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SGLT2i in HF: Medication Adjustments
Considerations for Medication Adjustments in Patients With Heart Failure Initiating or Currently Taking SGLT2 Inhibitors

Released: November 13, 2023

Lee R. Goldberg
Lee R. Goldberg, MD, MPH, FACC, FAHA, FHFSA
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Key Takeaways
  • Attention to volume status is required when SGLT2 inhibitors, ARNIs, and loop diuretics are used in combination because of their concomitant effects to promote diuresis.
  • SGLT2 inhibitors rarely cause hypoglycemia in absence of concomitant insulin and/or secretagogue therapy.

When initiating a sodium-glucose cotransporter-2 (SGLT2) inhibitor in a patient with heart failure, there are many factors to consider when it comes to concomitant medication adjustments. Things such as volume status, upcoming procedures, and a patients’ additional antiglycemic medications should be evaluated when initiating or managing a patient with heart failure on an SGLT2 inhibitor.

Diuretic Dose Adjustments
As clinicians, how do we decide when to prospectively reduce the dose of loop diuretic when initiating an SGLT2 inhibitor? It is important to consider volume status, as SGLT2 inhibitors, angiotensin receptor-neprilysin inhibitors (ARNIs), and loop diuretics used in combination potentiate diuresis. Even our mineralocorticoid receptor antagonists (MRAs) may have some diuretic effects when used in combination with other guideline-directed medical therapies. We are potentially decreasing a patient’s intravascular volume through multiple different methods, and therefore cutting down the diuretic dose preemptively in appropriate patients may reduce the risk of hypotension and hypovolemia.

It is also important to instruct patients to hold their diuretics when they develop symptoms of dehydration such as lightheadedness, weakness, and orthostasis especially in the setting of decreasing weight. If they develop symptoms, cutting back on loop diuretic makes sense. In my practice we have a protocol based on our clinical experience where we reduce diuretic doses by roughly 50% when initiating an SGLT2 inhibitor. We worry about dehydration, and preemptively reduce an individual’s diuretic dose. After this dose reduction, we do twice weekly calls and daily weight checks to ensure patients are not volume overloaded. Some of those patients do require that higher diuretic dose, and we go back up, but we have found that a lot of them do not once an SGLT2 inhibitor is on board. We also review electrolytes and renal function within the first two weeks after SGLT2 inhibitor initiation.

In the EMPEROR-Reduced and EMPEROR-Preserved trials, empagliflozin reduced the requirement for intensification of diuretics due to worsening heart failure. Clinical trials with dapagliflozin showed that patients on a diuretic at baseline were likely to have their diuretic dose decreased or discontinued. This implies the need for careful assessment of volume status when initiating SGLT2 inhibitors, and I personally would err on the side of caution to prevent volume contraction.  

When Should SGLT2 Inhibitor Therapy Be Paused?
Until recently, when a person on a SGLT2 inhibitor came into the hospital, the SGLT2 inhibitor would be stopped or held. In reality, that is not always required. Patients with heart failure without any contraindications to SGLT2 inhibitors on admission should continue their guideline-directed medical therapy. The EMPULSE trial showed that hospital initiation of SGLT2 inhibitors improved heart failure outcomes, so we know that it is safe to use these agents in the hospital in medically appropriate patients. That being said, there are several instances where SGLT2 inhibitors should be held. When we think about patients undergoing surgery or with conditions leading to restricted food intake or dehydration, they are at higher risk for euglycemic diabetic ketoacidosis (DKA) while taking an SGLT2 inhibitor.

Therefore, SGLT2 inhibitors should be stopped and then restarted after planned surgery when the patient is eating and drinking normally. If somebody is going to go for surgery, stopping the SGLT2 inhibitor for a few days and then restarting once the individual has recovered makes sense to avoid any adverse events. In addition to major surgical procedures, SGLT2 inhibitors should be stopped in patients with an acute serious medical illness, emergency surgery, or a condition that leads to volume depletion or dehydration (eg, unable to eat/drink normally, diarrhea/vomiting, and fever), or in the instance of a major infection. Holding SGLT2 inhibitors in these instances will help avoid euglycemic DKA and will have minimal if any impact on heart failure outcomes.

SGLT2 Inhibitor Utilization, Hypoglycemia, and Diabetes Medication Adjustments
SGLT2 inhibitors alone are unlikely to cause hypoglycemia due to their mechanism of action. SGLT2 inhibitors act by reducing renal tubular glucose reabsorption, resulting in a decrease in blood glucose without stimulating insulin release. When a person is hyperglycemic, glucose spills into the urine. If a person does not have high glucose to begin with, then glucose does not spill into the urine and there is no resulting blood glucose decrease.

However, when an SGLT2 inhibitor is combined with either secretagogues or with insulin in a patient with a history of diabetes, hypoglycemia can occur, and background therapies might need to be adjusted to prevent it. From a practical perspective, what should be done? In my opinion, I would say that if someone has a history of hypoglycemia in the past with their hemoglobin A1C well controlled at 7%, and they are initiating an SGLT2 inhibitor, I would stop their sulfonylurea completely. I would reduce their dose of insulin by 30%, follow their finger sticks at home, and have them adjust up and down as needed. Since DPP‑4 inhibitors and sulfonylurea do not have documented cardiovascular benefit, these medications can be stopped and thereby decrease polypharmacy and decrease cost. In patients who do not have a history of hypoglycemia and with a hemoglobin A1C of around 9%, I would consider adding the SGLT2 inhibitor to their background medication use for better glucose control. Partnering with the primary care physician or endocrinologist is critical in providing coordinated care in patients with both diabetes and heart failure.

Interested in learning more? View the CME-certified webinar from HFSA 2023, download the slideset, or view our other ClinicalThought commentary.

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