Hypoglycemia Outcomes Research Articles

Real-world outcomes of treatment with insulin glargine 300 U/mL versus standard-of-care in people with uncontrolled type 2 diabetes mellitus

Objective To compare real-world outcomes with newer (insulin glargine 300 U/mL; Gla-300) versus standard of care (SoC) basal insulins (BIs) in the REACH (insulin-naïve; NCT02967224) and REGAIN (basal insulin-treated; NCT02967211) studies in participants with uncontrolled type 2 diabetes (T2DM) in Europe and Brazil. Methods In these open-label, parallel-group, pragmatic studies, patients (HbA1c > 7.0%) were randomized to Gla-300 or SoC BI for a 6-month treatment period (to demonstrate non-inferiority of Gla-300 vs SoC BIs for HbA1c change [non-inferiority margin 0.3%]) and a 6-month extension period (continuing with their assigned treatment). Insulin titration/other medication changes were at investigator/patient discretion post-randomization. Results Overall, 703 patients were randomized to treatment in REACH (Gla-300, n = 352; SoC, n = 351) and 609 (Gla-300, n = 305, SoC, n = 304) in REGAIN. The primary outcome, non-inferiority of Gla-300 versus SoC for HbA1c change from baseline to month 6, was met in REACH (least squares [LS] mean difference 0.12% [95% CI –0.046 to 0.281]) but not REGAIN (LS mean difference 0.17% [0.015–0.329]); no between-treatment difference in HbA1c change was shown after 12 months in either study. BI dose increased minimally from baseline to 12 months in REACH (Gla-300, +0.17 U/kg; SoC, +0.15 U/kg) and REGAIN (Gla-300, +0.11 U/kg; SoC, +0.07 U/kg). Hypoglycemia incidence was low and similar between treatment arms in both studies. Conclusions In both REACH and REGAIN, no differences in glycemic control or hypoglycemia outcomes with Gla-300 versus SoC BIs were seen over 12 months. However, the suboptimal insulin titration in REACH and REGAIN limits comparisons of outcomes between treatment arms and suggests that more titration instruction/support may be required for patients to fully derive the benefits from newer basal insulin formulations.

Diabetes Education Impact on Hypoglycemia Outcomes: A Systematic Review of Evidence and Gaps in the Literature.

The primary purpose of this study is to report a systematic review of evidence and gaps in the literature among well-conducted studies assessing the impact of diabetes education on hypoglycemia outcomes and secondarily reporting the impact on other included target outcomes. The authors used a modified Cochrane method to systematically search and review English-language titles, abstracts, and full-text articles published in the United States between January 2001 and December 2017, with diabetes education specified as an intervention and a directly measurable outcome for hypoglycemia risk or events included. Fourteen quasi-experimental, experimental, and case-control studies met the inclusion criteria, with 8 articles reporting a positive impact of diabetes self-management education and support (DSMES) on hypoglycemia outcomes; 2 of the 8 reported decreased hypoglycemia events, and 1 reported decreased events in both the intervention and control groups. In addition, 5 studies targeted change in reported hypoglycemia symptoms, with all 5 reporting a significant decrease. DSMES also demonstrated an impact on intermediate (knowledge gain, behavior change) and long-term (humanistic and economic/utilization) outcomes. An absence of common hypoglycemia measures and terminology and suboptimal descriptions of DSMES programs for content, delivery, duration, practitioner types, and participants were identified as gaps in the literature. Most retained studies reported that diabetes education positively affected varied measures of hypoglycemia outcomes (number of events, reported symptoms) as well as other targeted outcomes. Diabetes education is an important intervention for reducing hypoglycemia events and/or symptoms and should be included as a component of future hypoglycemia risk mitigation studies.

Long-Term Effectiveness of Continuous Subcutaneous Insulin Infusion in the Prevention of Hypoglycemia in Adults with Type 1 Diabetes

