SGLT2-inhibition increases total, LDL, and HDL cholesterol and lowers triglycerides: Meta-analyses of 60 randomized trials, overall and by dose, ethnicity, and drug type.

Background And Aims: Sodium glucose co-transporter 2 (SGLT2)-inhibitors were developed as glucose-lowering drugs. Surprisingly, SGLT2-inhibitors also reduced risk of cardiovascular disease. The impact of SGLT2-inhibitors on lipids and lipoproteins is unclear, but an effect might contribute to the observed lower cardiovascular risk.

Genetic variation in solute carrier family 5 member 2 mimicking sodium-glucose co-transporter 2-inhibition and risk of cardiovascular disease and all-cause mortality: reduced risk not explained by lower plasma glucose.

Aims: Treatment with sodium-glucose co-transporter 2 (SGLT2)-inhibitors reduces the risk of cardiovascular disease and mortality, but the mechanism is unclear. We hypothesized that a functional genetic variant in solute carrier family 5 member 2 (SLC5A2), known to be associated with familial renal glucosuria, would mimic pharmacological SGLT2-inhibition, and thus provide an opportunity to examine potential mediators of the effects on lower risk of cardiovascular disease and mortality.

Methods And Results: We examined 112 712 individuals from the Copenhagen City Heart Study and Copenhagen General Population Study (CCHS + CGPS), 488 687 from the UK Biobank, and 342 499 from FinnGen, genotyped for SLC5A2 rs61742739, c.

Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx.

Neurotensin (NT) is a neurohormone produced in the central nervous system and in the gut epithelium by the enteroendocrine N cell. NT may play a role in appetite regulation and may have potential in obesity treatment. Glucose ingestion stimulates NT secretion in healthy young humans, but the mechanisms involved are not well understood.