What is it about?

In this mechanistic review, we major compared the current study progress of how GLP-1RA and SGLT-2i reduce cardiovascular complications in diabetic populations from their exclusive properties in the central nervous system. GLP-1RA were talked about their energy role in the brain responsible for energy homeostasis. On the other hand, we revealed the possible role of SGLT-2i, which has a small molecular weight, and liposolubility, could access the brain, and elicit cardiovascular activity. Both drugs have some similarities and also discrepancies, these topics were covered in our article.

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Why is it important?

Many clinical guidelines in diabetes management have recommended the GLP-1RA and SGLT-2i the first-line medication in diabetic patients at higher risk of acquiring cardiovascular complications like atherosclerotic coronary heart disease or at risk of heart failure(HF). We consider GLP-1RA with anti-atherosclerosis trait and SGLT-2i with HF-reduction properties possibly exert their effects in the central nervous system, which have been confirmed by many basic and clinical studies, especially in GLP-1RA, which could influence energy setpoint and balance through the hypothalamus. Still, there're only minor investigations in SGLT-2i, which are supposed to reduce the sympathetic nervous system's activity (SNS) and RAAS by many clinical studies. Thus, we discussed the mechanism of these two drugs on how their central effects have impacted or related to their reduced cardiovascular events in clinics. This is further to certain of our clinical decisions in these populations. We believe this may be a cornerstone in future drug development on targeting central autonomic nervous activity and rearrangement the metabolism and cardiovascular safety.


The breakthrough in developing anti-diabetic drugs with cardiovascular benefits has opened a new paradigm for researching the relationship between macrovascular complications and diabetes and paved us with a new era of treatment.

Dr. Song Wen
Shanghai Pudong Hospital

Read the Original

This page is a summary of: An Overview of Similarities and Differences in Metabolic Actions and Effects of Central Nervous System Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Sodium Glucose Co-Transporter-2 Inhibitors (SGLT-2is), Diabetes Metabolic Syndrome and Obesity, June 2021, Taylor & Francis,
DOI: 10.2147/dmso.s312527.
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