Background: Reducing hyperglycemia while avoiding hypoglycemia is the key clinical goal in managing people with type 1 diabetes. Insulin delivery techniques and regimens are constantly evolving to achieve these goals. At present, use of multiple daily injections (MDI) is the standard of care, but there is increasing interest in continuous subcutaneous insulin infusion (CSII). There is a deficit of studies comparing long-term glycemic control and hypoglycemia outcomes between these therapeutic options. Methods: This was a single-center, retrospective cohort study of adults with type 1 diabetes. Data were derived from electronic medical records and included demographic and clinical factors. Participants had all undergone intensive diabetes education, followed by CSII or continued MDI. The primary outcome was difference in hypoglycemia, defined as the percentage of self-monitoring blood glucose levels less than 3.9 mmol/L. Up to 10 years of follow-up data were available, between 2000 and 2016. Results: There were 69 participants using CSII and 78 using MDI. Self-monitoring blood glucose data showed significantly less hypoglycemia with CSII by over 30%, occurring as early as the first year and sustained throughout the follow-up period (P < 0.001). This benefit of CSII on reducing hypoglycemia was independent of more frequent hypoglycemia and higher body weight at baseline, factors that were also independently associated with reduced hypoglycemia. Conclusions: In selected adults with type 1 diabetes, long-term CSII can provide long-term clinically relevant and sustained reductions in hypoglycemia, particularly in those with greater initial risk of hypoglycemia and higher body weight, and improved glycemic control compared with MDI.

120-LB: Early Real-World Hypoglycemia Outcomes with Use of the Tandem Basal-IQ Technology System

The Tandem t:slim X2™ insulin pump with Basal-IQ® technology predicts glucose levels 30 minutes ahead based on the last 4 consecutive CGM readings. Insulin delivery is suspended if the predicted sensor glucose (SG) is &amp;lt;80 mg/dL or if the observed SG is &amp;lt;70 mg/dL. Insulin delivery resumes as soon as SG begins to rise. The pivotal trial (PROLOG) showed 3 weeks of Basal-IQ® use reduced SG time &amp;lt;70 mg/dL by 31% compared to sensor-augmented pump. De-identified data voluntarily uploaded to the t:connect® diabetes management application between August 30, 2018, and February 7, 2019, from individuals with diabetes who have used Basal-IQ® technology for 3, 6, and 9 weeks (N=4082, 2370, and 1307 respectively) were retrospectively analyzed. Real-world Basal-IQ® hypoglycemia outcomes were compared to the PROLOG results. After 3 weeks of real-world use, median time SG &amp;lt;70 mg/dL was 1.0% overall (1.0% daytime and 0.9% nighttime) vs. 2.6% (2.4% daytime and 2.7% nighttime) in PROLOG. Median time with SG &amp;lt;60 was 0.3% and time &amp;lt;50 mg/dL was 0.1%, vs. 0.9% and 0.2% in PROLOG. After 6 and 9 weeks, median time SG &amp;lt;70 mg/dL was 1.1%. Number of insulin suspensions and suspension duration were similar to PROLOG (Table 1). Basal-IQ® technology was found to be safe and effective in a real-world setting, with similar PLGS activation metrics as observed in PROLOG. Results showed the Basal-IQ® algorithm performs successfully at preventing hypoglycemia. Disclosure J.E. Pinsker: Research Support; Self; Ascensia Diabetes Care, Dexcom, Inc., Insulet Corporation, LifeScan, Inc., Roche Diabetes Care, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. K.N. Castorino: Consultant; Self; Abbott. Research Support; Self; Abbott, Dexcom, Inc., Drawbridge, Novo Nordisk Inc., Sanofi US. S.A. Leas: Employee; Self; Tandem Diabetes Care. S. Habif: Employee; Self; Tandem Diabetes Care. Funding Tandem Diabetes Care, Inc.

395-P: Hypoglycemia and Cardiovascular Outcomes among Older Adults: The Atherosclerosis Risk in Communities Study

Background: There is limited community-based data on the association of hypoglycemia with cardiovascular events among older individuals, who are particularly susceptible to hypoglycemia. Methods: We conducted a prospective cohort analysis of adults with diabetes aged ≥70 years from the Atherosclerosis Risk in Communities (ARIC) Study (baseline visit 5, 2011-2013). History of severe hypoglycemia was defined using first position ICD-9 codes from prior hospitalizations, emergency department visits, and ambulance calls through June 1, 2011. We evaluated the rate of cardiovascular events (myocardial infarction, fatal coronary heart disease, stroke or heart failure) and mortality (follow-up through December 31, 2017), using negative binomial and Cox proportional hazards regression models. Results: Among 2,194 participants with diabetes (mean age: 75 years [SD: 5], 57% female, 32% blacks), 79 had a history of severe hypoglycemia. During a median follow-up of 5.4 years, a history of severe hypoglycemia was strongly associated with cardiovascular disease (incident and recurrent) and death (Table). Conclusions: Our findings suggest potential cardiovascular benefits of severe hypoglycemia prevention among older individuals and provide strong evidence for relaxing the targets of blood glucose control among older individuals. Disclosure J.B. Echouffo Tcheugui: None. N.R. Daya: None. O. Tang: None. B. Windham: None. A. Shah: Advisory Panel; Self; Philips Ultrasound. Consultant; Self; Bellerophon. Other Relationship; Self; Novartis Pharmaceuticals Corporation. E. Selvin: None.

402-P: Higher Glucose Thresholds for Hypoglycemia Alarms on Continuous Glucose Monitoring Systems Correlate with Less Time in Hypoglycemia

Based on the set glucose thresholds for hypoglycemia alarms, continuous glucose monitoring (CGM) systems can provide audible alerts that notify individuals for actual/impending hypoglycemic events. While CGMs have been shown to reduce hypoglycemic events in patients with type 1 diabetes (T1D), there are little data demonstrating the association between glucose thresholds for hypoglycemia alarms and clinical hypoglycemia outcomes. This cross-sectional observational study enrolled 83 T1D patients with CGM use &amp;gt;3 months, active CGM usage time ≥70% and activated (i.e., turned “on”) hypoglycemia alarms. CGM settings and two-week CGM glucose data (total 25,683 hours) were analyzed. Glucose thresholds for hypoglycemia alarms (mean: 74 ± 8 mg/dL; range: 60-100 mg/dL) correlated inversely with time in hypoglycemia (both glucose &amp;lt;54 and &amp;lt;70 mg/dL) (Figure 1a). When comparing the cohort with hypoglycemia alarm threshold settings at glucose level ≤70 mg/dL (n=42), threshold settings ≥75 mg/dL (n=41) were associated with a 74% and 60% reduction in hypoglycemia time (&amp;lt;54 and &amp;lt;70 mg/dL, respectively) (Figure 1b). All subjects with hypoglycemia alarm set at glucose ≥75 mg/dL spent less than 3% of time with glucose &amp;lt;54 mg/dL. The current data support the use of higher glucose thresholds on CGM hypoglycemia alarms to decrease the time in hypoglycemia in patients with T1D. Disclosure Y. Lin: None. M. Hung: None. A. Sharma: None. O. Chan: Research Support; Self; Zucara Therapeutics Inc. M. Varner: None. D. Groat: None. D. Dopita: None. S. Fisher: None.

Glycaemic goal attainment and hypoglycaemia outcomes in type 2 diabetes patients initiating insulin glargine 300 units/mL or 100 units/mL: Real-world results from the DELIVER Naïve cohort study.

AimsTo compare HbA1c and hypoglycaemia in insulin‐naïve patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla‐300) or 100 units/mL (Gla‐100).Materials and methodsThis retrospective cohort study examined electronic medical records of insulin‐naïve adults with T2D who initiated Gla‐300 or Gla‐100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6‐month baseline and 90–180‐day follow‐up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score‐matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria.ResultsThe matched cohorts included 1004 Gla‐300 and 2008 Gla‐100 initiators (mean age 60.4 years; 53.2% male). During 6‐month follow‐up, Gla‐300 versus Gla‐100 initiators had a greater mean HbA1c decrease (−1.52 ± 2.08% vs. –1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c <7% (25.0% vs. 21.5%; P = 0.029) and <8% (55.0% vs. 49.2%; P = 0.002); and HbA1c <7% (21.9% vs. 17.4%; P = 0.003) and <8% (49.1% vs. 41.8%; P < 0.001) without hypoglycaemia. Gla‐300 initiators were similarly or less likely to have any or inpatient/emergency department‐associated hypoglycaemia during 3‐ and 6‐month follow‐up (e.g. any hypoglycaemia to 6 months: 9.7% vs. 12.5%; adjusted odds ratio 0.61; P = 0.057).ConclusionsAmong insulin‐naïve adults with T2D, Gla‐300 was associated with significantly better HbA1c reductions (latest value during 90–180‐day follow‐up) and similar or improved hypoglycaemia outcomes (3‐ and 6‐month follow‐up) than Gla‐100.

Sweet and Sour: Impact of Early Glycemic Control on Outcomes in Necrotizing Soft-Tissue Infections.

