1. SGLT2 INHIBITORS REDUCE RISK OF HEART FAILURE IN TYPE 2 DIABETICS: A META-ANALYSIS
Tariq Jamal Siddiqi1; Muhammad Shariq Usman1; Fahad Khan1; Nawaz Lashari1;
1Dow University of Health Sciences, Karachi, Pakistan
Results
Introduction
Type 2 diabetes mellitus (T2DM) is associated with considerably increased risk of heart failure. Sodium glucose co-transporters 2 (SGLT2) inhibitors have emerged as a new class of anti-diabetic medication known to have favourable effects on biomarkers, including glycaemia, blood pressure and weight. Protection against cardiovascular events has also been reported, but without conclusive evidence. We conducted a meta-analysis of all available data to evaluate the effects of SGLT2 inhibitors on heart failure in T2DM patients. 
This analysis included 14 randomized controlled trials (4 of canagliflozin, 3 of empagliflozin, 7 of dapagliflozin).
In these studies, a total of 25,043 patients were randomized to either the SGLT2 arm (n=15,703) or the placebo arm (n=9340).
SGLT2 inhibitors significantly reduced the risk of heart failure (OR: 0.67; 95% CI: ; p < 0.001) .This significant effect was strongly driven by the evidence present for the Empagliflozin drug.
There was no difference in effect between the canagliflozin, empagliflozin and dapagliflozin subgroups (p=0.94)
Figure 2: Funnel plot indicated no small study or publication bias.
Possible Mechanisms
The strong benefit of SGLT2 inhibitors on heart failure cannot be explained simply by the reduction in glycaemic levels.
Inhibitory effect of SGLT2 inhibitors on the sodium hydrogen exchanger 3 (NHE3) in both the kidney and heart may be responsible for the reduction in the risk of heart failure.
In the kidney, the NHE3 inhibition could lead to increased sensitivity to diuretics and natriuretic peptides, leading to decreased preload in heart failure patients.
In cardiac tissue, NHE3 inhibition could lead to reduced cardiac injury, systolic dysfunction and hypertrophy
Methods
We queried the MEDLINE, SCOPUS, and clinicaltrials.gov databases to identify published and unpublished clinical trials that compared SGLT2 inhibitors to placebos.
Only those trials were selected which reported heart failure incidence or worsening, and had a follow up of at least 24 weeks.
Subgroup analysis of individual drugs within the SGLT2 class was also performed.
RevMan 5.3 was used to pool the results of all studies, using a random-effects model.
Conclusions
This comprehensive meta-analysis provides strong evidence for reduced risk of heart failure in T2DM patients taking SGLT2 inhibitors. Currently, heart failure patients with co-existent T2DM should preferably be switched to a regime which includes SGLT2 inhibitors.
Figure 1: Forest Plot comparing incidence or worsening of heart failure between SGLT2 inhibitor and placebo groups
Contact
References
Tariq Jamal Siddiqi
Dow Medical College, DUHS
Phone: