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Slowing the ramp to the label cadence (2.5 mg start, 2.5 mg steps, four-week holds) dropped that to mid-single digits at every maintenance dose, at no cost to the 12-week result, and the dedicated slow-titration trial reached placebo range. Reaching 15 mg is not the problem
368 Astrocytes exposed to excessive ammonium start to generate aberrant Ca 2+ signals, which may cause excitotoxic release of glutamate
Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49)
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