MON-301 METFORMIN IN DIABETIC CKD STAGE 3-5: EXPANDING THE ROLE

Abstract

Metformin is recommended as first line drug in type-2 diabetics. Its use in diabetic nephropathy (DN) has been constrained by the perceived risk of lactic acidosis. Till recently it was restricted to subjects with serum creatinine < 1.5 mg/dL in males and < 1.4 mg/dL in females. In view of potential benefits, recent guidelines allow its use for eGFR <60 mL/min, but it remains contraindicated at eGFR <30. For eGFR in 30-45 range, it is recommended not to start metformin if pateint is not already on it. An observational cohort study was conducted to assess the short to medium term safety of metformin in DN (CKD Stage 3-5). Hypothesis: Metformin does not cause worsening of acidosis or increase in serum lactate levels in diabetic CKD. Inclusion criteria: DN patients (Stage 3-5 CKD) and who were on metformin at presentation to the nephrology clinic and wanted to continue metformin after discussing the options. The biochemical assessment was done at baseline and after a follow up of six months. The variables studied were venous bicarbonate; venous pH and lactate. The patients were specifically explained to be vigilant about any worsening and inform about any hospitalization or major illness. The study had 103 subjects. Mean age 61.6 years, 66% males, mean eGFR (CKD EPI) 21.2 ml/min and mean metformin dose 1081 mg/day. The proportion of subjects who were in Stages 3, 4 and 5 of CKD were 27, 25 and 48% respectively. Table 1Results of serum lactate, venous pH and serum bicarbonate at baseline and follow up*.n=103BaselineFollow upp-value #pH7.309 (0.038)7.303 (0.040)0.042Bicarbonate (mEq/L)18.89 (2.64)19.73 (1.90)0.001Lactate (mg/dL)**11.16 (3.86)10.92 (2.76)0.568*All values mean (SD); # Wilcoxon Signed Ranks Test** Normal lactate < 20 mg/dL Open table in a new tab Table 2Results segregated by CKD StageCKD StageeGFRBaseline pHFollow up pHBaseline BicarbonateFollow up BicarbonateBaseline LactateFollow up LactateCKD 343.09 (9.57)7.323 (0.03)7.307 (0.29)19.96 (2.02)20.53 (1.23)9.98 (2.89)10.40 (2.59)CKD 420.94 (4.69)7.311 (0.04)7.309 (0.03)19.34 (2.65)20.11 (1.84)11.80 (3.46)10.81 (2.42)CKD 58.79 (3.25)7.299 (0.03)7.298 (0.04)18.04 (2.05)19.08 (2.05)11.49 (4.43)11.28 (3.01) Open table in a new tab *All values mean (SD); # Wilcoxon Signed Ranks Test ** Normal lactate < 20 mg/dL All values as mean (SD). No patient developed overt episode of acidosis or increase in lactate level beyond normal levels. Two patients were on maintenance hemodialysis and did not show any worsening in the outcome variables. There was a significant increase in serum bicarbonate over time although of dubious clinical value. Metformin drug levels could not be performed due to non-availability of the assay. There were no major illnesses during this period in the study cohort attributable to worsening acidosis/lactic acidosis or mortality. This short-medium term follow up study did not detect any worsening of lactate, pH or plasma bicarbonate levels in patients with advanced CKD who continued their existent metformin dose. The current trend of allowing metformin in CKD might be extended to advanced CKD. There is a need for larger studies with longer follow up with drug level monitoring to establish the the safety of metformin in advanced CKD to deliver the benefits of this low cost and effective drug