Just Go With the Flo(zin): SGLT2i Should be added to A Few, Some, Most, All HFrEF Patients?
Presenter: Glenn Herrington, PharmD, BCCP, BCPS, CDCES, CPP
Glenn Herrington, clinical pharmacist from Wilmington, NC, reviewed data from the diabetes cardiovascular outcomes trials (CVOTs) (EMPA-REG outcome,1 Canvas Program,2 Declare-TIMI 58,3 and Vertis CV4) for several SGLT2 inhibitors, looked at more recent trials for patients that have heart failure with reduced ejection fraction (HFrEF) (the DAPA-HF trial5 and the EMPEROR-reduced trial6) with and without type 2 diabetes, and considered safety concerns, to decide in which patients these medications should be used.
In the CVOTs, for the primary endpoints of major adverse cardiovascular events (MACE) and cardiovascular (CV) death outcomes, for the trials of 4 SGLT2 inhibitors, there were mixed results. But for the secondary endpoint of hospitalization for heart failure, there is a signal across the board for all of these medications, with about a 30% reduction in risk of hospitalization for heart failure.
Dr. Herrington said because these are secondary endpoints it is important to remember that they really just drove further hypothesis testing, but that the results led to their more recent trials.
In the HFrEF trials, the primary endpoints were slightly different, hospitalization for heart failure or urgent heart failure visits, and also CV death. The results here were mixed for the CV death outcome, but again there was significant reduction (almost 30%) in hospitalization for heart failure. According to Dr. Herrington, “It really shows that there’s something about these medications regardless of whether a patient has type 2 diabetes. It’s not necessarily the glucose reduction or a diuretic effect. There’s something else going on that really has this benefit for patients.”
There are some important contraindications or considerations to keep in mind before starting patients on these medications. SGLT2 inhibitors should not be used in patients with type 1 diabetes or who are allergic to SGLT2 inhibitors. These medications are not approved for patients who are on dialysis, and there is limited data on lactation and pregnancy.
For disease-related concerns, renal function is one concern, and there are different renal cutoffs for the different medications. Dr. Herrington said a good rule of thumb is less than 30 mL/min.
For acutely ill or fasting diabetic patients, SGLT2 inhibitors increase the risk of ketoacidosis, so patients should be informed to hold the medication if they become ill or are not eating or drinking. This also applies to hospitalized patients, so if planned procedures are coming up in the next few days the medications should be held. And if they are acutely ill, they should not be on these medications.
More recently, a different trial for a different SGLT2 inhibitor showed SGLT2 inhibitors can be initiated in hospitalized patients,7 especially those hospitalized for acute heart failure exacerbation, those being taken off IV diuretics, and those transitioning to an oral regimen to prepare for discharge.
Hypotension can also be a concern, especially for patients already on a diuretic. Other adverse effects patients should be informed of include polyuria or dysuria; female diabetic patients with a history of genital mycotic infections should be aware these medications can worsen that; hypovolemia or acute kidney injury are a concern; hypoglycemia for diabetic patients but only if they’re on a sulfonylurea or insulin; ketoacidosis in fasting patients; necrotizing fasciitis is a rare side effect; and increased risk of bone fracture was shown in some trials.
In summary, Dr. Herrington said, “I don’t think that we should be using SGLT2 inhibitors in every single heart failure medication, but we certainly should be considering them for all of our patients with HFrEF regardless whether they have type 2 diabetes, especially for that reduction in risk of hospitalization for heart failure.”
Glen Herrington, PharmD, reported he has no relevant disclosures.
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