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Greater Suppression of Glucagon, Lipolysis, and Ketogenesis with Insulin Glargine U300 as Compared with Glargine U100 in Type 1 Diabetes Mellitus.

Abstract
The aim of this study was to establish the effects of clinical doses of Gla-300 versus Gla-100 on suppression of glucagon, lipolysis, and ketogenesis in type 1 diabetes mellitus (T1DM). Eighteen persons with T1DM (age 40 ± 12 years, diabetes duration 26 ± 12 years, body mass index 23.4 ± 2 kg/m2, A1C 7.19% ± 0.52% [55 ± 6 mmol/mol]) were studied after 3 months of titration with Gla-300 and Gla-100 (randomized, crossover design) with a 24-h euglycemic clamp (s.c. injection of individual insulin daily doses used by subjects for previous 2 weeks, Gla-300 0.35 ± 0.08 and Gla-100 0.28 ± 0.07 U/kg). Gla-300 resulted in (1) less increase in insulin concentration for 0-12 h, but greater insulin concentration in 12-24 h (no differences for 24 h); (2) greater glucagon suppression; (3) greater prehepatic insulin-to-glucagon molar ratio, primarily in 12-24 h (ratio 1.78, 90% confidence intervals [CIs] 1.5-2.1); and (4) lower 24-h free fatty acid (0.81; 90% CI 0.73-0.89), glycerol (0.78; 90% CI 0.65-0.94), and β-hydroxybutyrate (0.72; 90% CI 0.58-0.90). Over the 24 h postinjection, as compared with Gla-100, clinical doses of Gla-300 exhibit greater suppressive effects on glucagon, lipolysis, and ketogenesis, whereas the effects on glucose metabolism are equivalent.
AuthorsPaola Lucidi, Francesca Porcellati, Patrizia Cioli, Paola Candeloro, Anna Marinelli Andreoli, Geremia B Bolli, Carmine G Fanelli
JournalDiabetes technology & therapeutics (Diabetes Technol Ther) Vol. 22 Issue 1 Pg. 57-61 (01 2020) ISSN: 1557-8593 [Electronic] United States
PMID31411498 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hypoglycemic Agents
  • Insulin Glargine
  • Glucagon
Topics
  • Adult
  • Diabetes Mellitus, Type 1 (blood, drug therapy)
  • Glucagon (blood)
  • Humans
  • Hypoglycemic Agents (administration & dosage)
  • Insulin Glargine (administration & dosage)
  • Lipolysis (drug effects)
  • Middle Aged

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