Randomized Clinical Trial Comparing Basal Insulin Peglispro and Insulin Glargine in Patients With Type 2 Diabetes Previously Treated With Basal Insulin: IMAGINE 5

OBJECTIVE To evaluate the efficacy and safety of basal insulin peglispro (BIL) versus insulin glargine in patients with type 2 diabetes (hemoglobin A1c [HbA1c] ≤9% [75 mmol/mol]) treated with basal insulin alone or with three or fewer oral antihyperglycemic medications. RESEARCH DESIGN AND METHODS This 52-week, open-label, treat-to-target study randomized patients (mean HbA1c 7.42% [57.6 mmol/mol]) to BIL ( n = 307) or glargine ( n = 159). The primary end point was change from baseline HbA1c to 26 weeks (0.4% [4.4 mmol/mol] noninferiority margin). RESULTS At 26 weeks, reduction in HbA1c was superior with BIL versus glargine (−0.82% [−8.9 mmol/mol] vs. −0.29% [−3.2 mmol/mol]; least squares mean difference −0.52%, 95% CI −0.67 to −0.38 [−5.7 mmol/mol, 95% CI −7.3 to −4.2; P < 0.001); greater reduction in HbA1c with BIL was maintained at 52 weeks. More BIL patients achieved HbA1c <7% (53 mmol/mol) at weeks 26 and 52 ( P < 0.001). With BIL versus glargine, nocturnal hypoglycemia rate was 60% lower, more patients achieved HbA1c <7% (53 mmol/mol) without nocturnal hypoglycemia at 26 and 52 weeks ( P < 0.001), and total hypoglycemia rates were lower at 52 weeks ( P = 0.03). At weeks 26 and 52, glucose variability was lower ( P < 0.01), basal insulin dose was higher ( P < 0.001), and triglycerides and aminotransferases were higher with BIL versus glargine ( P < 0.05). Liver fat content (LFC), assessed in a subset of patients ( n = 162), increased from baseline with BIL versus glargine ( P < 0.001), with stable levels between 26 and 52 weeks. CONCLUSIONS BIL provided superior glycemic control versus glargine, with reduced nocturnal and total hypoglycemia, lower glucose variability, and increased triglycerides, aminotransferases, and LFC

Wake Assessment at Three Water Bodies in Wisconsin, Illinois, and Missouri

"Natural and man-made waves play an important part of managing shorelines in lakes and riverine environments with a high degree of recreational activity. In this presentation, we will present findings of wave and wake activity in Lauderdale Lakes, WI, Fox River, IL, and Lake of the Ozarks, MO. Assessments will introduce the departure and potential difference in magnitude of natural and manmade waves along with mitigation efforts, both programmatic and project related. Presenter: Brian Valleskey, Geosyntec (Climate Change)""Natural and man-made waves play an important part of managing shorelines in lakes and riverine environments with a high degree of recreational activity. In this presentation, we will present findings of wave and wake activity in Lauderdale Lakes, WI, Fox River, IL, and Lake of the Ozarks, MO. Assessments will introduce the departure and potential difference in magnitude of natural and manmade waves along with mitigation efforts, both programmatic and project related. Presenter: Brian Valleskey, Geosyntec (Climate Change)

1044-P: The Impact of Basal Insulin Type, Prandial Dosing Plan, and Baseline Postprandial Glucose (PPG) on Glycemic Control after Treatment with Ultra-Rapid Lispro (URLi) or Humalog in Type 1 Diabetes: Planned Subgroup Analyses from PRONTO-T1D

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion and improve PPG control. In PRONTO-T1D, a phase 3, 26-week, treat-to-target study comparing URLi to Humalog in patients with T1D on a multiple daily injection regimen with insulin glargine or degludec, mealtime URLi was non-inferior to mealtime Humalog for change from baseline HbA1c and superior for PPG control, with a similar safety profile to Humalog. Randomization to treatment was stratified by basal insulin type, baseline HbA1c and prandial insulin dosing plan (carb counting, yes/no). The impact of these subgroups and baseline 2-hour PPG on the efficacy and safety of URLi was assessed from the double-blind treatment groups: mealtime URLi (n=451) and mealtime Humalog (n=442). No significant treatment-subgroup interactions were noted (all p&amp;gt;0.1) but occasional treatment differences were seen within each subgroup (p&amp;lt;0.05) (Table 1.). Numerically, results suggest that basal insulin type, starting PPG, and starting HbA1c, but not prandial dosing plan, may influence the magnitude of the HbA1c improvement and/or hypoglycemia risk reduction among patients treated with URLi. Disclosure J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company. J. Cho: None. T. Hardy: Other Relationship; Self; Eli Lilly and Company. Funding Eli Lilly and Company </jats:sec

1089-P: Ultra Rapid Lispro (URLi) Improves Postprandial Glucose (PPG) Control and Time in Range (TIR) in T1D Compared with Humalog (Lispro): PRONTO-T1D Continuous Glucose Monitoring (CGM) Substudy

Ambulatory glucose profiles were evaluated in 269 (22%) patients (pts) in PRONTO-T1D assigned to double-blind URLi (n=97) or lispro (n=99) given at start of the meal, or open-label URLi (n=73) given 20 min after the meal (URLi +20). Primary endpoint was incremental AUC0-2h (iAUC) after breakfast. Blinded CGM (Dexcom G4 Platinum) was worn for 14 days before baseline and week 26. Pts reflected main study population: mean A1C at week 26 was 7.15% - URLi, 7.12% - lispro, 7.35% - URLi+20. Compared to lispro, URLi had significantly smaller breakfast iAUC0-2h with estimated treatment difference (ETD) -28.1 mg.h/dL, p=0.048; more daytime TIR (71-180 mg/dL) ETD +43.6 min, p=0.020; and similar nighttime TIR. Time &amp;lt;50 mg/dL and &amp;gt;180 mg/dL were both numerically lower with URLi in daytime, with less time &amp;lt;50 mg/dL at nighttime vs. lispro: 7.0 vs. 12.6 min, p=0.023. PPG control in pts who marked meal times improved with URLi, while URLi +20 showed greater PPG variability (Figure). Glucose variability via CV and SD metrics was similar between groups, but less glucose variability was noticeable in CGM profiles of pts treated with URLi. When injected at the start of the meal, URLi resulted in significantly better PPG control and increased daytime TIR vs. lispro without increasing time in hypoglycemia. CGM results augment findings from PRONTO-T1D. Disclosure B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research &amp; Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. D. Cao: Employee; Self; Eli Lilly and Company. R. Liu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. T. Hardy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company. Funding Eli Lilly and Company </jats:sec