Aim: Recently, the FDA endorsed metformin (MET) use in type 2 diabetes (T2D) patients with stage 3 CKD (CKD3). However, MET safety in elderly T2D subjects with CKD3 is unknown.

Methods: We studied lactic acid (LA) levels in ambulatory elderly male U.S. Veterans with stable nondiabetic CKD3 (eGFR 30-59ml/min/1.73m2) (Group 1) and diabetic CKD3 not on MET (Group 2) and on MET (Group 3) for at least 6 months. Hyperlactatemia was defined as LA >2mmol/L. Patients with history of HIV, advanced CHF, alcohol abuse, and liver cirrhosis were excluded. Clinical and biochemical characteristics were analyzed using ANOVA, χ2 test and Fisher’s exact tests.

Results: Mean LA levels were similar at 1.3±0.3 and 1.3±0.4 mmol/L in Group 1 (N=24, age 74.9±6.4 years, BMI 29.5±4.0kg/m2) and Group 2 (N=28, age 74.4±6.2 years, BMI 32.5±5.8kg/m2), respectively; while, LA was significantly higher in Group 3 (N=40, age 71.7±5.0 years, BMI 33.9±7.5kg/m2) at 2.0±1.0mmol/L compared with Group 2 subjects (P<0.001). Only 1 patient in each Group 1 (4.2%) and Group 2 (3.6%) had hyperlactatemia, as compared with 17 pts in Group 3 (42.5%) (P<0.05). Mild lactic acidosis (LA 5.2mmol/L, bicarbonate 18meq/L, anion gap 16) resolving with MET discontinuation was diagnosed in one Group 3 subject. Average daily MET dose in Group 3 was 1325±581mg and glycemic control was equal in Groups 2 and 3 (HbA1c 7.5±1.3 vs. 7.6±1.3%). There was no difference in mean LA level or frequency of hyperlactatemia between Group 3 pts with CKD stage 3A (eGFR 45-59, MET 1394±619mg/day) and stage 3B (eGFR 30-44, MET 1000±0mg/day). No differences in age, BMI, weight, eGFR, and HbA1c were seen in Group 3 pts with and without hyperlactatemia except trend towards higher MET dose in the hyperlactatemia patients (1500±560 vs. 1196±574 mg/day, P=0.1).

Conclusions: MET increases risk of hyperlactatemia in elderly men with T2D and CKD3 without clear predisposing factors while not offering explicit therapeutic advantage. We recommend using lower MET doses in elderly diabetic men with stage 3 CKD.

Disclosure

A.R. Gosmanov: None. E. Gosmanova: Advisory Panel; Self; Amgen Inc.

© 2019 by the American Diabetes Association.
2019
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