Recently, a friend in the pharmaceuticals business asked me about SGLT-2 Inhibitors. He wanted to know what a nephrologist thought of the drugs, and I expressed strong misgivings about potential complications.
I later gave a lecture on chronic kidney disease at a CME conference where I similarly decried this class of drugs, highlighting my concerns about dehydration, acute kidney injury, and genitourinary sepsis.
Well, I was wrong - sort of.
As it turns out, these drugs – empagliflozin and canagliflozin in particular – in randomized controlled trials, have demonstrated not only reductions in cardiovascular mortality for patients with known cardiovascular disease, but additionally reduced progression of kidney disease in diabetics. There are too many details to cover here, but it would behoove anyone prescribing these medicines to review these studies.
One highlight: a recent trial involving over 4000 patients with diabetes and overt proteinuria compared canagliflozin to placebo, specifically targeted at renal outcomes. The trial was stopped early because the renal benefits were so evident. There was a statistically significant reduction in the primary outcome, which was a composite of having to start dialysis, doubling serum creatinine, and death from renal or cardiovascular causes. This news is very exciting to nephrologists. It is reminiscent of our excitement related to the advent of ACE inhibitors and ARB’s.
All of that said - I wasn’t completely wrong. These drugs are diuretics. They do increase the risk of urinary tract infections and vaginal candidiasis. And there have been reports of Fournier’s gangrene also. As diuretics, especially when paired with ACE inhibitors and other diuretics and/or NSAIDs, they can lead to acute kidney injury. There are some signals in the data that canagliflozin in particular is associated with increased bone fractures and amputations, and some reports of “euglycemic” DKA (meaning DKA with a blood glucose <250). There is a bladder cancer warning associated with dapagliflozin. They cannot be given to type I diabetics. Canagliflozin and dapagliflozin can’t be given to patients with liver damage, but empagliflozin can.
While guidelines still favor metformin as first-line therapy, the data here is very compelling. There are some specific dosing guidelines to be followed and adverse effects to be considered, but I do believe now that increased use of this class of drug will likely help to stem the ever-rising tide of diabetic kidney disease.
Thomas Watson, MD is Board-Certified in Nephrology and Internal Medicine and practices in Birmingham with Nephrology Associates, P.C.
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