No benefit to SGLT2 inhibitor therapy in hospitalized COVID-19 patients

Adding sodium–glucose co-transporter-2 (SGLT2) inhibitors to usual care in the treatment of hospitalized patients with COVID-19 does not necessarily lead to improved survival, according to the results of a meta-analysis.

Pooled data from three trials showed that the rate of all-cause mortality at day 28 following treatment initiation did not significantly differ between patients who received add-on SGLT2 inhibitor and those who received usual care alone or placebo (control). A total of 351 deaths occurred among 3,025 patients in the SGLT2 inhibitor group vs 382 deaths among 3,071 patients in the control group (summary odds ratio [OR], 0.93, 95 percent confidence interval [CI], 0.79–1.08; p=0.33). [Lancet Diabetes Endocrinol 2024;doi:10.1016/S2213-8587(24)00219-5]

The numbers translated to an absolute mortality risk of 11.7 percent in the SGLT2 inhibitor group as compared with 12.4 percent in the control group. The result was consistent across trials (I²=0 percent; p=0.52 for heterogeneity), and the GRADE assessment of certainty was high.

Likewise, there was no clear evidence that administration of SGLT2 inhibitor reduced in-hospital mortality at 28 days (summary OR, 0.85, 95 percent CI, 0.60–1.22; p=0.37; two trials: I²=36 percent, p=0.21 for heterogeneity), 90-day mortality (summary OR, 0.82, 95 percent CI, 0.62–1.10; p=0.18; two trials: I²=0 percent, p=0.54 for heterogeneity), progression to acute kidney injury or death at 28 days (summary OR, 0.92, 95 percent CI, 0.79–1.06; p=0.26; three trials: I²=0 percent, p=0.40 for heterogeneity), the need for invasive mechanical ventilation at 28 days (summary OR, 0.90, 95 percent CI, 0.78–1.04; p=0.16; three trials: I²=0 percent, p=0.39 for heterogeneity), and the duration of hospital stay at 28 days (summary OR, –0.13, 95 percent CI, –0.58 to 0.32; p=0.57; three trials: I²=0 percent, p=0.66 for heterogeneity) relative to usual care alone or placebo.

“Estimated effects of SGLT2 inhibitor, compared with usual care or placebo, were consistent across predefined subgroups. Administration of SGLT2 inhibitor was safe, with rare cases of ketoacidosis (SGLT2 inhibitor group: n=7; control group: n=2), which represents a clinically acceptable risk,” the investigators noted.

A total of 73 and 93 serious adverse events (AEs) were recorded in the SGLT2 inhibitor and control groups, respectively. However, the investigators acknowledged that they were not able to perform meta-analyses for serious AEs due to differences in approach to collecting this safety outcome.

“[These] safety data [are] of clinical relevance given that patients who are likely to be on chronic SGLT2 inhibitor therapy are also at risk of adverse outcomes from COVID-19, and the prevalence of chronic SGLT2 inhibitor therapy is likely to increase in the coming years,” the investigators said.

In addition, the study also “provides indirect evidence for revisiting the notion that chronic SGLT2 inhibitor therapy must be discontinued when patients with chronic diseases (eg, heart failure, kidney disease, or type 2 diabetes) are hospitalized for acute illness,” they added.

The rationale for investigating SGLT2 inhibitor in acutely ill COVID-19 patients was grounded on the drug’s favourable effects on inflammation, oxidative stress, glycolysis, lipogenesis, endothelial function, and oxygen carrying capacity, according to the investigators. But the present evidence does not justify the routine use of SGLT2 inhibitors, despite its safety, for this population, they added. [Diabetes Obes Metab 2021;23:886-896; Diabetol Metab Syndr 2020;12:37; Inflammopharmacolog 2021;29:269-279; Nat Commun 2020;11:2127; J Clin Endocrinol Metab 2020;105:dgaa057]

The analysis included 6,096 adult patients hospitalized with COVID-19. The median age ranged from 62 to 73 years across the trials, with 39 percent of patients being women and 25 percent having type 2 diabetes at baseline.