Metformin and Cardiovascular Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease
Diabetes mellitus is a serious chronic disease that, due to its ever-increasing prevalence, poses a significant problem for society in developed countries. The main cause of morbidity and mortality in patients with type 2 diabetes is cardiovascular disease, and the likelihood of their occurrence is increased by concomitant chronic kidney disease. In current diabetes treatment, antidiabetic agents are thus preferred, as they also provide cardioprotective and nephroprotective effects.
Metformin, the first-line drug for type 2 diabetes, has a proven effect on reducing cardiovascular risk, but it is not used in diabetics with chronic kidney disease due to concerns about an increased risk of lactic acidosis.
Methodology of Analysis and Evaluated Patient Population
A study published last year analyzed data from patients with diabetes and chronic kidney disease from the TREAT study (The Trial to Reduce Cardiovascular Events with Aranesp Therapy) who were treated with metformin and compared them with patients who were not treated with metformin. The parameters monitored included overall mortality, cardiovascular mortality, the incidence of cardiovascular events (hospitalization for heart failure, myocardial infarction, stroke), end-stage renal disease (ESRD), and a composite renal outcome (ESRD or death).
In the TREAT study, 591 patients with diabetes and kidney disease used metformin, while 3,447 patients were not treated with metformin. Using the propensity score matching method, two mutually comparable groups of patients were created for comparison of the monitored parameters.
Results
In patients treated with metformin, overall mortality (hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.36−0.69), cardiovascular mortality (HR 0.49; 95% CI 0.32−0.74), the incidence of cardiovascular events (HR 0.67; 95% CI 0.51−0.88), and the composite renal outcome (HR 0.77; 95% CI 0.61−0.98) were lower than in patients who did not use metformin. The incidence of ESRD was marginally increased with metformin treatment (4.0 vs. 3.6%). Only 2 cases of lactic acidosis were reported.
Conclusion
The analysis of patients from the TREAT study suggested that the use of metformin in diabetics with stage 3 chronic kidney disease could lead to a reduction in overall mortality, cardiovascular mortality, and the frequency of cardiovascular events and could be safer than previously assumed.
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Reference: Charytan D. M., Solomon S. D., Ivanovich P. et al. Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 2019; 21: 1199−1208, doi: 10.1111/dom.13642.
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