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

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/m 2 , 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.