Studies Show Cardiovascular Benefit With Sotagliflozin

For patients with type 2 diabetes and chronic kidney disease, treatment with the diabetes drug sotagliflozin produced a 26% reduction in key cardiovascular events, including heart failure, according to results from the SCORED study released Monday.

Meanwhile, the drug significantly cut the risk of cardiovascular death and lowered the burden of treatment for heart failure by 33%, according to findings from the SOLOIST-WHF trial, also released Monday at the American Heart Association Scientific Sessions meeting.

Both studies were published online by The New England Journal of Medicine.

Sotagliflozin is part of a class of drugs known as sodium-glucose cotransporter 2 (SGLT2) inhibitors.

On top of prior studies of SGLT2 inhibitors, the two new ones "show the data are overwhelming that the majority of patients with diabetes who have heart failure or chronic kidney disease, barring a complication, should be an SGLT2 inhibitor" regardless of brand, Dr. Deepak Bhatt of Brigham and Women's Hospital in Boston told Reuters Health in a telephone interview. Dr. Bhatt was the chief author of both studies.

Both trials ended prematurely because funding from Lexicon Pharmaceuticals dried up when investors panicked during the early days of the COVID-19 pandemic. The drug is sold under the brand name Zynquista in Europe.

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"We were fortunate that the drug effects were so strong, we were able to see the effects quickly, even though the duration of the study was much shorter than we planned," said Dr. Bhatt. "Had it not been the case, we might have missed a smaller benefit that still would have been clinically important."

In the larger SCORED trial, which enrolled 10,584 volunteers with type 2 diabetes, chronic kidney disease and an elevated risk for cardiovascular disease, the odds of reaching the primary endpoint of death from cardiovascular causes, hospitalization for heart failure or the need for an urgent visit for heart failure were 5.6% per year with sotagliflozin versus 7.5% with placebo (P<0.001).

The percentages were based on a median exposure to sotagliflozin of 14.2 months.

"We see benefits occur pretty early, within three months," said Dr. Bhatt, director of the hospital's interventional cardiovascular program. He also noted that, unlike some other studies, this one included patients with or without albuminuria.

For a combination of death from cardiovascular causes, heart attack or stroke, sotagliflozin lowered the risk by 16% (hazard ratio of 0.85 with a 95% confidence interval of 0.72 to 0.99). For a combination of death from a cardiovascular cause or hospitalization for heart failure, the drug lowered the risk by 23% (hazard ratio of 0.77 with a confidence interval of 0.66 to 0.91).

However, when the Bhatt team focused on deaths from cardiovascular causes, the difference in the two groups was not significant, with a yearly rate of 2.2% for the drug and 2.4% for placebo. The rates of death from any cause were identical in the two groups.

If the trial had continued, a mortality benefit might have surfaced, Dr. Bhatt said.

Diarrhea affected 8.5% of sotagliflozin patients (42% more than placebo patients), volume depletion was seen in 5.3% (33% more), genital mycotic infection occurred in 2.4% (making it 2.7 times more common than in the placebo group) and diabetic ketoacidosis was twice as common with the drug, occurring in 0.6% of those patients.

The SOLOIST-WHF trial followed 1,222 volunteers with type 2 diabetes who had been recently hospitalized for worsening heart failure.

After a median follow-up of nine months, the Bhatt team calculated that in the intervention group, 51.0% of patients per year were hospitalized or had an urgent visit for heart failure or died from cardiovascular causes. The rate was 76.3% among placebo recipients (P<0.001).

The biggest improvement was in the subcategory of hospitalizations or urgent visits for heart failure. Those outcomes occurred at a rate of 40.4% per year with sotagliflozin versus 63.9% with placebo (P<0.001).

The improvement in the cardiovascular death rate alone was less dramatic and not statistically significant. It was 10.6% with sotagliflozin and 12.5% without, a 16% reduction but with a confidence interval of 0.58 to 1.22. The odds of death from any cause were similar.

The drug was given during hospitalization or shortly after discharge and the benefit surfaced so quickly — producing fewer heart attacks and strokes after just three months — that doctors shouldn't be waiting to give it, said Dr. Bhatt. "If the patient is eligible for it, you don't want to wait six months until you see them again because you could have prevented some cardiovascular events."

Once again, diarrhea was a common and expected side effect. The rates of severe hypoglycemia were 1.5% among sotagliflozin recipients and 0.3% with placebo.

The treatment also produced "a pretty substantial improvement" in a patient's quality of life, the researcher said. "They might expect not only to stay out of the hospital from exacerbations but also to feel better when they are home."

Sotagliflozin therapy did not produce significantly higher rates of hypotension or acute kidney injury.

—Gene Emery

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