title: Comparison of Insulin Glargine 300 Units/mL and 100 Units/mL in Adults With Type 1 Diabetes: Continuous Glucose Monitoring Profiles and Variability Using Morning or Evening Injections.
abstract: The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL (Gla-300) or glargine 100 units/mL (Gla-100) in the morning or evening, in combination with mealtime insulin.
  
  
  
  In this 16-week, exploratory, open-label, parallel-group, two-period crossover study (clinicaltrials.gov identifier NCT01658579), 59 adults with type 1 diabetes were randomized (1:1:1:1) to once-daily Gla-300 or Gla-100 given in the morning or evening (with crossover in the injection schedule). The primary efficacy end point was the mean percentage of time in the target glucose range (80-140 mg/dL), as measured using continuous glucose monitoring (CGM), during the last 2 weeks of each 8-week period. Additional end points included other CGM glycemic control parameters, hypoglycemia (per self-monitored plasma glucose [SMPG]), and adverse events.
  
  
  
  The percentage of time within the target glucose range was comparable between the Gla-300 and Gla-100 groups. There was significantly less increase in CGM-based glucose during the last 4 h of the 24-h injection interval for Gla-300 compared with Gla-100 (least squares mean difference -14.7 mg/dL [95% CI -26.9 to -2.5];P= 0.0192). Mean 24-h glucose curves for the Gla-300 group were smoother (lower glycemic excursions), irrespective of morning or evening injection. Four metrics of intrasubject interstitial glucose variability showed no difference between Gla-300 and Gla-100. Nocturnal confirmed (<54 mg/dL by SMPG) or severe hypoglycemia rate was lower for Gla-300 participants than for Gla-100 participants (4.0 vs. 9.0 events per participant-year; rate ratio 0.45 [95% CI 0.24-0.82]).
  
  
  
  Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval, smoother average 24-h glucose profiles irrespective of injection time, and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100.
authors.affiliation: Park Nicollet International Diabetes Center, Minneapolis, MN richard.bergenstal@parknicollet.com.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
authors.affiliation: AMCR Institute, Escondido, CA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Bailey
authors.affiliation: Biomedical Informatics Consultants LLC, Potomac, MD.
authors.forename: David
authors.initials: D
authors.lastname: Rodbard
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Ziemen
authors.affiliation: BDM Consulting Inc., Somerset, NJ.
authors.forename: Hailing
authors.initials: H
authors.lastname: Guo
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Muehlen-Bartmer
authors.affiliation: Oregon Health & Science University, Portland, OR.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ahmann
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D023381:Endpoint Determination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D000069036:Insulin Glargine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine