Cardiovascular and renal safety of metformin in patients with diabetes and moderate or severe chronic kidney disease: Observations from the EXSCEL and SAVOR-TIMI 53 cardiovascular outcomes trials.

Abstract

AIM:

To provide evidence on the cardiovascular and renal safety of metformin in chronic kidney disease (CKD) stages 3 to 4.

MATERIALS AND METHODS:

This post hoc analysis compared participants with an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73m2 in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) and the Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (SAVOR-TIMI 53) trials taking metformin, with those not exposed to metformin during these trials, using a propensity-matching approach. Adjusted Cox proportional hazards models were used to assess risk of major adverse cardiovascular events (MACE) and all-cause mortality (ACM). Metformin effect on eGFR slope was calculated using a mixed-model repeated measures analysis, and the number of lactic acidosis events was tabulated.

RESULTS:

No strong trend for lower metformin doses with lower eGFR values was observed in either the EXSCEL or SAVOR-TIMI 53 trials. In the 1745 metformin-using participants matched to non-metformin users, metformin had neutral effects on MACE (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.76-1.08; P = 0.28) and ACM (HR 0.86, 95% CI 0.70-1.07; P = 0.18), with no interaction by CKD stage, or with use of exenatide or saxagliptin. An improvement in eGFR slope was observed with metformin in the CKD stage 3B cohort in SAVOR-TIMI 53, but not in other groups.

CONCLUSIONS:

This analysis of participants with CKD stages 3 to 4 from two cardiovascular outcomes trials supports the cardiorenal safety of metformin, but does not suggest a consistent benefit on MACE, ACM, or eGFR slope across this population.

• Authors: Lindsay E Clegg, Yankang Jing, Robert C Penland, David W Boulton, Adrian F Hernandez, Rury R Holman, Jiten Vora
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 23 Issue 5 Pg. 1101-1110 (05 2021) ISSN: 1463-1326 [Electronic] England
• PMID: 33394543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 John Wiley & Sons Ltd.

Chemical References

• Metformin

Topics

• Cardiovascular Diseases (epidemiology, prevention & control)
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Glomerular Filtration Rate
• Humans
• Kidney
• Metformin (adverse effects)
• Renal Insufficiency, Chronic (complications, epidemiology)