Background: Necrotizing soft-tissue infection (NSTI) is a devastating disease associated with high rates of morbidity and mortality. Hyperglycemia is associated with poor wound healing; however, there are no studies evaluating glycemic control outcomes in patients with NSTI. The objective of this study was to examine disease progression and death in patients with NSTI who achieved early glycemic control (EGC) compared with patients that did not. Methods: A retrospective chart review of patients with NSTI was conducted between November 2011 and August 2017. Early glycemic control was defined as a daily average blood glucose concentration ≤150 mg/dL for a minimum of two consecutive days from admission to hospital day three. The primary outcome of this study was a composite of ≤3 debridement procedures by hospital day 14 and survival to discharge. Secondary outcomes were the total number of debridement procedures, amputation, hospital length of stay (LOS), intensive care unit (ICU) LOS, number of hypoglycemic events throughout hospitalization, and discharge disposition. Results: One-hundred five patients were included in the analysis. There were 62% male patients, mean age of 55.3 years, mean weight of 106.9 kg, and 57.1% with diabetes mellitus (DM). The 54 (51.4%) patients with EGC were less likely to have DM (29.6% versus 86.3%; p < 0.001), had a lower median admission glucose concentration (120.5 [97-144] versus 198 [153-295.5] mg/dL; p < 0.001), and had lower median daily glucose values during the first 96 hours after admission (p < 0.001). There was no significant difference in the primary outcome (83.3%% versus 84.3%; p > 0.99) or incidence of hypoglycemia (14.8% versus 23.5%; p = 0.32). Patients with EGC were more likely to return home after discharge (44.4% versus 23.5%; p = 0.039). Conclusion: Overall, there was no difference in composite clinical outcomes between patients with EGC and those without, although more patients who achieved EGC were discharged home. Patients with DM were less likely to achieve EGC.

Prevalence and outcome of hypoglycemia in children attending emergency pediatric unit of a specialist hospital in Nigeria

Background: Hypoglycemia is a common metabolic problem encountered in pediatric emergency admissions. The absence of clinical symptoms does not preclude the presence of hypoglycemia as presentation may vary from asymptomatic to central nervous system and cardiopulmonary disturbances. If untreated, hypoglycemia can result in permanent neurological damage or even death. Objectives: The objective of the study is to determine the prevalence, associated factors and outcome of hypoglycemia in pediatric emergency admissions at Ahmad Sani Yariman Bakura Specialist Hospital, Gusau, Nigeria. Materials and Methods: The study was a prospective cross-sectional study involving children aged 1 month–13 years. Blood glucose was determined at admission using Accu-Chek® Active Blood Glucose Meter, and hypoglycemia was defined as blood glucose levels

538: Outcomes of elective induction of labor at 39 weeks versus expectant management until week 40

This study analyzes differences in maternal and neonatal outcomes from elective induction of labor (eIOL) at 39 weeks versus one additional week of expectant management in nulliparous women at community hospitals. We conducted a retrospective cohort study of singleton, vertex, nonanomalous deliveries in community hospitals in California between 2007 and 2011 using linked hospital discharge and vital statistics data (n=252,107). We compared outcomes from eIOL, defined by the Joint Commission, at 39 weeks against one additional week of expectant management and delivery at 40 weeks. The maternal outcomes of interest were cesarean delivery, operative vaginal delivery, maternal blood transfusion, perineal tear, chorioamnionitis, and endomyometritis. Neonatal outcomes of interest were intrauterine fetal death, 5 minute Apgar less than 7, NICU admission, respiratory distress syndrome (RDS), hypoglycemia, hypoxic ischemic encephalopathy (HIE) and jaundice. Results were compared using chi square analysis and examined using multivariate logistic regression controlling for maternal age, comorbidities, ethnicity, education level, initiation of prenatal care in the first trimester, and insurance status. A p-value of less than 0.05 was used to indicate statistical significance. In our cohort of 252,107 deliveries, there were significant differences in the incidence of cesarean delivery, operative vaginal delivery, maternal transfusion, perineal tear, chorioamnionitis, endomyometritis in women who were electively induced at 39 weeks compared to those who received expectant management and delivered at 40 weeks. Rates of adverse neonatal outcomes of intrauterine fetal death and hypoglycemia were also significantly decreased when women were electively induced at 39 weeks. However, RDS, HIE and jaundice were not significantly different between the two groups. Logistic regression analysis indicated expectant management until 40 weeks significantly increased cesarean deliveries (OR 1.37, 95% CI 1.32-1.42) and operative vaginal deliveries (OR 1.0, 95% CI 1.02-1.15). The maternal and neonatal outcomes following birth are associated with the timing and management prior to delivery. These findings can be used to counsel women regarding the risks of maternal and neonatal complications from elective induction of labor and one additional week of expectant management.

