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SGLT2i: Adverse Events
Helping Patients With HF Manage Side Effects of SGLT2 Inhibitors

Released: October 27, 2023

Javed Butler
Javed Butler, MD, MPH, MBA
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Key Takeaways
  • In patients with heart failure taking an SGLT2 inhibitor, education on good genital hygiene can substantially lower the risk of getting a genitourinary infection.
  • A low threshold for adverse effect assessment and diagnosis is important in patients with heart failure taking an SGLT2 inhibitor.

In patients with heart failure (HF) with or without type 2 diabetes (T2D) who are taking sodium–glucose cotransporter 2 (SGLT2) inhibitors, while the risk is low, watching out for genitourinary (GU) infections, urinary tract infections (UTIs), and ketoacidosis, is prudent. With GU infections, there are 2 ways to look at the recent data. First, the risk of genital mycotic infection is about 3 times higher in patients who are taking an SGLT2 inhibitor; and second, both the EMPEROR-Reduced and EMPEROR-Preserved trials found that the absolute risk in patients with HF with a reduced or preserved ejection fraction was approximately 0.6 to 0.7 in the placebo arm vs 1.7 to 2.2 in the treatment arm. Therefore, the absolute risk is low and most of the patients are not going to develop a genital mycotic infection.

GU Infection Prevention When Using SGLT2 Inhibitors

From earlier diabetes trials with SGLT2 inhibitor, we have learned that by recommending patients practice good genital hygiene, washing and keeping the area dry, we can substantially lower the risk of GU infections. If a person taking an SGLT2 inhibitor develops a genital mycotic infection, we do not need to stop the SGLT2 inhibitor and should treat the infection either orally or locally. There are some patients (e.g., an elderly female patient with urinary incontinence or who wears a diaper) may will not be able to tolerate an SGLT2 inhibitor and may get recurrent genital mycotic infections, but these are rare patients. Therefore, it is important to raise awareness at the start of SGLT2 inhibitor treatment to manage expectations and promote early intervention to prevent GU infections.

SGLT2 Inhibitors and UTI Occurrence in Patients With HF

It is important to note that there is a difference between GU infection prevalence and UTI prevalence with SGLT2 inhibitor use. When compared to placebo, there is no significant increase in the occurrence of UTIs when using an SGLT2 inhibitor. That being said, for a patient not currently on an SGLT2 inhibitor who has an active UTI, it is best to wait before starting an SGLT2 inhibitor. If someone is developing more than one UTI while they are taking an SGLT2 inhibitor, remember to evaluate for other causes like undiagnosed kidney stones or uterine prolapse.

Ketoacidosis Concerns With SGLT2 Inhibitors

Healthcare professionals (HCPs) in cardiology do not often think about diabetic ketoacidosis (DKA), but there is an added layer of complexity when we have a person with uncontrolled T2D who presents with belly pain, nausea, vomiting, and general malaise. It is important to rule out DKA and have the patient do a fingerstick and check their glucose. If their fingerstick tells you that their blood glucose is very high, you know to send them to the emergency room with suspected DKA. With the use of SGLT2 inhibitors, the diagnosis of DKA becomes a little challenging, as there is an increased risk of DKA, but an individual’s blood glucose may be much lower than anticipated, leading to a delayed diagnosis. In the case I just described, if someone is taking an SGLT2 inhibitor, their glucose may not be 600 mg/dL, but rather 200 mg/dL, which may not trigger an automatic concern of DKA. Glucosuria is an on-target effect of SGLT2 inhibitors and can result in euglycemic ketoacidosis. While the blood glucose is not truly euglycemic, it is also not exorbitantly high, and therefore we may miss the diagnosis. So, what can we do about it?

On the diagnostic side, we must have a low threshold to assess ketone bodies. You may want to give your patients a card stating that they are on an SGLT2 inhibitor, so if they feel unwell and go to an urgent care or an emergency room, they can show the HCP that they are on an SGLT2 inhibitor, alerting them to the potential need to assess ketone bodies.

To prevent euglycemic DKA in individuals taking SGLT2 inhibitors, it is important to identify instances where changes in eating habits may occur. For patients taking insulin and, for whatever reason, are not going to eat normally, stopping the SGLT2 inhibitor is the simplest way to prevent the risk of developing DKA. For example, if a patient has nausea, vomiting, diarrhea, gastrointestinal problems, or is in the hospital for surgery and will be NPO or intubated for a certain amount of time, they should stop the SGLT2 inhibitor until post procedure. Once the person is up and about and eating normally for a day or so, then they can get started on an SGLT2 inhibitor again. Looking at the clinical trials, the risk of ketoacidosis was low, but considering the risks, having a low threshold for assessment and diagnosis, and prevention and mitigation is important in patients with HF.  

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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