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SGLT-2 Inhibitors Safer and More Effective Than DPP-4s For Heart

New study finds lower occurrence of heart failure in older people with type 2.

The research, led by the American insurance company Anthem Inc., focuses on the comparative effectiveness of SGLT-2 inhibitors versus DPP-4 inhibitors in heart failure and its implications for treating the elderly with a history of heart disease or complications.

In previous research, it was suggested that with treatment using an SGLT-2 such as Jardiance (empagliflozin), Forxiga (dapagliflozin), or Invokana (canagliflozin), they could cut heart failure and death.

One of the major discoveries was in a cardiac study where empagliflozin, especially, demonstrated a 38 percent risk reduction in death for patients with type 2 diabetes. Here, researchers reviewed data specifically related to the development of heart failure.

The researchers looked at heart failure outcomes in 4,899 people newly prescribed a SGLT-2 inhibitor and 9,798 people recently put on a DPP-4i between April 2013 and December 2014. Both groups were followed for approximately two years.

The findings, published in the journal Cardiovascular Diabetology, show significant reductions in heart failure admissions observed with SGLT-2 inhibitors amongst older patients at higher risk of recurrent heart failure. They also found that the heart hospitalization risk is about 32 percent lower for new users of SGLT-2 inhibitors, compared to DPP-4 medications. However, in patients younger than 65 or without history of complications, it made no difference.

Those effects fail to explain fully this reduction in heart failure readmissions. SGLT-2 inhibitors may have a unique pharmacological profile in that they affect blood flow, the nervous system, the metabolism, and the vascular system to lower risks.

The use of SGLT-2 inhibitors in type 2 diabetes has been associated with decreased vascular stiffness and improved endothelial function, for example.

Moreover, SGLT-2 inhibitors might improve the efficiency of the failing heart by encouraging a switch to an alternative fuel to generate energy, the ketone body beta-hydroxybutyrate, which increases oxygen transport – impaired during heart failure. Whether this is a productive versus a faulty adaptive fuel shift is, however, still to be determined. Overall, this study suggests that the preferred blood-sugar–lowering drug for older patients with type 2 diabetes and a history of heart failure should be SGLT-2 inhibitors.

The study is the first to report a direct comparison of SGLT2 and DPP-4 inhibitors on the risk of heart failure hospitalization. People with type 2 diabetes are at increased risk of serious health complications, and the risk of heart failure alone is four- to fivefold higher among patients with diabetes than those without the condition. Patients with diabetes also face a higher risk of recurrent heart failure, compared with people without diabetes. Food and Drug Administration guidelines recommend doctors evaluate patients for cardiovascular risk before prescribing medication to manage diabetes.

SGLT-2 inhibitors and DPP-4 inhibitors are the latest addition to the type 2 diabetes treatment arsenal and are recommended as second-line treatment after metformin. Both SGLT-2 and DPP-4 inhibitors have received attention for their effect on cardiovascular outcomes, with clinical trials finding a reduction in cardiovascular events, including heart failure admissions with empaglifozin and canagliflozin — both SGLT-2 inhibitors — compared to placebo. However, there has been very limited information on how these findings compare to patients who use other medications.

Jeff White, Anthem’s staff vice president of clinical pharmacy services added that, “this study provides further insight into the clinical benefits observed in the real-world for individuals using certain classes of medications, and the potential for reducing medical complications. Nearly two in five Americans are expected to develop type 2 diabetes during their lifetime, according to the Centers for Disease Control and Prevention, and our finding is intriguing in light of the overwhelming interest around the reduction of heart failure risks associated with SGLT-2 inhibitors to treat patients with diabetes.”

Seniors with type 2 diabetes or those with diabetic complications were less likely to be hospitalized for heart failure while taking a sodium-glucose co-transporter 2 (SGLT-2) inhibitor compared to dipeptidyl peptidase-4 (DPP4) inhibitors, another new class of oral antidiabetic drug, according to a study released in Cardiovascular Diabetology and conducted by Anthem, Inc. and HealthCore.

The HealthCore study found that the heart failure hospitalization risk is 32 percent lower for new users of SGLT-2 compared to DPP-4 medications. In most patients younger than 65 or without history of diabetic complications, there was no risk difference. The majority of the analyzed patients were younger than 65, or didn’t have complications, and there was no risk difference among those.

Practice Pearls:

  • Empagliflozin, especially, demonstrated a 38 percent risk reduction in death for patients with type 2 diabetes.
  • Canagliflozin showed a combined risk reduction of MI, CVA, and CV death by 14 percent.
  • They also found that the heart failure hospitalization risk is 32 percent lower for new users of SGLT-2 compared to DPP-4 medications.

Reference:

Gautam  CVA, et al. Cardiovasc Diabetol  (2017) 16:93 MI, DOI 10.1186/s12933-017-0575-x