Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.
Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.
The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.
The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.
“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
Just a beginning step, although trial probably wasn’t long enough
However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”
Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”
Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.
In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.
He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.
“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”
The duration of follow-up in the current study is also a limitation, he added.
“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”
Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”
He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.
“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.