691: Outcomes of elective induction of labor at 38 weeks versus expectant management until week 39

Recent evidence suggests that elective induction of labor may reduce cesarean deliveries and other obstetric outcomes. This study analyzes differences in maternal and neonatal outcomes from elective induction of labor (eIOL) at 38 weeks versus one additional week of expectant management in nulliparous women at community hospitals. We conducted a retrospective cohort study of singleton, vertex, nonanomalous deliveries in community hospitals in California between 2007 and 2011 using linked hospital discharge and vital statistics data (n=231,567). We compared outcomes from eIOL, defined by the Joint Commission, at 38 weeks against one additional week of expectant management and delivery at 39 weeks. Maternal outcomes of interest were cesarean delivery, operative vaginal delivery, perineal tear, chorioamnionitis, and endomyometritis. Neonatal outcomes of interest were intrauterine fetal death, 5 minute Apgar less than 7, NICU admission, respiratory distress syndrome (RDS), hypoglycemia, hypoxic ischemic encephalopathy (HIE) and jaundice. Results were compared using chi square analysis and examined using multivariate logistic regression. A p-value of less than 0.05 was used to indicate statistical significance. In our cohort of 231,567 deliveries, there were significant differences in the incidence of cesarean delivery, perineal tears, chorioamnionitis, and endomyometritis in women who were electively induced at 38 weeks compared to those who received expectant management and delivered at 39 weeks. However, the rate of operative vaginal delivery was not significantly different between the two groups. The rate of intrauterine fetal death was also significantly decreased when women were electively induced at 38 weeks. Logistic regression analysis indicated expectant management for one additional week, with delivery at 39 weeks, significantly increased cesarean deliveries (OR 1.45, 95% CI 1.37-1.54) but decreased RDS in neonates (OR 0.83, 95% CI 0.71- 0.98). There were no differences between the two groups for neonatal outcomes of hypoglycemia, HIE and jaundice. The maternal and neonatal outcomes following birth are associated with the timing and management prior to delivery. These findings can be used to counsel women regarding the risks of maternal and neonatal complications from elective induction of labor and expectant management for one additional week.

Clinical characteristics and outcomes of symptomatic and asymptomatic hypoglycemia in hospitalized patients with diabetes

ImportanceThe frequency and impact of asymptomatic hypoglycemia in hospitalized patients with diabetes is not known.ObjectiveWe determined the clinical characteristics and hospital outcomes of general medicine and surgery patients with symptomatic...

Systematic review of incretin therapy during peri-operative and intensive care

BackgroundGlucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are incretin hormones. By lowering blood glucose in a glucose-dependent manner, incretin-based therapies represent a novel and promising intervention to treat hyperglycaemia in hospital settings. We performed a systematic review of the literature for all current applications of incretin-based therapies in the peri-operative and critical care settings.MethodsWe searched MEDLINE, the Cochrane Library, and Embase databases for all randomised controlled trials using exogenous GLP-1, GLP-1 receptor agonists, exogenous GIP and dipeptidyl peptidase IV inhibitors in the setting of adult peri-operative care or intensive care. We defined no comparator treatment. Outcomes of interest included blood glucose, frequency of hypoglycaemia and insulin administration.ResultsOf the 1190 articles identified during the initial literature search, 38 fulfilled criteria for full-text review, and 19 single-centre studies were subsequently included in the qualitative review. Of the 18 studies reporting glycaemic control, improvement was reported in 15, defined as lower glucose concentrations in 12 and as reduced insulin administration (with similar glucose concentrations) in 3. Owing to heterogeneity, meta-analysis was possible only for the outcome of hypoglycaemia. This revealed an incidence of 7.4% in those receiving incretin-based therapies and 6.8% in comparator groups (P = 0.94).ConclusionsIn small, single-centre studies, incretin-based therapies lowered blood glucose and reduced insulin administration without increasing the incidence of hypoglycaemia.Trial registrationPROSPERO, CRD42017071926.

Switching from Flash Glucose Monitoring to Continuous Glucose Monitoring on Hypoglycemia in Adults with Type 1 Diabetes at High Hypoglycemia Risk: The Extension Phase of the I HART CGM Study.

