Comparison of pharmacodynamics between insulin glargine 100 U/mL and insulin glargine 300 U/mL in healthy cats

Insulin glargine (IGla) is a synthetic human-recombinant insulin analog that is used routinely in people as a q24h basal insulin. The 300 U/mL (U300) formulation of IGla is associated with longer duration of action and less within-day variability, making it a better basal insulin compared with the 100 U/mL (U100) formulation. We hypothesized that in healthy cats, IGlaU300 has a flatter time-action profile and longer duration of action compared with IGlaU100. Seven healthy neutered male, purpose-bred cats were studied in a randomized, crossover design. Pharmacodynamics of IGlaU100 and IGlaU300 (0.8 U/kg, subcutaneous) were determined by the isoglycemic clamp method. The time-action profile of IGlaU300 was flatter compared with IGlaU100 as demonstrated by lower peak (5.6 +/- 1.1 mg/kg/min vs 8.3 +/- 1.9 mg/kg/min, respectively; P = 0.04) with no difference in total metabolic effect (ME; P = 0.7) or duration of action (16.8 h +/- 4.7 h vs 13.4 h +/- 2.6 h; P = 0.2). The greater fraction of ME in the 12-to 24-h period postinjection (35 +/- 23% vs 7 +/- 8% respectively; P = 0.048) and lower intraday GIR% variability (7.8 +/- 3.7% vs 17.4 +/- 8.2% respectively; P = 0.03) supports a flatter time-action profile of IGlaU300. There were no differences in onset and end of the action. In summary, although both formulations have a similar duration of action that is well below 24 h, the ME of IGlaU300 is more evenly distributed over a 24 h period in healthy cats, making it a better candidate for once-daily injection in diabetics compared with IGlaU100. (c) 2020 Elsevier Inc. All rights reserved.