SGLT2 inhibitors may lower risk for HF in patients with type 2 diabetes

WASHINGTON — Sodium-glucose co-transporter 2 inhibitors were linked to decreased risk for hospitalization for HF and death, according to findings presented at the American College of Cardiology Scientific Session.

“If you look at the clinical trial data, [HF] is actually one of the most common [CVD] complications of type 2 diabetes,”

Mikhail Kosiborod, MD, professor of medicine at Saint Luke’s Mid America Heart Institute and University of Missouri-Kansas City School of Medicine, said in an interview with Cardiology Today. “Not only that, but it’s arguably the most morbid of [CV] complications of type 2 diabetes, because the survival of patients with type 2 diabetes who develop new [HF] is extremely poor.

“If the goals of managing diabetes are to prolong life and improve the quality of life, one of the best ways of doing that is actually preventing [HF] or developing better ways of treating [HF] in patients with type 2 diabetes,” Kosiborod told Cardiology Today. “[HF] is extremely important if you really want to impact survival in this patient group.”

Kosiborod explained that in previous clinical trials that analyzed intensive glucose-lowering as a treatment strategy, there was no benefit for all-cause death or HF. Several classes of glucose-lowering drugs had possible safety issues regarding HF. “Here comes an opportunity now with one of the novel classes of glucose-lowering drugs — specifically SGLT2 inhibitors, because of the mechanism of action, and it’s actually a possibility that you could have a class of medications that would not only be safe to treat diabetes with in patients with [HF], but could actually either prevent [HF] or improve [HF] management,” Kosiborod told Cardiology Today.

CVD-REAL was an observational, retrospective cohort study in which researchers analyzed data from 309,056 patients from six countries older than 18 years with established type 2 diabetes who were new users of either SGLT-2 inhibitors or other glucose-lowering drugs. The majority of the cohort (87%) did not have established CVD. Those taking SGLT2 inhibitors (n = 154,523; mean age: 57; 44% women) were compared with those taking other glucose-lowering drugs (n = 154,523; mean age: 57; 45% women).

The primary outcome was hospitalization for HF. Secondary outcomes included all-cause death and the combination of all-cause death and hospitalization for HF.

In the first cohort, which included all of the countries from the study, specific SGLT2 inhibitor contributions in terms of total exposure time were as follows: canagliflozin (Invokana, Janssen Pharmaceuticals; 52.7%), dapagliflozin (Farxiga, AstraZeneca; 41.8%) and empagliflozin (Jardiance, Boehringer Ingelheim; 5.5%). The second cohort, which did not include Germany, in which all-cause mortality data were unavailable, had similar percentages of use (42.3%, 51% and 6.7%, respectively).

Treatment with SGLT2 inhibitors was associated with a 39% relative risk reduction in hospitalizations for HF compared with other glucose-lowering drugs (HR = 0.61, 95% CI, 0.51-0.73). The results were consistent throughout all of the countries. “In all three sensitivity analyses, the results were highly stable and continued to show consistent reduction in the risk of hospitalization for [HF] with SGLT2 inhibitors vs. other glucose-lowering drugs,” Kosiborod said.

A 51% relative risk reduction in all-cause death was noted in patients treated with SGLT2 inhibitors vs. other glucose-lowering medications (HR = 0.49; 95% CI, 0.41-0.57). For the composite of hospitalizations for HF and all-cause death, patients treated with SGLT2 inhibitors had a 46% relative risk reduction (HR = 0.54; 95% CI, 0.48-0.6).

“We did not see any significant heterogeneity across countries, despite geographic variations in use of specific SGLT2 inhibitor compounds, with predominance of canagliflozin in the United States and dapagliflozin in Europe,” Kosiborod said. “Therefore, the observed [CV] benefits appear to be class-related. Second, we looked at the broad population of patients with type 2 diabetes in general practice, the overwhelming majority of whom, nearly 90%, did not have established [CVD], which suggest that the benefits may extend to those at the lower end of the risk spectrum. And finally, for all of the outcomes, including hospitalization for [HF] and death, the point estimates that we observed were remarkably similar to those seen in EMPA-REG Outcome trial, which appears to suggest that the benefits may translate to real-world clinical practice.”

“To examine whether it was the beneficial effect associated with SGLT2 inhibitors … or potential harm from other glucose-lowering medication classes, we did a sensitivity analysis, in which we sequentially removed certain classes of glucose-lowering medications from the comparative group,” Kosiborod said to Cardiology Today. “This did not change the results at all, suggesting that what we are observing is likely the benefit of SGLT2 inhibitors.” – by Darlene Dobkowski and Katie Kalvaitis

Reference:

Kosiborod M, et al. Featured Clinical Research III. Presented at: American College of Cardiology Scientific Session; March 17-19, 2017; Washington, D.C.

Disclosure: The study was funded by AstraZeneca. Kosiborod reports receiving consultant fees or honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Glytec, Merck, Novo Nordisk, Sanofi Aventis and ZS Pharma; receiving research grants from AstraZeneca Pharmaceuticals, Boehringer Ingelheim, Gilead and Sanofi Aventis; and speaking for Amgen.