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Additional important points represent a source of concern, such as the significantly higher rate of hospitalization for heart failure with saxagliptin reported in the SAVOR-TIMI 53 trial [58], the fact that the research regarding dutogliptininitially considered a promising selective DPP4 inhibitor [146] was abruptly discontinued without giving any reason [63] and the finding of hyperuricemia in patients treated with teneligliptin [129]

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Mechanical or inflammatory injury to the hypothalamus alters neuroendocrine secretion and contributes to systemic insulin resistance induced by inflammation/hyperglycemia, further impairing metabolic regulation and glucose uptake [60]

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