Background: The I HART CGM study showed that real-time continuous glucose monitoring (RT-CGM) has greater beneficial impact on hypoglycemia than intermittent flash glucose monitoring (flash) in adults with type 1 diabetes (T1D) at high risk. The impact of continuing RT-CGM or switching from flash to RT-CGM for another 8 weeks was then evaluated.Methods: Prospective randomized parallel group study with an extension phase. After a 2-week run-in with blinded CGM, participants were randomized to either RT-CGM or flash for 8 weeks. All participants were then given the option to continue with RT-CGM for another 8 weeks. Glycemic outcomes at 8 weeks are compared with the 16-week endpoint.Results: Forty adults with T1D on intensified multiple daily insulin injections and with impaired awareness of hypoglycemia or a recent episode of severe hypoglycemia were included (40% female, median [IQR] age 49.5 [37.5–63.5] years, diabetes duration 30.0 [21.0–36.5] years, HbA1c 56 [48–63] mmol/mol, and Gold Score 5 [4–5]), of whom 36 completed the final 16-week extension. There was a significant reduction in percentage time in hypoglycemia (<3.0 mmol/L) in the group switching from flash to RT-CGM (from 5.0 [3.7–8.6]% to 0.8 [0.4–1.9]%, P = 0.0001), whereas no change was observed in the RT-CGM group continuing with the additional 8 weeks of RT-CGM (1.3 [0.4–2.8] vs. 1.3 [0.8–2.5], P = 0.82). Time in target (3.9–10 mmol/L) increased in the flash group after switching to RT-CGM (60.0 [54.5–67.8] vs. 67.4 [56.3–72.4], P = 0.02) and remained the same in the RT-CGM group that continued with RT-CGM (65.9 [54.1–74.8] vs. 64.9 [49.2–73.9], P = 0.64).Conclusions: Our data suggest that switching from flash to RT-CGM has a significant beneficial impact on hypoglycemia outcomes and that continued use of RT-CGM maintains hypoglycemia risk benefit in this high-risk population.

Impact of Background Antihyperglycemic Therapy on Insulin Glargine 300 U/mL (Gla-300) vs. Insulin Degludec 100 U/mL (IDeg-100) in Insulin-Naïve People with T2DM from the BRIGHT Randomized Study

BRIGHT (NCT02738151), the first head-to-head trial of Gla-300 and IDeg-100 in T2DM, is a multicenter, open-label, randomized, parallel-group, 24-week actively controlled study, conducted in insulin-naïve participants uncontrolled on current antihyperglycemic drugs. Participants (mean baseline HbA1c 8.6%, diabetes duration 10.6 years, BMI 31.5 kg/m2) received Gla-300 (N=466) or IDeg-100 (N=463), titrated to a fasting SMPG of 80-100 mg/dL, and remained on metformin ± previous antihyperglycemic therapy. Primary endpoint: change in HbA1c from baseline to week 24; safety endpoints included hypoglycemia incidence. Here we report HbA1c and hypoglycemia outcomes by background antihyperglycemic therapy (no comparisons were performed for metformin as it was received by 92% of participants). Overall distribution of background therapy was: SU/Glinides (65.7%/2.3%), DPP-4i (24.4%), SGLT2i (13.3%), GLP-1 RA (11.9%). No evidence of heterogeneity of treatment effect according to use of background antihyperglycemic therapy on HbA1c reductions (Table), or incidence of confirmed (≤70 mg/dL or &amp;lt;54 mg/dL) or severe hypoglycemia was shown (all p&amp;gt;0.05). In conclusion, background antihyperglycemic therapies had no impact on the comparable efficacy and hypoglycemia profiles of Gla-300 and IDeg-100. Disclosure R. Roussel: Advisory Panel; Self; AbbVie Inc., Abbott, Eli Lilly and Company, Sanofi, Novo Nordisk A/S, AstraZeneca. Speaker's Bureau; Self; Servier. Consultant; Self; Bayer AG. Advisory Panel; Self; Merck Sharp &amp; Dohme Corp.. Research Support; Self; Amgen Inc., Sanofi, Novo Nordisk A/S, Danone Research. Stock/Shareholder; Self; Iriade. Advisory Panel; Self; Physiogenex S.A.S. J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck &amp; Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. J. Pettus: Advisory Panel; Self; Sanofi, Novo Nordisk Inc.. Consultant; Self; MannKind Corporation. Advisory Panel; Self; Insulet Corporation. Consultant; Self; Senseonics. R. Ritzel: Speaker's Bureau; Self; AstraZeneca. Consultant; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Consultant; Self; Servier. Speaker's Bureau; Self; Bristol-Myers Squibb Company, Merck Sharp &amp; Dohme Corp., Boehringer Ingelheim GmbH, Eli Lilly and Company, Novartis Pharmaceuticals Corporation. A. Cheng: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Merck &amp; Co., Inc.. Speaker's Bureau; Self; Merck &amp; Co., Inc.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Consultant; Self; Takeda Canada Inc.. Research Support; Self; Sanofi, Boehringer Ingelheim GmbH. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. C. Devisme: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. A.M. Cali: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. X. Wang: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. G.B. Bolli: Speaker's Bureau; Self; Menarini Group, Sanofi. Research Support; Self; Sanofi.

