemic Targets without Hypoglycemia during Titration with Gla-300 and IDeg in T2DM: Exploratory Analyses from BRIGHT

Guidelines emphasize achieving glycemic targets without hypoglycemia. BRIGHT demonstrated similar HbA1c reduction and less anytime (24 h) hypoglycemia with insulin glargine 300 U/mL (Gla-300) vs. insulin degludec 100 U/mL (IDeg) during the initial 12-week insulin titration period, in insulin-naïve adults with T2DM. We investigated achievement of ADA-recommended HbA1c and fasting self-monitored plasma glucose (FSMPG) targets without confirmed (≤70 mg/dL) hypoglycemia in the first 12 weeks. BRIGHT was a 24-week, multicenter, open-label, randomized, active-controlled, parallel-group, phase 4 trial. Participants were randomized to Gla-300 (n=466) or IDeg (n=463), titrated to a FSMPG of 80-100 mg/dL (below ADA-recommended FSMPG target of ≤130 mg/dL). A similar proportion of participants at week 8 achieved HbA1c &amp;lt;7% without hypoglycemia in both groups; this proportion was numerically higher with Gla-300 than IDeg at week 12 (16.9% vs. 13.6%). From baseline to week 5, numerically more patients with IDeg achieved FSMPG ≤130 mg/dL without hypoglycemia vs. Gla-300, but from week 6 to 12 this was reversed (Figure). More participants achieved ADA-recommended glycemic targets without hypoglycemia with Gla-300 vs. IDeg during the titration period of BRIGHT. These second-generation basal insulin analogs may allow more aggressive titration after insulin initiation in T2DM. Disclosure R. Roussel: Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson &amp; Johnson Diabetes Institute, Novo Nordisk Inc., Zafgen, Inc. Research Support; Self; AbbVie Inc., Akcea Therapeutics, Allergan, Amgen Inc., AstraZeneca, Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Enanta Pharmaceuticals, Inc., GENFIT, Intarcia Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Oramed Pharmaceuticals, Pfizer Inc., Sanofi, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc. Speaker's Bureau; Self; Merck &amp; Co., Inc., Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Melas-Melt: Consultant; Self; Sanofi. L. Berard: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Abbott, Ascensia Diabetes Care, AstraZeneca, Bayer AG, Becton, Dickinson and Company, Janssen Pharmaceuticals, Inc., LifeScan Canada, Mylan, Novo Nordisk Inc., Sanofi. Research Support; Self; Montmed Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc. A.Y. Cheng: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., mdBriefCase Group Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Funding Sanofi (NCT02738151)

Take Control: A randomized trial evaluating the efficacy and safety of self- versus physician-managed titration of insulin glargine 300 U/mL in patients with uncontrolled type 2 diabetes.

AimTo 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.MethodsTake 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).ResultsAt 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.ConclusionsSelf‐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.

Relative contribution of basal and postprandial hyperglycaemia stratified by HbA1c categories before and after treatment intensification with dulaglutide.

To assess the effect of dulaglutide on the relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) to overall hyperglycaemia across HbA1c categories in patients with type 2 diabetes. Data from five phase 3 studies (N = 673) were pooled to assess the change in relative contributions of BHG and PPHG to overall hyperglycaemia across different HbA1c categories after 6 months of treatment intensification with dulaglutide 1.5 mg as monotherapy or with 1 or 2 oral medication(s) in patients with type 2 diabetes. BHG and PPHG were calculated using the area under the curve (AUC) of 7-point self-monitored plasma glucose concentration profiles. As a secondary objective, relative contribution of BHG and PPHG for dulaglutide versus liraglutide, exenatide BID and insulin glargine was assessed by individual studies at 6 months. In pooled data, after 6 months of treatment intensification with dulaglutide 1.5 mg, there was a significant reduction from baseline in overall hyperglycaemia (AUCoverall ) [(mean ± SE) -466.31 ± 18.32 mg*h/dL (P < 0.001)], BHG (AUCbasal ) [(mean ± SE) -371.46 ± 16.36 mg*h/dL (P < 0.001)] and PPHG (AUCpostprandial ) [(mean ± SE) -94.84 ± 7.97 mg*h/dL (P < 0.001)]. At baseline, relative contributions of BHG increased and PPHG decreased with increasing HbA1c levels. This pattern was maintained at 6 months, even as overall glycaemia improved with decreasing HbA1c values. In patients with type 2 diabetes, dulaglutide reduces HbA1c by lowering both basal and postprandial hyperglycaemia across various HbA1c levels.

Reduced Hypoglycemia and Comparable Efficacy with Insulin Glargine 300 U/ML Versus Insulin Glargine 100 U/ML in Patients with Type 2 Diabetes Achieving Different Levels of Prebreakfast Self-Monitored Plasma Glucose

