World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease:

Diabetes and Heart Failure: What Endocrinologists Need To Know

Increasingly, diabetes specialists need to know about preventing and treating cardiovascular complications in these patients.  A panel of experts explores the urgency of creating a new paradigm for managing congestive heart failure in patients with type 2 diabetes.

While the coexistence of congestive heart failure (CHF) is increasingly common in people with diabetes, but without specific treatment guidelines to address these comorbid conditions, endocrinologists are presented with an unheeded clinical challenge that deserves heightened attention.

As if in response, these concomitant conditions were the focus of 2 presentations at the 14th annual World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease in Universal City, California.

Vivian Fonseca, MD, addressed the role of the diabetologist in managing chronic heart failure,1 and Nikolaus Marx, MD, professor of medicine and cardiology at the University Hospital Aachen, Germany, spoke about the potential of sodium-glucose co-transporter 2 (SGLT2) inhibitors to prolong the life of those with type 2 diabetes (T2D),2 citing research indicating that decreased mortality may be driven by fewer heart failure-related events.

Tackling Diabetes and Heart Failure  

In people with diabetes, heart failure (HF) is the most common cardiovascular complication with these 2 conditions sharing similar pathogenic etiologies.3 Since an increased risk of HF may be associated with some of the commonly prescribed diabetes therapies, including insulin4; and sulfonylurea, dipeptidyl peptidase-4 (DPP4) inhibitors,5 and thiazolidinedones (TZDs),6 the urgency of endocrinologists to more actively attend to this therapeutic area has become more evident.

Findings from the Framingham Heart Study,7 suggested that HF appears at twice the rate in men with diabetes and is 5 times higher in women with diabetes than those who do not have diabetes. Furthermore, risk of HF has been shown to increase with age and duration of diabetes.6

Diabetes is highly prevalent in patients who experienced HF with both preserved ejection fraction (EFPEF) and reduced ejection fraction (EFPRF) heart failure, Dr. Fonseca, professor of medicine and pharmacology, at Tulane University Health Sciences Center, in New Orleans, Louisiana, told attendees.

When a patient has both diseases, they can expect a 70 to 80% increase in mortality risk, along with higher rates of hospitalization and longer lengths of stay,2 said Dr. Fonseca.

Even though many patients have both conditions, the effects of most glucose-lowering drugs on ventricular function and heart failure have, perhaps surprisingly, not been well researched, Dr. Fonseca said, given that most patients take a combination of medications to manage multiple conditions.

What is certain, he said, is that the more poorly blood sugar is controlled, the higher the risk of heart failure; For every 1% increase in HbA1c, heart failure risk increases by 15%,2,3 he said.

How to Identify These Patients Earlier, Better

Endocrinologists should consider the presence of heart failure in their D2M patients, the earlier the better, Dr. Fonseca said. He raised the consideration of whether or not doctors should test walking ability, for instance, with the 6-minute walking test, order an echo, or refer patients to a cardiologist early.

When clinicians see their T2D patients, Dr. Fonseca further proposes that they evaluate each person for clinical symptoms of heart failure, including: shortness of breath, edema, orthopnea and fatigue.

Systolic heart failure (HFrEF) is a ''weak pump'' problem, as the heart pumping function declines and fluid backs up into the lungs. Diastolic heart failure with preserved ejection fraction (HFpEF), is a ''stiff pump'' problem, Dr. Fonseca reminded attendees. The heart muscles thicken and stiffen, leading to a back flow of fluid into the lungs.

Extensive guidelines from the American Heart Association and the American College of Cardiology7,8 advise how and when to treat various heart failure conditions.