Self-Titration with Insulin Glargine 300 or 100 U/mL has Improved Efficacy vs. Physician-Led Titration—Comparison of the TAKE-CONTROL, AT.LANTUS, and ATLAS Studies in People with Type 2 Diabetes (T2DM)

Empowering individuals to self-titrate their basal insulin may help to reduce rates of sub-optimal titration often observed in clinical practice and help more people achieve HbA1c goals. Here we compare the results from the recently completed TAKE CONTROL study, which evaluated self-titration and physician-led titration of insulin glargine 300 U/mL (Gla-300) in people with T2DM, with comparable studies (AT.LANTUS and ATLAS) of insulin glargine 100 U/mL (Gla-100). All 3 studies were 24-week, multicenter, randomized, open-label, parallel-group studies. Fasting blood glucose targets were 80-130 mg/dL (4.4-7.2 mmol/L) in TAKE CONTROL, ≤100 mg/dL (5.5 mmol/L) in AT.LANTUS and ≤110 mg/dL (6.1 mmol/L) in ATLAS. Mean baseline HbA1c was between 8.4 and 8.9% (Table). Self-titration statistically significantly lowered mean HbA1c by 0.97 to 1.40% vs. physician-led titration (0.84 to 1.25%; p&amp;lt;0.for all 3 studies). The incidence of severe hypoglycemia and other safety outcomes was similar between titration arms in all 3 studies (Table). Both Gla-300 and Gla-100 were effective in improving glycemic control. Self-titration with Gla-300 resulted in significantly improved glycemic control vs. physician-led titration, as demonstrated previously with Gla-100, without increased hypoglycemia. Disclosure M. Davies: Advisory Panel; Self; AstraZeneca. Board Member; Self; AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Board Member; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Board Member; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Board Member; Self; Sanofi-Aventis. Consultant; Self; Sanofi-Aventis. Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Advisory Panel; Self; Servier. Consultant; Self; Intarcia Therapeutics, Inc.. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. E. Boelle-Le Corfec: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. M. Odawara: Speaker's Bureau; Self; Sanofi, Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Eli Lilly and Company. Advisory Panel; Self; Sanofi, Novo Nordisk Inc., Eli Lilly and Company. L. Popescu: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Sieber: 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. K. Strojek: Research Support; Self; AstraZeneca. Other Relationship; Self; Sanofi-Aventis, Novo Nordisk A/S. Speaker's Bureau; Self; Servier, Eli Lilly and Company, MSD K.K., Boehringer Ingelheim GmbH. Research Support; Self; Pfizer Inc., Amgen Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc. 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.

The Use of Supportive Tools and Education Enables Self-Titration with Insulin Glargine 300 (Gla-300) or 100 U/mL (Gla-100) in People with Type 2 Diabetes (T2DM)—Results from TAKE CONTROL, INNOVATE, and AUTOMATIX

Supporting people with T2DM with education and titration tools may empower them to optimize basal insulin self-titration in order to reach glycemic targets. Three multicenter, randomized, open-label, parallel-group studies have investigated self-titration (supported by either a paper algorithm, web tool or device) vs. physician-led titration in people with T2DM, switching to or initiating Gla-300 (TAKE CONTROL and AUTOMATIX) or Gla-100 (INNOVATE). Fasting blood glucose targets for self-titration were 80-130 mg/dL (4.4-7.2 mmol/L) in TAKE CONTROL and 90-130 mg/dL (5.0-7.2 mmol/L) in both INNOVATE and AUTOMATIX. Self-titration resulted in greater or similar mean HbA1c reductions from baseline vs. physician-led titration (Table). By using self-titration with Gla-300, more people with T2DM achieved fasting glucose targets without confirmed or severe hypoglycemia vs. physician-led titration (TAKE CONTROL and AUTOMATIX). Severe hypoglycemia and other safety outcomes were similar between titration arms in all 3 studies. Self-titration with Gla-300 and Gla-100 using either a paper or device-based algorithm resulted in improved or similar reductions in HbA1c, without an increased risk of hypoglycemia or safety concerns. Disclosure M. Kvapil: None. M. Bonnemaire: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. H. Goyeau: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. N. Papanas: None. L. Popescu: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. B. Schultes: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, AstraZeneca, Eli Lilly and Company, Bayer AG, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Sanofi, Eli Lilly and Company, MSD K.K., Bayer AG, Boehringer Ingelheim GmbH. J. Sieber: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Duvnjak: None.

More patients reach glycaemic control with a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) than with basal insulin at 12 weeks of treatment: A post hoc time-to-control analysis of LixiLan-O and LixiLan-L.

