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Analyzing provocation data using pharmacometrics has shown powerful, enabling small studies. In preclinical drug development, high power is attractive due to the experiment sizes; however, insulin is not always available, which potentially impacts power and predictive performance. This simulation study was performed to investigate the implications of performing model\u2010based drug characterization without insulin. The integrated glucose\u2010insulin model was used to simulate and re\u2010estimated oral glucose tolerance tests using a crossover design of placebo and study compound. Drug effects were implemented on seven different mechanisms of action (MOA); one by one or in two\u2010drug combinations. 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