A CME Journal For Family Physicians


Which Type 2 Diabetes Treatments Best Reduce Mortality?

The use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors or glucagon-like peptide 1 (GLP-1) agonists is tied to lower rates of mortality compared with dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with type 2 diabetes, according to new findings.
Researchers arrived at this conclusion following a network meta-analysis of 236 trials comprised of 176,310 participants with type 2 diabetes.
Each trial included in the analysis had compared SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors with each other, with placebo, or with no treatment, and included at least 12 weeks of follow-up.
Specifically, the researchers examined the primary outcome of all-cause mortality, and secondary outcomes of cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke. Safety end points included adverse events and hypoglycemia.
Results indicated that SGLT-2 inhibitors (hazard ratio [HR] 0.80) and GLP-1 agonists (HR 0.88), were associated with significantly lower all-cause mortality compared with control groups.
In addition, both SGLT-2 inhibitors (HR 0.78) and GLP-1 agonists (HR 0.86) were associated with lower mortality compared with DPP-4 inhibitors, whereas DPP-4 inhibitors were not significantly associated with lower all-cause mortality compared with control groups (HR 1.02).
For CV mortality, SGLT-2 inhibitors (HR 0.79) and GLP-1 agonists (HR 0.85) demonstrated lower mortality rates vs control groups. Furthermore, SGLT-2 inhibitors were strongly associated with lower rates of HF events (HR 0.62) and MI (HR 0.86) compared with controls
However, the researchers noted that GLP-1 agonist use often demonstrated a higher risk of adverse events leading to trial withdrawal compared with SGLT-2 inhibitors (HR 1.80) and DPP-4 inhibitors (HR 1.93).

Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA. 2018;319(15):1580-1591.