Objective: To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100) in patients with type 2 diabetes (T2D) who reached prebreakfast self-monitored plasma glucose (SMPG) levels <100 and <130 mg/dL. Methods: This was a post hoc analysis of insulin-naïve (EDITION 3, NCT01676220) and experienced (EDITION 2, NCT01499095) patients with uncontrolled T2D, randomized to 6 months of Gla-300 versus Gla-100 treatment. Endpoints included glycated hemoglobin A1c change, hypoglycemia incidence, and event rates. Separate comparisons were done for patients achieving prebreak-fast fasting glucose of <100 versus ≥100 mg/dL and <130 versus ≥130 mg/dL. Results: Efficacy did not differ significantly between treatments in either study. Overall, basal insulin doses were ~10% higher with Gla-300 versus Gla-100. EDITION 2: overall and documented (≤70 mg/dL) hypoglycemia rates were significantly lower with Gla-300 versus Gla-100 in all SMPG groups except <100 mg/dL; nocturnal hypoglycemia rates were significantly lower with Gla-300 in all SMPG groups. EDITION 3: overall hypoglycemia rates were significantly lower with Gla-300 in patients with SMPG ≥100 mg/dL and those with SMPG <130 mg/dL; documented hypoglycemia rates were significantly lower in all SMPG groups except ≥130 mg/dL. Nocturnal and nocturnal documented hypoglycemia rates did not differ by treatment group. Hypoglycemia incidence did not differ by treatment in any SMPG group. Conclusion: In patients with T2D initiating basal insulin or previously treated for ≥6 months with basal insulin, Gla-300 provides similar efficacy to Gla-100 and reduces risk of hypoglycemia for many patients, despite a ~10% higher insulin dose. Abbreviations: A1C = glycated hemoglobin A1c; ADA = American Diabetes Association; Gla-100 = insulin glargine 100 U/mL; Gla-300 = insulin glargine 100 U/mL; OAD = oral antidiabetes drug; SMPG = self-monitored plasma glucose; T2D = type 2 diabetes

IDegLira Achieved Non-Inferior A1C Reduction, Weight Loss and Fewer Hypoglycemic Episodes While Using a Simple Regimen with Fewer Injections and Dose Adjustments Compared with Basal–Bolus Therapy

This post hoc analysis of DUAL VII evaluated treatment complexity of insulin degludec/liraglutide (IDegLira) vs. basal-bolus (BB) therapy in terms of the number of injections and dose adjustments. In the 26-week, open-label trial, patients with type 2 diabetes uncontrolled on metformin and 20-50U insulin glargine 100 U/mL (IG) were randomized 1:1 to IDegLira (n=252) or BB (IG+insulin aspart ≤4 times/day; n=254). IDegLira was initiated at 16U (16U insulin degludec + 0.58 mg liraglutide); initial IG dose was the pre-trial dose (mean 33U). Both were titrated twice weekly, based on the mean of 3 pre-breakfast self-monitored plasma glucose measurements (SMPG, target 4–5 mmol/L). Insulin aspart, initiated at 4U/main meal, was titrated twice weekly to a pre-prandial and bedtime SMPG (target 4–6 mmol/L). Despite the lower starting basal insulin dose with IDegLira vs. BB, the number of basal insulin dose adjustments was similar during treatment (16.6 and 17.1, respectively). The number of bolus adjustments during treatment increased steadily to a median of 218/patient (min=1; max=569). At Week 26, 66.5% of patients in the BB group were receiving ≥3 bolus injections/day in addition to IG and took SMPG measurements at each injection. Compared with BB, the clinical benefits of IDegLira (comparable A1C reduction, weight loss and significantly lower hypoglycemia rates ) were achieved with fewer daily injections, SMPG readings and dose adjustments in DUAL VII.

Self-Managed Titration with Insulin Glargine 300 U/mL (Gla-300) Can Achieve Similar Efficacy to Physician-Led Titration Regardless of Prior Insulin Status in People with T2DM—Results from TAKE CONTROL

Many people with T2DM do not achieve HbA1c goals in clinical practice, owing in part to sub-optimal basal insulin titration. TAKE CONTROL, a 24-week, multicenter, randomized, open-label, parallel-group study, compared the efficacy and safety of a Gla-300 titration algorithm (fasting self-monitored plasma glucose &amp;gt;130 mg/dL, +3 U; &amp;lt;80 mg/dL, −3 U), when self-managed or led by physicians. Overall, improved glycemic control without increased hypoglycemia was seen with self-titration. Here, we report results stratified by prior insulin use. At baseline, mean HbA1c was higher in the insulin-naïve vs. prior-insulin group (Table). In both groups, self-titration and physician-led titration resulted in similar HbA1c reduction. For confirmed or severe hypoglycemia, there was no evidence of heterogeneity between titration approaches for both glycemic thresholds (≤70 mg/dL or &amp;lt;54 mg/dL). Glycemic goal achievement with Gla-300 using self-titration was similar to that reported for physician-led titration, regardless of prior insulin use, but with reduced or similar risk of hypoglycemia. Empowering people with T2DM to self-titrate their basal insulin effectively upon Gla-300 initiation, or after switching to Gla-300, can improve glycemic target achievement without increasing hypoglycemia. Disclosure 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. M. Bonnemaire: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. A. Dauchy: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. V. Donicova: None. M. Kvapil: None. N. Tentolouris: Advisory Panel; Self; MSD K.K., AstraZeneca, Sanofi, Novo Nordisk A/S, Elpen Pharmaceutical Co. Inc., Eli Lilly and Company, Boehringer Ingelheim GmbH, Novartis AG. Research Support; Self; MSD K.K., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Pfizer Inc., AstraZeneca, Janssen-Cilag Pty Limited, GlaxoSmithKline plc., Novartis AG. L. Popescu: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. D. Russell-Jones: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim, Cellnovo, Eli Lilly and Company, Novartis, Novo Nordisk, Sanofi.

Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

IntroductionAlthough reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported.MethodsForty patients with type 2 diabetes who were admitted for glycemic control with basal–bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100–120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge.ResultsIn the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033).ConclusionIn type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100.Trial RegistrationUMIN clinical trials registry (UMIN000023360).