Topic Discussion: SGLT-2 Inhibitors: An update

The glucoretics SGLT-2 inhibitors have really come with a wave to improve the outcomes in diabetic patients, especially cardio-vascular and renal outcomes. I had the pleasure to listen to Inzucchi SE recently on this topic and the science has really taken off.

Here is a summary of what is happening in the world of SGLT-2 inhibitors and what we need to know as nephrologists.

SLGT-2 inhibitors overall(  all of them) only have a minor to modest effect on A1C reduction. For anything, it might even stay the same after 12 weeks on the drug. This doesn’t translate into the benefits we see in trials. Regardless of the A1C being only modestly decreased, the cardiac benefits are amazing.

Even though they have a weight loss effect( usually just 2kg total no matter what), they are not approved for weight loss

Even though they have a significant bp effect, not approved for BP management

Obviously, they are not going to work if you have no URINE, so unclear benefit in ESRD patients

All trials, from CANVAS to EMPA-REG(empagliflozin), the cardiovascular benefits have been astounding- decreased number of MACE events( MI, stroke, cardiac event).

What the cardiologist world is excited about is also the decreased CHF admissions and readmissions ( perhaps due to the naturetic effect of the agent acting as a proximal tubule diuretic without really increasing renin-aldo axis)—making it an amazing drug for volume management. Recent studies have also shown increase in HCT with the drug use showing it’s effect on plasma volume.  Ongoing trials might shed light on CHF management in diabetics and non-diabetics with this agent. A recent review summarizes this.

Renal outcomes in EMPA-REG, initial decrease in GFR was reversible – related to the hyperfiltration decrease( similar to ACEI/ARB). But hard renal outcomes, 46% decrease in  doubling of crt, RRT or renal death. In addition, decrease in macro and micro-albuminuria as well.

CANVAS study- with a different drug- also similar MACE outcomes as EMPA-REG, but component of MACE individual were less pronounced. Comparable CHF benefits. Canaglifozin related CANVAS had more amputations and fractures as a major side effect that EMPA-REG(empagliflozin) data didn’t show that when re done to look for it; unclear why one drug does it and other doesn’t.  Visual abstract from NephJC

CANVAS Renal outcomes…40% reduction with agent with change in EGFR, dialysis and death-almost similar.

Should we start using this drug in diabetic patients with CKD? Or even CKD patients without DMII given significant cardio-vascular and renal benefit. When cost analysis was done, empagliflozin use resulted in higher total lifetime treatment costs ($371,450 versus $272,966) but yielded greater QALYs (10.712 vs. 9.419) compared to standard treatment. This corresponded to an ICER of $76,167 per QALY gained. This suggested that empagliflozin would be cost-effective in 96% of 10,000 iterations assuming a willingness-to-pay threshold of $100,000 per QALY gained.

Here is a nice review on both drugs and effects.

If we start prescribing as nephrologists, likely will be empagliflozin and dose of 10mg given similar effect and monitor for what effects? As might not change A1C anyway—more long term benefits such as cardio-vascular and renal effects.

We truly have entered a new era!!