Zheng SL, et al. - Using network meta-analysis, experts pursued a comparison of the efficacies of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors on mortality and cardiovascular events in patients with type 2 diabetes. Data shed light on the connection between the use of SGLT-2 inhibitors or GLP-1 agonists with lower mortality compared to DPP-4 inhibitors or placebo or no treatment. It was discovered that the use of DPP-4 inhibitors was not related to lower mortality than placebo or no treatment.

Methods

• Data was extracted from MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017.
• Participants included patients with type 2 diabetes, with a follow-up of at least 12 weeks.
• During this study, SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment.
• Data were screened by 1 investigator and extracted in duplicate by 2 investigators and a Bayesian hierarchical network meta-analysis was conducted.
• All-cause mortality served as the primary outcome.
• Secondary outcomes included cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia.

Results

• A total of 236 trials included the randomization of 176,310 participants. SGLT-2 inhibitors (absolute risk difference [RD], -1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, -0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) led to considerably lower all-cause mortality than the control groups.
• It was reported that SGLT-2 inhibitors (absolute RD, -0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) exhibited a connection with lower mortality compared to DPP-4 inhibitors.
• No notable link was disclosed between DPP-4 inhibitors with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than were the control groups.
• Findings illustrated that SGLT-2 inhibitors (absolute RD, -0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) appeared to be prominently related to lower CV mortality than were the control groups.
• Data shed light on the notable correlation between SGLT-2 inhibitors with lower rates of HF events (absolute RD, -1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, -0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) vs control groups.
• It was deduced that GLP-1 agonists were connected with a higher risk of adverse events leading to trial withdrawal compared to SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]).