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Professor of Medicine
Division of Endocrinology
Department of Medicine
Duke University Medical Center
Duke Clinical Research Institute
Durham, North Carolina
Jennifer B. Green, MD, has disclosed that she has received consulting fees from AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Novo Nordisk, Pfizer, and Sanofi/Lexicon and funds for research support from AstraZeneca, Boehringer Ingelheim/Lilly, Merck, Roche, and Sanofi/Lexicon.
In this commentary, endocrinologist Jennifer B. Green, MD, discusses why healthcare professionals should have a high index of suspicion for heart failure (HF) in patients with type 2 diabetes (T2D) and the evolving use of SGLT2 inhibitors (SGLT2i) in patients with or at risk for HF. A webinar is available where expert faculty discuss the cardiovascular and renal protective effects of SGLT2i and their ability to reduce HF risk in your patients with T2D. Slides from the webinar are also available for self-study or to use in your noncommercial presentations.
Until the FDA mandated that cardiovascular outcomes be studied in trials of new agents for T2D, we did not appreciate how common HF is in diabetes. Although we were aware of the need to evaluate for and prevent atherosclerotic cardiovascular disease, guidelines did not emphasize the need to screen for or intervene to reduce the risk of HF in T2D.
Determining Which Patients With T2D Are at High Risk for HF
How can we identify patients with T2D who are at high risk for HF, and how can we diagnose HF early, perhaps even before patients develop HF-related symptoms? I think this is a global problem for primary care professionals as well as for endocrinologists.
Currently, the use of formal screening protocols to identify patients with T2D who should be seen by a cardiologist remains controversial, and utilization of echocardiography as a screening mechanism has not been considered cost-effective. However, recent American College of Cardiology/American Heart Association guidelines suggest that biomarkers like N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin could be considered as a means of identifying very high–risk patients. They might also be used to identify patients with stage B HF, in which structural heart abnormalities are present but there are no HF symptoms.
In my practice, I currently do not routinely order such biomarkers in patients with T2D, but I think I will start to in very high–risk patients. That’s because by the time symptoms and physical examination suggest HF, the person often has significant cardiac dysfunction. However, I will proceed with caution, as biomarkers such as NT-proBNP are imperfect screening tools and can be difficult to interpret in people with obesity and in those with kidney failure.
Certain criteria would make me more concerned that a patient is at very high risk or may already have some manifestation of HF. First is the duration of diabetes. The second consideration includes the more traditional risk factors such as smoking, hypertension (particularly if it’s poorly controlled), uncontrolled hyperglycemia for a long period of time, dyslipidemia, and of course, kidney disease and ischemic heart disease, as they are risk factors for ischemic cardiomyopathy in all patients.
If a biomarker suggests HF, I would consider ordering echocardiography. If it is abnormal, I likely would refer to cardiology. I suspect that my primary care colleagues would take a similar approach.
How SGLT2i Offer Other Opportunities for Collaboration Among Endocrinologists, Cardiologists, and Primary Care
Recent clinical trials—such as DAPA-HF and EMPEROR-Reduced—are showing us how best to treat patients with T2D and HF. Identification and treatment of patients with clear indications for SGLT2i therapy is the responsibility of essentially all healthcare professionals caring for patients with T2D and HF.
Hypoglycemia is of course a concern for anyone who treats T2D, but it may be a particular concern for cardiologists who are planning to add SGLT2i to the care of a patient receiving other medicines for glycemic control. Another concern is whether the patient’s endocrinologist or primary care professional will be upset because the cardiologist has introduced a “diabetes” drug. Cardiologists prescribe SGLT2i to improve cardiovascular and renal outcomes. However, as they increasingly prescribe SGLT2i for people with HF who do not have diabetes, their level of comfort in prescribing them to everyone will probably increase.
Cardiologists may also worry that if they start prescribing a diabetes medication, they might be perceived as being fully in charge of the patient’s glycemic management. But in 2021, there really should be no expectation that prescribing an SGLT2i to improve cardiovascular and renal outcomes means that you have bought into managing hyperglycemia entirely.
Endocrinologists are very careful physicians, and we weigh the risks and benefits of treatments thoroughly. Of interest, we know more about the safety profile of SGLT2i than we’ve known about almost any drugs for diabetes that have come before. With that should come confidence in prescribing these drugs to improve cardiovascular and kidney outcomes. For example, the risk of some adverse events of SGLT2i, such as Fournier gangrene, is very small, but it is of course an undesirable outcome. Anyone who prescribes SGLT2i must invest some time talking with the patient about that risk, and some patients who are already at high risk for that complication may simply not be good candidates for treatment. But overall, it is clear to me that the benefits of SGLT2i outweigh the risks as far as our patients’ overall health and long-term prognosis are concerned. We should not allow concern for the risk of rare adverse events to derail the implementation of effective therapy.
Using SGLT2i in Patients With T2D Who Are Hospitalized for HF
In the past, most trials of SGLT2i enrolled patients who were relatively stable and treated in the outpatient setting, but that is changing. We learned a lot from SOLOIST WHF, which compared an SGLT1/SGLT2i (sotagliflozin; not commercially available in the US) to placebo in patients hospitalized with T2D and acute HF. The primary endpoint was the number of deaths due to cardiovascular causes and hospitalizations and urgent visits for HF. Sotagliflozin vs placebo was initiated in patients with HF regardless of ejection fraction once they had stabilized (eg, no longer requiring supplemental oxygen, no longer requiring IV diuretics) while still in the hospital or very shortly after discharge. It was well tolerated and reduced the risk of the primary outcome when compared with placebo during the course of the trial.
What if somebody is admitted to the hospital with decompensated HF and he or she is already receiving an SGLT2i? Until we know more about the use of these drugs in people who are acutely ill, I would recommend holding the SGLT2i in patients with acute illness that makes them unstable and that would keep them from eating or drinking regularly. I would like to see more data on the use of SGLT2i in patients with acute decompensated HF before I would feel comfortable allowing them to continue to take their SGLT2i while they’re hospitalized. FDA-approved labeling also recommends holding SGLT2i for several days before surgery to minimize the risk of euglycemic diabetic ketoacidosis. However, SOLOIST can perhaps provide some insight into when the medications can be started or restarted in hospitalized patients.
If a patient has been hospitalized, and if starting an SGLT2i is being considered, I think that is now well within the scope of cardiology practice to do, without consulting an endocrinologist or diabetes specialist. But if the patient is on a highly complex regimen for glycemic control, with multiple medications and/or injections of insulin per day, it might be worth consulting an endocrinologist as to whether those other medicines might need to be altered when the SGLT2i is added.
In general, adherence to drug regimens prescribed in the context of a hospitalization is better than to medications deferred to the outpatient setting. Cardiologists consider hospitalization for HF an opportunity to get patients onto guideline-directed medical therapy and to really change their trajectory. Now that SGLT2i are part of guideline-directed medical therapy for HF, a hospitalization for HF may actually make it easier for patients to understand the importance of taking their SGLT2i when they go home with one.
Are you currently using biomarkers to assess for HF in your patients with T2D? Echocardiography? Answer the polling question and join the conversation by posting in the comments section.
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