Episode 138: SGLT-2 Inhibitors in heart failure

Episode 138: SGLT-2 Inhibitors in heart failureFuture doctor Enuka explains the use of sodium-glucose-linked cotransporter-2 inhibitors (SGLT-2 inhibitors) in heart failure. Dr. Arreaza adds his experience with these medications and emphasizes their role as an effective treatment for type 2 diabetes.  Written by  Princess Enuka, MSIV, Ross University School of Medicine. Editing by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Intro:Heart failure is a major medical condition that affects millions of people worldwide. It is one of the leading causes of hospitalization and death in developed countries. Recently, SGLT2 inhibitors have emerged as a promising treatment option for heart failure. Today, we will discuss their benefits, their effectiveness, and their adverse effects.SGLT2 inhibitors, also known as sodium-glucose-linked cotransporter-2 inhibitors, are a relatively novel class of drugs that have shown promise in heart failure treatment. This transporter reabsorbs glucose from the glomerular filtrate back into the bloodstream. Under normal circumstances, SGLT-2 reabsorbs 100% of the filtered glucose unless it is saturated (as in hyperglycemia) or blocked by medications. SGLT2 inhibitors increase the amount of glucose excreted in the urine, which leads to blood glucose reduction. Examples include empagliflozin, dapagliflozin, and canagliflozin.SGLT-2 inhibitors have become a first-line therapy for diabetes mellitus. I heard before that it was used in Europe for T1DM, but it seems like they are no longer used, according to my most recent review of articles. SGLT2 inhibitors are not approved by the FDA for use in type 1 diabetes due to the risk of DKA. Princess, besides the benefits in diabetes, what else did you find in your review?Benefits/Efficacy:SGLT2 inhibitors have additional benefits beyond their glucose-lowering effects. One of the benefits of SGLT2 inhibitors is their ability to increase myocardial energy production, alleviate systemic microvascular dysfunction, and improve systemic endothelial function. Natriuresis and glucosuria mediated by SGLT2 inhibitors have been shown to lower cardiac pre-load and reduce pulmonary congestion and systemic edema, which is beneficial for heart failure management.Studies have shown that these drugs can also improve cardiovascular outcomes in patients with heart failure with a reduced ejection fraction. Some studies:The EMPEROR-Reduced trial demonstrated that empagliflozin, brand name Jardiance®, reduced the risk of cardiovascular death and hospitalization for heart failure in patients with reduced ejection fraction by 25% compared to placebo. Several clinical trials have also shown that this result is significant whether patients have type 2 diabetes or not. Also, in a multicenter, double-blind, randomized, placebo-controlled trial in patients with heart failure, treatment with dapagliflozin, brand name Farxiga®, improved heart failure-related symptoms and physical limitations after only 12 weeks of treatment. Patients treated with dapagliflozin had a significant, clinically meaningful improvement in the 6-minute walking test distance. The magnitude of these benefits was statistically and clinically significant, spanning all subgroups categorized. This included patients with and without type 2 diabetes and those with an ejection fraction above or below 60%.Anecdote:During a previous clinical rotation, I had a patient taking Jardiance for heart failure. He also had a history of chronic kidney disease and managed his condition well with medications and regular follow-ups. Interestingly, he was prescribed Jardiance®, which I initially believed was solely for diabetes management. When I asked him about it, he explained that his cardiologist prescribed Jardiance specifically for his heart. At the time, I did not understand the rationale behind prescribing Jardiance®, especially since the patient did not have type 2 diabetes. But after researching the medication, I figured that his cardiologist had chosen Jardiance® due to its demonstrated benefits in reducing the risk of cardiovascular death and hospitalization for heart failure. Although initially considered to be only glucose-lowering agents, the effects of SGLT2 inhibitors have expanded far beyond that. Their use has expanded to include heart failure and chronic kidney disease, even in patients without diabetes. It is, therefore, essential that cardiologists, diabetologists, nephrologists, and primary care physicians are familiar with this drug class.Adverse effects:It is worthwhile to note