Revised: February 19, 2026
Accepted: May 6, 2026
Published online: June 26, 2026
Processing time: 140 Days and 6.5 Hours
Sodium-glucose co-transporter-2 inhibitors (SGLT-2Is), originally developed as anti-hyperglycemic medications, have emerged as cornerstone therapies for heart failure (HF) due to their cardioprotective effects. While their mortality benefits in HF are established, their role in patients with both HF and chronic obstructive pulmonary disease (COPD) remains unclear.
To evaluate the effects of SGLT-2Is in patients with HF with coexisting COPD, focusing on hospitalization, cardiovascular (CV) mortality, and drug-related complications.
A systematic search of PubMed and Cochrane Library databases was conducted through February 17, 2025, for randomized controlled trials assessing the safety and efficacy of SGLT-2I in HF patients with coexistent COPD. Outcomes analyzed included composite first hospitalization for HF (HHF), CV death, all-cause mortality, and time-to-first HHF. Safety endpoints included drug discontinuation, serious adverse events (AE), volume depletion, major hypoglycemia, and renal AE, reported as relative risk (RR) with 95% confidence intervals.
Four trials (n = 3224) met inclusion criteria. Of these, 1727 patients (53.6%) received SGLT-2Is, while 46.4% received placebo. Compared with placebo, SGLT-2I significantly reduced the risk of composite HHF + CV death (RR = 0.80, 95%CI: 0.70-0.91, P = 0.0006, I2 = 0%), HHF (RR = 0.77, 95%CI: 0.67-0.88, P < 0.0001, I2 = 0%), and time-to-first HHF (RR = 0.75, 95%CI: 0.57-0.99, P = 0.04, I2 = 47%). No significant differences were observed for CV death (RR = 1.01, P = 0.88) or all-cause mortality (RR = 0.94, P = 0.46). SGLT-2I did not increase risk of drug discontinuation, serious AE, renal AE, volume depletion, nor hypoglycemia.
In patients with HF and COPD, SGLT-2Is significantly reduce HF hospitalizations but do not lower all-cause mortality or CV mortality. Importantly, these drugs are well tolerated without excess AE, supporting their role as a safe therapeutic option in this population.
Core Tip: This meta-analysis evaluated the safety and efficacy of sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) in patients with congestive heart failure (HF) and coexisting chronic obstructive pulmonary disease, a population underrepresented in major HF trials. Across four randomized controlled trials, SGLT-2I significantly reduced HF hospitalizations and time-to-first hospitalization without increasing adverse events. However, no mortality benefit was observed. These findings support the safe use of SGLT-2Is to reduce hospitalization burden in this high-risk comorbid population.