Results. Compared with the patients in the control groups (placebo or no treatment), patients in both the SGLT-2 inhibitor and GLP-1 agonist groups had decreased all-cause mortality (SGLT-2 inhibitor group, hazard ratio [HR]=0.80; 95% credible interval [CrI], 0.71-0.89; absolute risk difference [RD]= –1%; number needed to treat [NNT]=100; GLP-1 agonist group, HR=0.88; 95% CrI, 0.81-0.94; absolute RD= -0.6%; NNT=167). Patients in the DPP-4 inhibitor group did not have a difference in mortality compared with the control groups (HR=1.02; 95% CrI, 0.94-1.11; absolute RD=0.1%). Both the SGLT-2 inhibitor (HR=0.78; 95% CrI, 0.68-0.90; absolute RD= –0.9%; NNT=111) and GLP-1 agonist (HR=0.86; 95% CrI, 0.77-0.96; absolute RD= –0.5%; NNT=200) groups had reduced all-cause mortality when compared with the DPP-4 inhibitor group.
CV endpoints. Similarly, the SGLT-2 inhibitor (HR=0.79; 95% Crl, 0.69-0.91; absolute RD= –0.8%; NNT=125) and GLP-1 agonist (HR=0.85; Crl, 95% 0.77-0.94; absolute RD= –0.5%; NNT=200) groups had a reduction in CV mortality compared with the control groups, while those in the DPP-4 inhibitor group experienced no effect. Additionally, those taking SGLT-2 inhibitors had lower rates of HF events (HR=0.62; 95% CrI, 0.54-0.72; absolute RD= –1.1%; NNT=91) and MIs (HR=0.86; 95% CrI, 0.77–0.97; absolute RD= –0.6%; NNT=167) than those in the control groups. They also had lower rates of HF than those taking GLP-1 agonists (HR=0.67; 95% CrI, 0.57 to 0.80; absolute RD= –0.9; NNT=111) or DPP-4 inhibitors (HR=0.55; 95% CrI, 0.46-0.67; absolute RD= –1.1%; NNT=91). Neither the GLP-1 agonist groups nor the DPP-4 inhibitor groups saw lower rates of HF or MI than the control groups.
Adverse effects. DPP-4 inhibitors, GLP-1 agonists, and SGLT-2 inhibitors were all associated with a small increased risk for hypoglycemia compared with the control groups, but there were no significant differences between drug classes. All agents resulted in an increased risk for adverse events leading to trial withdrawal compared with the control groups (GPL-1 agonists, HR=2; 95% CrI, 1.70-2.37; absolute RD=4.7%; number needed to harm [NNH]=21; SGLT-2 inhibitors, HR=1.8; 95% CrI, 1.44-2.25; absolute RD=5.8%; NNH=17; and DPP-4 inhibitors, HR=1.93; 95% CrI, 1.59-2.35; absolute RD=3.1%; NNH=32).
When compared with the control groups, the SGLT-2 inhibitor group was associated with an increased risk for genital infection (relative risk [RR]=4.19; 95% confidence interval [CI], 3.45-5.09; absolute RD=6%; NNH=16), but not of urinary tract infection or lower limb amputation, although the authors noted high heterogeneity among studies with regard to the limb amputation outcome. DPP-4 inhibitors were associated with an increased risk for acute pancreatitis (RR=1.58; 95% CI, 1.04-2.39; absolute RD=0.1%; NNH=1000) compared with control groups.
WHAT’S NEW
SGLT-2s: Lower mortality, fewer heart failure events
This meta-analysis concludes that when compared with placebo or no treatment, the use of SGLT-2 inhibitors or GLP-1 agonists is associated with lower all-cause mortality and lower CV mortality than is the use of DPP-4 inhibitors. Additionally, SGLT-2 inhibitors are associated with lower rates of HF events than GLP-1 agonists or DPP-4 inhibitors.
Continue to: CAVEATS
