Heart failure hospitalization with SGLT-2 inhibitors: a systematic review and meta-analysis of randomized controlled and observational studies

<b>Introduction</b>: Heart failure (HF) in type 2 diabetes mellitus (T2DM) poses a significant increase in mortality. Until recently, anti-diabetic drugs have not been shown to reduce hospitalization due to heart failure (hHF). While thiazolidinedione class and saxagliptin has shown a significantly increased risk, sodium-glucose linked co-transporter 2 inhibitors (SGLT-2Is) have demonstrated a significant reduction in the risk of hHF. <b>Areas covered</b>: We systematically searched the database of PubMed, Embase, ClinicalTrials.gov, and International conference presentation up to 25 December 2018 and retrieved all the studies that were conducted for ≥24 weeks and explicitly reported hHF outcome. Subsequently, we conducted the meta-analysis to study the effect of SGLT-2Is on hHF outcome in randomized controlled trials (RCTs), observational studies, and both. <b>Expert opinion</b>: The meta-analysis of RCTs (<i>N</i> = 34,322), observational studies (<i>N</i> = 15,36,339), and both (<i>N</i> = 15,70,661) demonstrated a significant decrease in hHF (OR 0.70, 0.64, 0.66, respectively, all <i>p</i> = 0.000) with SGLT-2Is compared to placebo or other anti-diabetes drugs in T2DM. A significant benefit in hHF (OR 0.68, <i>p</i> = 0.000) is also observed in patients with established HF (<i>N</i> = 3891) in sub-group meta-analysis of RCTs. Ongoing dedicated HF trials will further enlighten the merits of SGLT-2Is in patients with established heart failure (preserved or reduced) with or without T2DM.