Sodium-glucose-cotransporter 2 inhibitors (SGLT2is) demonstrate large cardiovascular benefit in both diabetic and non-diabetic, acute and chronic heart failure patients. These inhibitors have on-target (SGLT2 inhibition in the kidney) and off-target effects that likely both contribute to the reported cardiovascular benefit. Here we review the literature on direct effects of SGLT2is on various cardiac cells and derive at an unifying working hypothesis. SGLT2is acutely and directly (1) inhibit cardiac sodium transporters and alter ion homeostasis, (2) reduce inflammation and oxidative stress, (3) influence metabolism, and (4) improve cardiac function.
Results: Compared with placebo, canagliflozin 100 mg reduced SBP by 3.43 mmHg and DBP by 1.05 mmHg. Canagliflozin 100 mg increased LDL-C by 0.10mmol/l and HDL cholesterol (HDL-C) by 0.05 mmol/l. Compared with placebo, canagliflozin 300 mg reduced SBP by 4.75 mmHg and DBP by 1.69 mmHg. Canagliflozin 300 mg increased LDL-C by 0.16 mmol/l and HDL-C by 0.06 mmol/l. Compared with canagliflozin 100 mg, canagliflozin 300 mg further reduced SBP by 1.21 mmHg and DBP by 0.64 mmHg, and further increased LDL-C by 0.06 mmol/l and HDL-C by 0.02 mmol/l. Compared with placebo and canagliflozin 100 mg, canagliflozin 300 mg increased the risk of UTI.
Conclusion: The current meta-analysis provides new evidence on different doses of canagliflozin as an antihypertensive agent in T2DM complicated by hypertension; however, LDL-C and the risk of UTI should be monitored.
“Then they evaluated how treatment with the sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (Empa) improved blood vessel function and reduced arterial stiffness in aged male mice.”
Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin
Limitation:
Treatment selection was not randomized.
Conclusion:
As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin.
Importantly, mean follow up was only 12 months. Since CVD development is a slow process, I’d only expect those relative risks of heart failure to further diverge (and maybe even see some lowered comparative risks for stroke/MI in the SGLT2i group?) as time goes on. Hopefully they’ll continue to follow these cohorts to see if that’s true.
I wonder what the relative rate of genital infections in men vs women was in the SGLT2i group?
Yes - I have also wondered about this… I’ve never heard of men getting UTIs, so I suspect its almost all women. But if someone knows differently, please post.
Newer glucose‐lowering drugs and risk of dementia: A meta‐analysis of cardiovascular outcome trials
We included randomized placebo-controlled cardiovascular and renal outcome trials that reported all-cause dementia or vascular dementia (see definitions in Table S1) associated with DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors among adults with and without T2D.
SGLT2 inhibitors were significantly associated with a decreased risk for vascular dementia (OR, 0.11; 95% CI, 0.02–0.66), compared with placebo.
