In JCI Insight: SGLT2 inhibitor promotes physiological changes that may explain fracture risk

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Inhibitors of sodium glucose cotransporter-2 (SGLT2) have been approved for treatment of type 2 diabetes due to their ability to improve glycemic regulation. Additional benefits of these inhibitors include weight loss and decreased blood pressure. Unfortunately, SGLT2 inhibitor use has also been linked to unfavorable side effects, including increased bone frac...ture risk. Jenny Blau and colleagues conducted a randomized, placebo-controlled study of the effects of the SGLT2 inhibitor canagliflozin in a cohort of healthy adults who remained at an in-patient facility during the trial. Compared to those on placebo, canagliflozin-treated subjects exhibited increases in serum phosphorus, FGF23, and parathyroid hormone, along with decreased 1,25-dihydroxyvitamin D. While the canagliflozin-associated changes during the course of the study were relatively small, over extended periods of time, these alterations have potential to adversely affect bone health. Observation of these parameters in patients may help identify those on SGLT2 inhibitors with the greatest risk of fracture.

Non-invasive monitoring of tumor vessel perfusion predicts immune checkpoint response

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Tissue biomarkers such as cytotoxic T cell:Treg ratio, PD-1 or PD-L1 expression can predict the efficacy of immune checkpoint blockade (ICB) therapies among different cancer types. However, the invasive and unstable nature of these biomarkers makes them unsuitable for monitoring individual responses to ICB throughout a course of treatment. Xichen Zheng and colleagues ...demonstrate that increased tumor vessel perfusion is a reliable predictor of early-stage ICB responses in solid tumor models. Both anti-CTLA4 and anti-PD-1 antibodies enhanced vessel perfusion in treatment-sensitive tumors. Moreover, anti-CTLA4 therapy increased tumor vessel perfusion prior to detectable changes in tumor size, as measured by Doppler ultrasonography. Non-invasive monitoring of tumor vessels may therefore provide valuable early-stage predictions of individual ICB response, enabling timely personalization of patient treatment plans.