TOPLINE:
Metformin cuts the risk for diabetic nephropathy (DN) and major kidney and cardiovascular events in patients with newly diagnosed type 2 diabetes (T2D) across various renal function states.
METHODOLOGY:
Metformin is a first-line treatment in US and South Korean T2D management guidelines, except for patients with advanced chronic kidney disease (CKD) (stage, ≥ 4; estimated glomerular filtration rate [eGFR], < 30).
The study used data from the databases of three tertiary hospitals in South Korea to assess the effect of metformin on long-term renal and cardiovascular outcomes across various renal function states in patients with newly diagnosed T2D.
Four groups of treatment-control comparative cohorts were identified at each hospital: Patients who had not yet developed DN at T2D diagnosis (mean age in treatment and control cohorts, 61-65 years) and those with reduced renal function (CKD stages 3A, 3B, and 4).
Patients who continuously received metformin after T2D diagnosis and beyond the observation period were 1:1 propensity score matched with controls who were prescribed oral hypoglycemic agents other than metformin.
Primary outcomes were net major adverse cardiovascular events including strokes (MACEs) or in-hospital death and a composite of major adverse kidney events (MAKEs) or in-hospital death.
TAKEAWAY:
Among patients without DN at T2D diagnosis, the continuous use of metformin vs other oral hypoglycemic agents was associated with a lower risk for:
Overt DN (incidence rate ratio [IRR], 0.82; 95% CI, 0.71-0.95),
MACEs (IRR, 0.76; 95% CI, 0.64-0.92), and
MAKEs (IRR, 0.45; 95% CI, 0.33-0.62).
Compared with non-metformin or discontinued metformin use, the continuous use of metformin was associated with a lower risk for MACE across CKD stages 3A (IRR, 0.70; 95% CI, 0.57-0.87), 3B (IRR, 0.83; 95% CI, 0.74-0.93), and 4 (IRR, 0.71; 95% CI, 0.60-0.85).
Similarly, the risk for MAKE was lower among continuous metformin users than in nonusers or discontinuous metformin users across CKD stage 3A (IRR, 0.39; 95% CI, 0.35-0.43), 3B (IRR, 0.44; 95% CI, 0.40-0.48), and 4 (IRR, 0.45; 95% CI, 0.39-0.51).
IN PRACTICE:
“The significance of the current study is highlighted by its integration of real-world clinical data, which encompasses patients diagnosed with CDK4 [eGRF, 15-29 mL/min/1.73 m2], a group currently considered contraindicated,” the authors wrote.
SOURCE:
The study, led by Yongjin Yi, MD, PhD, Department of Internal Medicine, Dankook University College of Medicine, Cheonan-si, Republic of Korea, was published in Scientific Reports .
LIMITATIONS:
There may be a possibility of selection bias because of the retrospective and observational nature of this study. Despite achieving a 1:1 propensity score matching to address the confounding factors, some variables, such as serum albumin and A1c levels, remained unbalanced after matching. The paper did not include observation length or patient numbers, but in response to an email query from Medscape, Yi notes that in one hospital, the mean duration of observation for the control and treatment groups was about 6.5 years, and the total number in the treatment groups across data from three hospitals was 11,675, with the same number of matched controls.
DISCLOSURES:
This study was supported by a Young Investigator Research Grant from the Korean Society of Nephrology, a grant from the Seoul National University Bundang Hospital Research Fund, and the Bio&Medical Technology Development Program of the National Research Foundation funded by the Korean government. The authors disclosed no competing interests.
A version of this article appeared on Medscape.com.