Equipotency of insulin glargine 300 and 100 U/mL with intravenous dosing but differential bioavailability with subcutaneous dosing in dogs

Aims: Insulin glargine 300 U/mL (Gla-300) contains the same units versus glargine 100 U/mL (Gla-100) in three-fold lower volume, and higher subcutaneous (SC) doses are required in people with diabetes. To investigate blood glucose (BG) lowering potency, Gla-300 and Gla-100 were compared after intravenous (IV, for 4 h) and SC (for 24 h) injection in healthy Beagle dogs. Materials and methods: The dose of 0.15 U/kg Gla-300 and Gla-100 was injected IV in 12 dogs. BG, C-peptide, glucagon and the active metabolite 21A-Gly-human insulin (M1; liquid chromatography-tandem mass spectrometry method) were measured. Twelve other dogs were studied after SC injection of 0.3 U/kg Gla-300 and Gla-100. Results: After IV injection, Gla-300 and Gla-100 were equally potent [BG_AUC0-4 h ratio 1.01 (95% confidence interval, 0.94; 1.09)]. After SC injection, BG decreased slower and less with Gla-300. Similar metabolism of Gla-300 and Gla-100 to M1 occurred with IV dosing [M1_AUC0-1 h ratio 0.99 (95% confidence interval, 0.82; 1.22)], but with SC dosing M1_Cmax and AUC0-24h were 44% and 17% lower; mean residency time and bioavailability were 32% longer and 50% lower, with Gla-300. Conclusions: IV Gla-300 and Gla-100 have the equivalent of BG-lowering potency and M1 metabolism. SC Gla-300 has lower M1 bioavailability with a reduced BG-lowering effect and need for greater doses versus Gla-100.