that SGLT2 inhibitors are not typically used as first-line treatment for heart failure, and not all patients with heart failure are appropriate candidates for these medications. SGLT2 inhibitors are generally well-tolerated, but they can cause adverse effects. Genital and urinary tract infections and euglycemic diabetic ketoacidosis are the most common side effects experienced by patients. The incidence of these adverse effects is generally low and can be managed with appropriate monitoring and treatment. In addition, SGLT2 inhibitors can also cause dehydration, electrolyte imbalances, hypotension, and acute kidney injury (AKI). These imbalances are more common in elderly patients or those with renal impairment, like the patient I discussed earlier. Genital yeast infections: Diabetes is also a risk factor for genital yeast infections because glucose in the urine is used as a substrate by microorganisms to grow in the GU tract. UTI and genital yeast infections are prevented by staying well hydrated while taking these meds. Increased intake of water will dilute the urine and decrease the concentration of glucose in urine. UTI/genital yeast infections are treated as usual, and the SGLT-2 can be resumed after infections are treated. In case of recurrence, the clinician may consider discontinuation of medication based on a case-by-case assessment. Patients using SGLT2 inhibitors for treatment should have regular follow-ups with their physicians for the early detection of adverse effects. Bladder cancer: It is not clear if chronic glucosuria is tumorigenic since there are no long-term data. In clinical trials, 10 cases of bladder cancer were diagnosed among dapagliflozin users, five of which occurred only in the first six months of treatment. The FDA has recommended postmarketing surveillance studies. Dapagliflozin is not recommended in patients with active bladder cancer. Bone fractures and limb amputation: One trial (CANVAS) demonstrated an increased incidence of bone fractures and limb amputations among users of canagliflozin, but another trial (CREDENCE) did not demonstrate such an increased incidence of bone fractures or limb amputations. This increased risk has not been proven with empagliflozin. Summary: SGLT2 inhibitors have shown promise in heart failure treatment, particularly in patients with a reduced ejection fraction. Even though the specific mechanism of action through which they work on the cardiovascular system is currently unknown, they have been shown to reduce the risk of hospitalization for heart failure and cardiovascular death in several clinical trials. These medications lower blood glucose levels and have other beneficial effects on the cardiovascular system that make them good options for the management of heart failure.____________________Conclusion: Now we conclude episode number 138, “SGLT-2 inhibitors in heart failure.” Princess explained that SGLT-2 inhibitors have many benefits that go beyond their glucose-lowering properties. Recently, the use of SGLT-2 inhibitors has been extended to include heart failure with reduced ejection fraction and chronic kidney disease, even in patients without diabetes. Dr. Arreaza also explained that FDA has not approved the use of SGLT-2 inhibitors for the treatment of type 1 diabetes because of the reported increased risk of diabetic ketoacidosis or DKA. There is ongoing research about additional uses of SGLT-2 inhibitors, and we are looking forward to hearing more about these medications in the future.This week we thank Hector Arreaza and Princess Enuka. Audio editing by Adrianne Silva.Even without trying, every night, you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you. Send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! _________________Links:Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424. https://pubmed.ncbi.nlm.nih.gov/32865377/Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255-323. https://pubmed.ncbi.nlm.nih.gov/31497854/Heerspink HJL, Perkins BA, Fitchett DH, et al. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016;134(10):752-772. https://pubmed.ncbi.nlm.nih.gov/27470878/Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(4):422-434. https://pubmed.ncbi.nlm.nih.gov/32000955/Nassif, M. E., et al. (2020). The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: A multicenter randomized trial. Nature Medicine, 27(11), 1954-1960. https://doi.org/10.1038/s41591-021-01536-xRoyalty-free music used for this episode: "Tempting Tango." Downloaded on October 13, 2022, from https://www.videvo.net/ Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!