In addition to the guidelines, endocrinologists can be aware of ongoing research focused on which anti-diabetic drugs are most appropriate for patients with type 2 diabetes and coexisting heart failure, Dr. Fonseca said. Among the studies he cited:

  • Patients treated with TZDs had a lower incidence of heart failure. In 3,956 patients, the HR of CHF was 0.69 (CI:0.060-0.079) for TZD compared to non-TZD treated patients.6
  • Similar rates of adverse cardiovascular events occurred in pioglitazone (Actos) and placebo treated patients, researchers found in the ACT NOW trial.9 It looked at 602 patients.
  • Metformin was linked with reduced mortality compared to a comparator (mostly SU), according to a meta-analysis of 9 studies and 35,000 patients. The risk ratio was 0.80 CI: 0.74-0.87).
  • Use of DPP-4 has been met with mixed results about heart failure, Dr. Fonseca said.
  • Insulin and heart failure risk studies have produced mixed results, he said. "I personally don’t think insulin increases the risk of heart failure," he said, having not seen it in his type 1 patients.

In addition, SGLT-2 inhibitors may help reduce the incidence or progression of heart failure by lowering fat oxidation, improving glucose oxidation and increasing cardiac work efficiency, Dr. Fonseca said.

SGLT2 Inhibitors: Life Prolonging, But How?

In a separate presentation at the Congress,2 Nikolaus Marx, MD, professor of medicine/cardiology at the University Hospital Aachen, focused on SGLT2 inhibitors and how they prolong the lives of those with T2D.

Results of the EMPAR-REG Outcome trial show that empagliflozin (Jardiance) reduces overall mortality in those with T2D and cardiovascular disease,10 he said. The drug reduced both cardiovascular mortality as well as hospitalization for HF.

"I think we can say that the reduced cardiovascular end point [found in studies] most likely is through the reduction in heart failure related events," Dr. Marx said. "It's pretty clear the glucose lowering does not account for the events seen.''

In offering a more likely explanation for the favorable CVD outcomes, he cited, “weight loss, lower blood pressure, and reduction in total body sodium” as factors.

Clinical Perspective 

In assessing the challenge facing endocrinologists, another speaker at the panel, Silvio Inzucchi, MD, professor of medicine/endocrinology and director of the Yale Diabetes Center, told EndocrineWeb that for diabetes and heart failure, "we just don’t have good prospective data concerning efficacy or safety for managing these patients."

Here's what Dr. Inzucchi shared with EndocrineWeb as an overview of where the evidence basis is for managing people with diabetes and heart failure:

  • "We do know that TZDs increase the risk of heart failure hospitalization, so these drugs should probably be avoided in those with impaired left ventricular function.
  • On the other hand, metformin seems safe, so long as renal function is reasonably preserved.  If possible, avoiding agents associated with hypoglycemia (insulin, sulfonylureas) is probably a good idea, since heart failure patients are predisposed to arrhythmias."
  • "As for newer agents, the GLP-1 receptor agonists appear safe, but one study (FIGHT) conducted in a HF population showed a non-significant trend towards worse outcomes in those treated with liraglutide.  
  • For the DPP-4 inhibitors, sitagliptin looked safe in the TECOS trial. There are some concerns about saxagliptin causing an increase in HFH from the SAVOR-TIMI trial. Finally, the SGLT2 inhibitors would appear to be ideal drugs in this setting, since they have a diuretic effect. Empagliflozin recently decreased HFH and also CV mortality in the EMPA-REG OUTCOME trial, suggesting an important role for at least this drug. However, only 10% of the 7000+ patients in this trial had baseline heart failure. We don’t have any data in an actual heart failure study with any SGLT2 inhibitor, and these need to be done --both to assess efficacy and safety."

Future trials, the speakers agreed, should target combination therapies aimed at treating both the diabetes and the adverse cardiovascular risk factors.

Dr. Fonseca and Dr. Inzucchi did not indicate any financial disclosures; Dr. Marx reported consulting for Amgen and others. 

Next Summary:
Diabetes In Pregnancy Elevates T2D Risk in Youth, Attention Warranted
Last updated on


SHOW MAIN MENU
SHOW SUB MENU