Treatment with bariatric surgery, GLP-1 receptor agonists or SGLT2 inhibitors reduces major adverse cardiovascular events in type 2 diabetes beyond glucose lowering, as shown in meta-analysis including over 169,000 patients.
Do bariatric surgery, GLP-1 receptor agonists, or SGLT2 inhibitors improve cardiovascular outcomes and reverse insulin resistance in type 2 diabetes through nutrient off-loading and ectopic fat reduction?
The paper proposes that the cardiovascular benefits of bariatric surgery, GLP-1 RAs, and SGLT2 inhibitors in type 2 diabetes are driven by nutrient off-loading and reduction of ectopic fat.
Effect estimate: Risk reduction (meta-analysis based on 169,513 participants)
Insulin resistance in type 2 diabetes is associated with cardiovascular disease. Nutritional overload, hyperinsulinemia, and physical inactivity are the major etiological factors driving the development of insulin resistance. In an obesogenic environment, insulin resistance has been proposed to protect the body against toxic fuel overload, hyperinsulinemia-induced injury, and metabolic stress. Insulin resistance has been further hypothesized to defend the heart and blood vessels against fuel overload when an individual is chronically overeating. Recent landmark cardiovascular outcome trials in type 2 diabetes show major improvements in cardiovascular disease outcomes after treatment with GLP-1 receptor agonists or SGLT2 inhibitors. Bariatric surgery achieves even greater improvements in cardiovascular disease outcomes than treatments with these newer pharmacological agents. It had been previously predicted that glucose-lowering approaches that normalize whole-body energy balance have the greatest potential to improve cardiovascular outcomes in type 2 diabetes. This review hypothesizes that treatment with bariatric surgery, GLP-1 receptor agonists, or SGLT2 inhibitors lowers glucose and nutritional off-loading, normalizes whole-body energy balance, and reduces ectopic fat depositions. This plays a central role in the dramatic reduction in cardiovascular disease and the reversal of insulin resistance in type 2 diabetes, which are observed after these three treatments.
Joseph A. M. J. L. Janssen (Wed,) conducted a review in Adults with type 2 diabetes and insulin resistance at risk for cardiovascular disease. Bariatric surgery, GLP-1 receptor agonists, or SGLT2 inhibitors vs. Older antihyperglycemic treatments or placebo was evaluated on Major adverse cardiovascular events (MACEs) (Risk reduction (meta-analysis based on 169,513 participants)). Treatment with bariatric surgery, GLP-1 receptor agonists or SGLT2 inhibitors reduces major adverse cardiovascular events in type 2 diabetes beyond glucose lowering, as shown in meta-analysis including over 169,000 patients.