As a class, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have consistently demonstrated benefit—initially as a treatment for type 2 diabetes, and eventually as a class of drugs that can also protect the heart and kidneys in persons with or without diabetes. Consider this list of what have been characterized as practice-changing trials: EMPA-REG, DAPA-HF, EMPEROR-Reduced, DEFINE-HF, DECLARE-TIMI 58, or this meta-analysis trial findings, all of which confirm impressive benefits, and little risk, for treatment with an SGLT2i.
The takeaways?
- Empagliflozin clearly reduces all-cause and cardiovascular (CV) mortality in patients with existing atherosclerotic cardiovascular disease (ASCVD) (RRR 32%).
- All SGLT2i reduce the risk of major adverse CV events (composite of CV death/MI/stroke) in patients with existing ASCVD (RRR 14%).
- SGLT2i neither increase nor reduce stroke risk.
- All SGLT2i reduce the risk of HF hospitalization (RRR ~30%).
Against that background, the possibility that SGLT2i treatment might prove beneficial to persons hospitalized with Covid-19 had an appealing logic, explained Mikhail Kosiborod, MD, vice-president for research at Kansas City, Missouri’s Saint Luke’s Health System and a cardiologist at St. Luke’s Mid America Heart Institute.
Kosiborod presented findings from the DARE-19 trial during a late-breaking clinical trial session at ACC.21, the American College of Cardiology’s virtual meeting.
“We already know that SGLT2i provide organ protection in patients with type 2 diabetes, heart failure and chronic kidney disease, and these are the exact same patients who—if they contract Covid-19—are at high risk to be hospitalized with serious illness and develop complications, such as organ failure.”
The randomized, placebo-controlled trial enrolled 1,250 hospitalized Covid-19 patients at 95 sites in the U.S., Brazil, Mexico, Argentina, India, Canada, and the U.K. between April 2020 and January 2021. In addition to having confirmed SARS-CoV-2 infection, the patients had hypertension, diabetes, atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease.
The mean age of patients was 61 in the dapagliflozin arm and 62 in the control group. More than 40% of patients were women and half of the patients had type 2 diabetes. More than a third of the patients were taking an ACE inhibitor or an angiotensin receptor blocker at baseline. Eighteen percent of patients received remdesivir therapy.
They were evenly randomized to dapagliflozin (10 mg) or placebo daily for 30 days, with treatment starting within four days of hospital admission.
“These were patients who were at high risk for severe Covid-19 disease, so treatment was started when they were on general medical floors but was continued for patients who were transferred to ICU beds,” said Kosiborod during a press conference. The treatment continued for 30 days, and follow-up was planned for 60 and 90 days after last dose.
Numerically, there were fewer deaths in the dapagliflozin group than in the placebo arm, “but the difference was not statistically significant,” he said.
Among the findings:
- There were 88 events (organ failure or death) in the placebo arm (13.8%) and 70 in the dapagliflozin arm (11.2%) (HR 0.89; 95% CI 0.58-1.10; P=0.168).
- All endpoint components numerically favored dapagliflozin: all-cause mortality 41 versus 54; kidney decompensation 24 versus 35; cardiac decompensation 47 versus 58; respiratory decompensation 58 versus 70; and new or worsening organ dysfunction 64 versus 80.
Kosiborod said that from a clinical standpoint, the findings suggest that patients who are on SGLT2i treatment should be maintained on therapy if hospitalized with Covid-19.
“There were concerns at the beginning of the pandemic about the safety of SGLT2i in patients hospitalized with Covid-19, and some groups were recommending discontinuation of these medications in this setting, even in individuals with chronic conditions known to benefit from these drugs,” he said. “Our findings show that dapagliflozin is well-tolerated in patients hospitalized with Covid-19, with no new safety issues being observed. This should have implications for clinical practice given that our results do not support discontinuation of SGLT2i in this setting, as long as patients are monitored.”
Additionally, the findings suggest that “SGLT2i may provide organ protection in acute illness. This should inform future clinical science and hopefully lead to further investigations.”
Asked what hospitalized patients might benefit from SGLT2i treatment, he told BreakingMED that in “an illness like sepsis, for example, there is at least theoretically the possibility of benefit. Now, you would need to do larger trials with larger numbers of events to prove it, but this study does certainly raise the possibility.”
- Be aware that the findings from the DARE-19 trial suggest that patients on SGLT2i therapy can continue treatment while hospitalized with Covid-19.
- Note that in a randomized trial of high risk patients hospitalized for Covid-19, SGLT2i treatment was associated with numerically fewer cases of organ decompensation, but the difference did not reach statistical significance.
Peggy Peck, Editor-in-Chief, BreakingMED™
The DARE-19 trial was funded by AstraZeneca.
Kosiborod disclosed grant support from AstraZeneca and Boehringer Ingelheim, as well as consultant or clinical trial leadership agreements with AstraZeneca, Applied Therapeutics, Amgen, Bayer, Boehringer-Ingelheim, Eli Lilly, Janssen, Merck (Diabetes) Novo Nordisk, Sanofi, and Vifor Pharma.
Cat ID: 103
Topic ID: 74,103,730,103,3,305,446,12,13,187,307,127,411,192,669,927,918,925,934,168
