Two classes of drugs developed for patients with type two diabetes mellitus (T2DM) are finding increasing use as beneficial formulations for the treatment of patients with cardiovascular (CV) disease. Another class of the drugs has become particularly important in treatment of patients at risk of heart failure (HF).
Robert J. Mentz, MD, a Duke HF specialist and researcher, points to clinical evidence in recent studies of drugs developed to treat T2DM that are contributing to improved outcomes among patients with CV disease at risk for HF, specifically:
- DPP-4 inhibitors have been determined to be non-inferior for major adverse cardiac events (MACE) compared with placebo, but several medications in the class appear to increase HF hospitalizations (e.g., saxagliptin and alogliptin).
- GLP-1RAs reduced MACE and mortality in several studies but overall do not appear to have significant effects on HF.
- SGLT2 inhibitors reduced HF-related hospitalizations as well as MACE.
“The use of SGLT2-inhibitors, which were developed for diabetes but also have an effect on HF, is an important observation that has not been on every clinician’s radar,” Mentz says. “But the studies in patients with diabetes are consistent and clear with regard to the benefits of SGLT2-inhibitors. Ongoing studies are exploring their use specifically in HF both with and without comorbid T2DM. Now we need to begin to fully understand the benefits, the risks, and the most effective methods to incorporate these medications into clinical practice.”
To fully leverage the benefits of these drugs, Mentz, who has studied the links between T2DM and HF, urges collaboration among endocrinologists, cardiologists, and primary care physicians to help patients with diabetes and underlying CV diseases, including HF.
The Endocrinology Perspective
Duke endocrinologist Jennifer B. Green, MD, whose research focuses on cardiovascular outcomes trials in diabetes and who collaborates with Mentz, says many patients with T2DM or advanced cardiovascular disease who are relatively stable may not see an endocrinologist regularly.
“That’s why is it so important that all caregivers of patients with diabetes who have high cardiovascular risk be aware of the benefits of these new medications,” Green says. “We need to be more diligent about communicating these options and ensuring that all providers are engaged.”
Green is among the researchers participating in a Duke Clinical Research Institute trial focused on optimizing care for patients with diabetes and cardiovascular disease. The COORDINATE-Diabetes project will assess implementation of guideline-recommended therapies, including use of these beneficial diabetes medications in cardiology clinics throughout the US.
The interaction between T2DM and HF, Mentz says, is a two-way pathophysiologic link. Arteriosclerosis, coronary artery disease, and cardiomyopathy are associated with hyperglycemia and insulin resistance. These factors limit energy efficiency and anabolic function and lead to endothelium dysfunction, which can lead to or worsen chronic heart failure. Patients with T2DM are much more likely to experience HF.
“We are acquiring a growing understanding about the science and the clinical implications of both conditions,” Mentz says. “The landscape has changed a great deal in recent years. Five years ago, we were not aware of the benefits these diabetes drugs offer patients with cardiovascular disease, including HF.”
Cardiologists and endocrinologists have aligned interests in the use of T2DM drugs for heart conditions, Mentz says, but slightly different perspectives. “It’s an exciting time to discover the ways in which these therapies can help our patients,” he says. “From looking at the clinical benefits observed in clinical trials and real-world evidence as well as the patient experience following their initiation, we can become better informed on how incorporate them more effectively into daily use.”
In the United States, more than 6 million individuals have HF and the condition is the number one reason for hospital admissions. For patients covered by Medicare, HF is the single largest cause of hospital admissions.
Despite a number of new medications, about 50% of patients with HF die within five years. “The condition has a mortality rate that is as bad or worse than most cancers,” Mentz says. “HF doesn’t get the attention of diseases such as cancer as a contributor to mortality, but the disease creates a significant decline in the survival and quality of life for patients.”
The application of these diabetes medications coupled with improved use of other guideline-directed therapies specifically developed for HF may contribute to better outcomes for patients with HF, Mentz says. “But we need to learn a lot more about what we can do for these patients to help use the right medications at the right doses to optimize patient outcomes.”