Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease

Abstract

Aims Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis. Materials and methods All‐cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non‐users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin‐alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non‐users and in multivariable proportional hazards models. Results There were 591 individuals who used metformin at baseline and 3447 non‐users. Among propensity‐matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non‐users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all‐cause mortality (HR, 0.49; 95% CI, 0.36‐0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32‐0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51‐0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61‐0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65‐1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed. Conclusions Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.

Metformin: time to review its role and safety in chronic kidney disease

“…Compared with sulfonylureas and other hypoglycaemic agents, metformin has been associated with a statistically significant lower risk of all‐cause mortality in people with type 2 diabetes and various stages of CKD, in both a Swedish population‐based longitudinal study ( n = 51 675) and a large cohort study of veterans ( n = 175 296). These results are in line with a newly published retrospective observational study that analysed data on survival, cardiovascular and kidney disease outcomes in metformin users ( n = 591) and non‐users ( n = 3447) with type 2 diabetes, CKD and anaemia (haemoglobin < 130 g/L) enrolled in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) . Propensity‐matched analysis demonstrated an independent association between metformin use and lower risk of all‐cause mortality (HR, 0.49; 95% CI, 0.36–0.69; P < 0.001), cardiovascular death (HR, 0.49; 95% CI, 0.32–0.74; P < 0.001) and cardiovascular events (HR, 0.66; 95% CI, 0.51–0.86; P = 0.002), a composite of non‐fatal myocardial infarction, congestive heart failure and stroke.…”

“…These results are in line with a newly published retrospective observational study that analysed data on survival, cardiovascular and kidney disease outcomes in metformin users (n = 591) and non-users (n = 3447) with type 2 diabetes, CKD and anaemia (haemoglobin < 130 g/L) enrolled in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT). 33 Propensity-matched analysis demonstrated an independent association between metformin use and lower risk of all-cause mortality (HR, 0.49; 95% CI, 0.36-0.69; P < 0.001), cardiovascular death (HR, 0.49; 95% CI, 0.32-0.74; P < 0.001) and cardiovascular events (HR, 0.66; 95% CI, 0.51-0.86; P = 0.002), a composite of non-fatal myocardial infarction, congestive heart failure and stroke. Of note, baseline characteristics in metformin users before propensity score matching were statistically different to non-users.…”

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

“…Studies have found that metformin not only has a hypoglycemic effect, but also has a protective effect on various diseases such as kidney cancer [5][6][7], pancreatic cancer, periodontal disease. Recent studies have also found that metformin has a positive effect on cardiovascular protection [8][9][10][11][12]. Metformin also lowers risk factors for cardiovascular disease such as blood fats [13][14][15], body weight and blood pressure.…”

Peter Theodore Ivanovich (1928‐2019)

“…Main topics were the investigation of diabetic patients [8][9][10] and optimized dosage of erythropoietin. 2,[11][12][13] Last but not least, it is important to note that Peter has held numerous positions in national and international societies reflecting again his conviction to promote mutual international understanding and involvement of the global dialysis industry. The International Society for Artificial Organs (ISAO) elected him Secretary General of the 5th World Congress in 1985 and Secretary Treasurer in 1990.…”

“…In order to promote high quality treatment options together with patient satisfaction, Peter’s interest and curiosity further stimulated him to be involved in clinical trials even after his formal retirement from his position as professor in medicine at Northwestern University in Chicago. Main topics were the investigation of diabetic patients and optimized dosage of erythropoietin …”