Metformin use in the first year after kidney transplant, correlates, and associated outcomes in diabetic transplant recipients: A retrospective analysis of integrated registry and pharmacy claims data

Abstract

While guidelines support metformin as a therapeutic option for diabetic patients with mild-to-moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2015). Associations (adjusted hazard ratio, aHR ) of diabetes regimens (with and excluding metformin) in the first year post-transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post-transplant; most also received diabetes comedications. Compared to those who received insulin-based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.41 ), malignancy-related (aHR 0.45 ), and infection-related (aHR 0.32 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin-based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.

Impact of metformin on malignancy in solid organ transplantation

“…Vest et al 9 reported that the incidence of metformin use in a cohort of kidney transplant recipients within the first year post‐transplant was <5.0%. Within this study, median 1 year eGFR in both arms was >50 mL/min/1.73 m 2 , making metformin a viable option for the treatment of diabetes mellitus.…”

“…With the established risks of malignancy and diabetes after SOT, understanding metformin's role in this population is necessary. A registry analysis of kidney transplant recipients between 2007 and 2013 found that only 4.7% of patients had been prescribed metformin within the first year post‐transplant despite metformin use being associated with a reduction in all‐cause mortality, including malignancy‐related death, as well as all‐cause graft failure 9 . A recent publication reported that use of metformin in heart transplant recipients was associated with a 90% reduction in risk of malignancy in their diabetic population 10 .…”

Associations of obesity with antidiabetic medication use after living kidney donation: An analysis of linked national registry and pharmacy fill records

“…However, metformin has been linked to rare but fatal lactic acidosis complications, especially in patients with eGFR <30 mL/min per 1.73 m 2 , which has led the US Food and Drug Administration (FDA) to label it as contraindicated for such patients. Since most donors are expected to have eGFR levels >30 mL/min per 1.73 m 2 , use is likely safe and appropriate, but notably, concern for reduced kidney function was not a deterrent to use, in contrast with infrequent use in the transplant population at higher eGFR levels . In the context of obesity, even independent of diabetes, metformin may have benefit for weight loss.…”

“…At the crossroads of controversy in the implications of obesity in living donor selection, and in recognition of diabetes mellitus as an important cause of ESRD when it occurs in donors, pursuit of better understanding of the implications of pre‐donation obesity for comorbidity such as diabetes is warranted. Pharmacy claims offer a non‐obtrusive measure of prescribed health care that do not rely on patient self‐report and are increasingly used in observational investigations of large populations including transplant and donation‐related epidemiologic studies . To this end, we examined a novel linkage of national US transplant registry data with records from a pharmacy claims warehouse that identifies antidiabetic medication (ADM).…”

Administration of metformin in renal transplant patients with post-transplant diabetes mellitus

“…However, in later phases after transplantation, the NODAT agreement in 2003 did not endorse metformin as the first-line anti-diabetic drug because of safety concerns. In later phases after transplantation, sulfonylureas, meglitinides, dipeptidyl peptidase-4 inhibitors, alpha-glycosidase inhibitors, and rarely sodium-glucose co-transporter 2 (SGLT-2) inhibitors have been suggested as potential anti-glycemic agents (5,6). There is a need for further trial studies to verify an association between PTDM and metformin administration in high-risk renal transplant patients and to evaluate the risk-benefit balance using this drug (7).…”