Study shows early benefits of SGLT2 inhibitors in patients with heart failure

After 1 year of treatment, SGLT2 inhibitors were associated with a 32% lower risk for hospitalization due to heart failure, regardless of type 2 diabetes status, according to a new study in Annals of Internal Medicine.

Previous randomized controlled trials have established SGLT2 inhibitors as an important treatment option in patients with heart failure (HF). The class benefits extend to patients with and without diabetes.

Sheyu Li, MD, an associate professor in the department of endocrinology and metabolism at MAGIC China Center, West China Hospital and Sichuan University, and colleagues conducted a systematic review and meta-analysis to further evaluate the effects of SGLT2 inhibitors on death, hospitalization and kidney failure in patients with HF. They also investigated whether the treatment effects differed among patients with HF with preserved ejection fraction (HFpEF) vs. those with HF with reduced ejection fraction (HFrEF) and in patients with vs. without diabetes.

“Since our latest guideline suggested a prioritized use of SGLT2 inhibitors in people with type 2 diabetes and established cardiovascular diseases, our team as well as our peers are very interested in whether SGLT2 inhibitors could improve the cardiorenal outcomes in people with HF but not type 2 diabetes,” Li told Healio. “The publication of EMPEROR-Preserved triggers this research.”

The analysis included eight randomized controlled trials evaluating Farxiga (dapagliflozin, AstraZeneca), Jardiance (empagliflozin, Boehringer Ingelheim/Eli Lilly & Co.) or Invokana (canagliflozin, Janssen) in more than 15,000 participants. An exploratory sensitivity analysis included an additional randomized controlled trial of sotagliflozin (approved in the European Union as Zynquista and developed by Lexicon) in 1,222 participants.

The SGLT2 inhibitors reduced the relative risk for hospitalization due to HF by 37% (95% CI, 25-47) at 6 months, 32% (95% CI, 20-42) at 1 year, and 26% (95% CI, 10-40) at 2 years, according to the researchers. They rated these estimates as high-certainty evidence based on the Grading of Recommendations Assessment, Development and Evaluation, or GRADE, framework.

In addition, Li and colleagues reported that SGLT2 inhibitors reduced the relative risk for cardiovascular death by 14% (95% CI, 1-25) at 1 year (high-certainty evidence). However, they did not identify a significant benefit for all-cause mortality, kidney disease progression or kidney failure (low-certainty evidence).

The anticipated absolute benefits of SGLT2 inhibitors were greater for patients with poorer prognoses, such as those newly diagnosed with HF during hospitalization, according to the researchers.

Using baseline risks, they estimated that for every 1,000 patients, 1 year of treatment with SGLT2 inhibitors would have prevented:

• 105 (95% CI, 66-138) hospitalizations among those newly diagnosed with HF in the hospital;
• 39 (95% CI, 25-52) hospitalizations among those newly diagnosed with HF in the community;
• 45 (95% CI, 28-69) hospitalizations among those previously diagnosed with HF in the hospital;
• 21 (95% CI, 13,27) hospitalizations among those previously diagnosed with HF in the community;
• 23 (95% CI, 2-41) cardiovascular deaths among those newly diagnosed with HF in the hospital; and
• 16 (95% CI, 1-29) cardiovascular deaths among those newly diagnosed with HF in the community.

The researchers also found that SGLT2 inhibitors more than doubled the risk for genital infections (RR = 2.69; 95% CI, 1.61-4.52). They estimated that treatment with SGLT2 inhibitors would lead to eight (95% CI, 3-18) more genital infections after 1 year and 17 (95 CI, 6-35) more genital infections after 2 years.

In subgroup analyses, there were no significant differences in treatment effects between patients with HFpEF vs. HFrEF and those with vs. without diabetes.

“People living with HF regardless of the presence of type 2 diabetes will receive early benefits by reducing hospitalization due to HF from SGLT2 inhibitors, especially those in severe conditions and within a 1-year treatment,” Li said. “The long-term effectiveness and safety of SGLT2 inhibitors, as well as their termination after 1 year of treatment, warrant further investigations in people living with HF.”