The present post hoc analysis of two 30‐week clinical trials compared efficacy and hypoglycaemia outcomes at early study visits with iGlarLixi (insulin glargine U100 [iGlar] and lixisenatide) vs iGlar alone in patients with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs; LixiLan‐O trial) or basal insulin (LixiLan‐L trial). Time to control, defined as days to achieve glycated haemoglobin (HbA1c) <53 mmol/mol (<7%) or fasting plasma glucose (FPG) ≤7.2 mmol/L, was estimated using the Kaplan–Meier method. In the LixiLan‐O and LixiLan‐L trials, 60% and 46% of patients, respectively, reached HbA1c <53 mmol/mol (<7%) with iGlarLixi at 12 weeks, vs 45% and 24%, respectively, with iGlar. In the LixiLan‐O trial, the median time to target HbA1c was approximately half with iGlarLixi vs iGlar (85.0 vs 166.0 days; P < .0001). In the LixiLan‐L trial, the median time to target HbA1c was 153.0 days with iGlarLixi, while target HbA1c was never reached by 50% of patients with iGlar (P < .0001). Time‐to‐target FPG and hypoglycaemia outcomes were similar between treatments. In T2D uncontrolled on OADs or basal insulin, iGlarLixi resulted in glycaemic control in more patients than did iGlar at early treatment time points.

Mismatch between GLUTs and glucose levels causes neuronal damage during glucose fluctuations

Abnormal glucose levels damage the central nervous system, especially in case of rapid fluctuations. Even a single episode of glucose reperfusion can result in overt impairment of neurons. Oxidative stress plays an important role in this process, sharing properties with the pathophysiologic changes of glucose neurotoxicity. Glucose transporters (GLUTs) located in the brain are involved in direct glucose uptake by neurons. Instead of being insulin-sensitive, these transporters are regulated by glucose levels in the extracellular fluid, increasing their expression while glucose levels fall, to absorb more glucose. Therefore, we hypothesized that mismatch between altered GLUTs and sudden glucose level changes is responsible for neuronal damage during glucose fluctuations. Modulating hypoglycemia by increasing blood glucose slowly may improve the neurological outcomes of hypoglycemia.

Impact of late pregnancy haemoglobin A1c at 29–30 weeks’ gestation on adverse pregnancy outcomes among women with pre-existing diabetes: a retrospective analysis

This study was to assess the relationship between late pregnancy haemoglobin A1C (HbA1C) at 29–30 weeks of gestation and adverse pregnancy outcomes (APOs) in 272 pregnant women with pre-existing diabetes. HbA1C ≥6.1% was associated with significantly increased risk of preterm delivery, Caesarean section, large for gestational age (LGA), neonatal respiratory distress, neonatal hypoglycaemia, and composite adverse neonatal outcome (p < .05). The risk of pre-eclampsia increased significantly at the lower HbA1C cut-off of > 5.6% (p = .039). Reduction of HbA1C cut-off from 6.1% to 5.6% improved the sensitivity but reduced the specificity for prediction of APOs. Overall, the receiver operating characteristic (ROC) curves demonstrated the moderate predictive value of late pregnancy HbA1C for APOs. In conclusion, elevated late pregnancy HbA1C levels at 29–30 gestational weeks had a negative impact on APOs in pregnant women with pre-existing diabetes. However, HbA1C cut-off levels of neither ≥6.1% nor >5.6% were ideal for predicting APOs.Impact statementWhat is already known on this subject: Poorly controlled diabetes is associated with adverse pregnancy outcomes (APOs). Periconceptual haemoglobin A1C (HbA1C) correlates well with the risk of foetal anomaly but is not predictive of APOs at time of delivery. New evidence suggested that late pregnancy HbA1C is predictive of APOs but the definitions of a late pregnancy gestational week and target HbA1C cutpoint remain in doubt.What the results of this study add: This study investigated the relationship between late pregnancy HbA1C levels at 29–30 weeks of gestation and the APOs among pregnant women with pre-existing diabetes. Late pregnancy HbA1C ≥ 6.1% correlated with the risk of APOs but the increased risk of pre-eclampsia only became significant at the lower cut-off of >5.6%. Reducing HbA1C cut-off from 6.1% to 5.6% improved the sensitivity but reduced the specificity for prediction of APOs. Overall, late pregnancy HbA1C had a moderate predictive value for APOs.What the implications are of these findings for clinical practice and/or further research: HbA1C cut-off levels of neither ≥6.1% nor >5.6% were ideal in predicting APOs among pregnant women with pre-existing diabetes. As HbA1C levels tend to drop in pregnancy, caution should be taken when interpreting HbA1C in pregnancy. More multi-centred studies are required to explore the respective glycaemic target for each APO and to determine the ideal timing for late pregnancy HbA1C measurement.