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Abstract   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_AUC 0‐4 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_AUC 0‐1 h  ratio 0.99 (95% confidence interval, 0.82; 1.22)], but with SC dosing M1_C max  and AUC 0‐24h  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.

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