<scp>S</scp>odium‐glucose co‐transporter‐2 inhibitors and protection from cardiovascular death: Is it all about heart failure?

Caruso, Irene; Cignarelli, Angelo; Laviola, Luigi; Giorgino, Francesco

doi:10.1111/dom.14444

Cited by 2 publications

(1 citation statement)

References 5 publications

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“…In light of this evidence, these therapies have opened a new paradigm not only for the management of altered glucose metabolism in T2D but also in consideration of their pleiotropic effects ( 1 , 20 ). Furthermore, both randomized control trials (RCTs) and real-world observational studies have reported improvements in all-cause mortality and CV mortality with both drug classes ( 21 , 22 ) compared with other glucose-lowering therapies, even though the mechanisms involved have yet to be completely elucidated ( 23 – 25 ). Importantly, significant effects are ascribed to both medications in terms of modification of body composition involving body fat mass ( 26 , 27 ), body water content ( 28 ), skeletal mass ( 29 ), and bone mineral density ( 30 , 31 ), as well as the impact on the function of different organs such as the brain ( 32 ), heart ( 32 , 33 ) and pancreas ( 5 ), suggesting a possible involvement of multiple endocrine axes.…”

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confidence: 99%

Mini Review: Effect of GLP-1 Receptor Agonists and SGLT-2 Inhibitors on the Growth Hormone/IGF Axis

et al. 2022

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Accumulating evidence supports the early use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose transporter-2 inhibitors (SGLT-2is) for the treatment of type 2 diabetes. Indeed, these compounds exert numerous pleiotropic actions that favorably affect metabolism and diabetes comorbidities, showing an additional effect beyond glucose control. Although a substantial amount of knowledge has been generated regarding the mechanism of action of both drug classes, much remains to be understood. Growth hormone (GH) is an important driver for multiple endocrine responses involving changes in glucose and lipid metabolism, and affects several tissues and organs (e.g., bone, heart). It acts directly on several target tissues, including skeletal muscle and bone, but several effects are mediated indirectly by circulating (liver-derived) or locally produced IGF-1. In consideration of the multiple metabolic and cardiovascular effects seen in subjects treated with GLP-1RAs and SGLT-2is (e.g., reduction of hyperglycemia, weight loss, free/fat mass and bone remodeling, anti-atherosclerosis, natriuresis), it is reasonable to speculate that GH and IGF-1 may play a about a relevant role in this context. This narrative mini-review aims to describe the involvement of the GH/IGF-1/IGF-1R axis in either mediating or responding to the effects of each of the two drug classes.

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