Analysis: Metformin Lowers All-cause Death in Type 2 Diabetics

Metformin was associated with a reduction in all-cause mortality, but not a composite study endpoint, in high-risk patients with type 2 diabetes mellitus, a post-hoc analysis suggests.

The Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (SAVOR-TIMI 53) study, whose results were previously published in 2013, included 12,156 patients with type 2 diabetes who were classified as eitehr taking or never taking metformin. The researchers for SAVOR-TIMI 53 used inverse probability of treatment weighting Cox modeling to obtain a composite endpoint of cardiovascular death, myocardial infarction (MI), or ischemic stroke. Additional endpoints included all-cause mortality and cardiovascular death, as well as biomarkers included as covariates.

There was a total of 937 composite outcomes events, 407 cardiovascular deaths, and 600 all-cause deaths during the study period, with a median follow-up of 2.1 years. According to the analysis, of the 12,156 patients with baseline biomarker samples, most (74%; n=8,971) had metformin exposure, 13% (n=1,611) had prior heart failure, and 11% (n=1,332) had moderate chronic kidney disease. There was no reported difference for the composite study endpoint with metformin use (HR for inverse probability of treatment weighting=0.92; 95% CI, 0.76-1.11). However, there was a reduction in all-cause mortality (HR for inverse probability of treatment weighting=0.75; 95% CI, 0.59 to 0.95). The analysis authors reported no relationship between metformin use and the study endpoints in the patients with prior heart failure and severe chronic kidney disease.

“Taken together, the findings presented here show a strong association between metformin exposure and lower rates of all-cause mortality in patients with type 2 diabetes mellitus and elevated cardiovascular risk,” the researchers wrote.

They concluded by emphasizing that they took extra steps to reduce confounding in the data.

“Using extensive statistical techniques to adjust and match for comorbidities, patient characteristics, baseline biomarkers, and propensity for metformin exposure, we found that in patients with type 2 diabetes mellitus and high cardiovascular risk, metformin use was associated with lower rates of all-cause mortality but not with lower rates of the composite end point of cardiovascular death, MI, or ischemic stroke,” they concluded. “This association was most apparent in those patients without prior heart failure or moderate to severe chronic kidney disease. These findings emphasize the need for an adequately powered randomized trial in these high-risk patients.”

Promising data for #metformin:
⬇️ all-cause mortality for people with #diabetes and ⬆️ #cardiovascular risk

(caveat: effect less in HF & mod-severe CKD). #CardioTwitter #endotwitter https://t.co/Zrq4J7W3uG

— Rachel Pessah-Pollack, M.D., F.A.C.E. (@DrPess) September 19, 2019

http://twitter.com/ten0v/statuses/1174401148268294144

#metformin use was associated with lower rates of all-cause mortality, including after adjustment for clinical variables and biomarkers, but not lower rates of the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. https://t.co/PLzLE7vqJL

— PABLO MOROCHO RIOFRIO MD (@PabloMorochoRMD) September 17, 2019

In post hoc analysis of SAVOR-TIMI 53, metformin associated w/ (down arrow) all-cause mortality, but not MACE. However, effect not seen in pts w/ HF or mod-sev CKD. https://t.co/Zz8Tva9oqM #AHAJournals @BrianBergmark @TIMIStudyGroup @BrighamWomens @BrighamResearch @DLBhattD pic.twitter.com/Iawd4zLQms

— Circulation (@CircAHA) September 18, 2019