SGLT-2 inhibitors and GLP-1 agonists associated with better mortality outcomes than DPP-4 inhibitors for type 2 diabetes

1. SGLT-2 or GLP-1 agonists were associated with lower mortality than DPP-4 inhibitors, placebo, or no treatment.

2. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Excess mortality and cardiovascular comorbidity is a concern in patients with type 2 diabetes. Several agents including dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and sodium-glucose cotransporter 2 (SGLT-2) inhibitors have emerged efficacious in improving diabetes control. The current study is a meta-analysis that compares the efficacy and safety profile of these drug classes. SGLT-2 inhibitors and GLP-1 agonists were associated with significantly lower all-cause mortality than control groups as well as lower mortality compared to DPP-4 inhibitors. When compared to control groups, GLP-1 agonists and SGLT-2 inhibitors also had lower cardiovascular mortality, while SGLT-2 inhibitors were also associated with lower heart failure and myocardial infarction events. GLP-1 agonists were associated with higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors or DPP-4 inhibitors.

Overall, the study suggests that SGLT-2 or GLP-1 agonists are associated with lower mortality than DPP-4 inhibitors, placebo, or no treatment. Some limitations of the study include clinical efficacy and safety evaluation by drug class instead of individual drug type and possible error introduced by participant characteristics that may affect relative efficacy for each drug class. The study also does not address the effect of the treatments on HbA1c and glycemic control. Future directions may include comparison against commonly prescribed metformin monotherapy.

Click to read the study, published in JAMA

Relevant Reading: Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes

In-Depth [meta-analysis]: The current study is a meta-analysis that utilized a systematic search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). Eligible trials (criteria in article) were extracted and reviewed, and the primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, heart failure events, myocardial infarction, unstable angina, and stroke. Safety end points were any adverse events, hypoglycemia, as well as additional drug-class specific adverse events. Overall, 236 trials were analyzed that randomized 176,310 participants. SGLT-2 inhibitors (-1.0% absolute risk difference) and GLP-1 agonists (absolute RD -0.6%) were associated with significantly lower all-cause mortality than control groups. SGLT-2 (absolute RD -0.9%) and GLP-1 agonists (absolute RD, -0.5%) also had lower mortality compared to DPP-4 inhibitors. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment. When compared to control groups, SGLT-2 inhibitors (absolute RD, -0.8%) and GLP-1 agonists (absolute RD, -0.5%) also had lower cardiovascular mortality, and SGLT-2 inhibitors were associated with lower heart failure (absolute RD, -1.1%) and myocardial infarction (absolute RD, -0.6%) events. GLP-1 agonists were also associated with higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%) or DPP-4 inhibitors (absolute RD, 3.1%).

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