We compared the bioequivalence, pharmacokinetics, and safety of metformin extended-release (MXR) tablets manufactured by Merck Pharmaceuticals Manufacturing (Jiangsu) Co., Ltd (Nantong, China) and Merck KGaA (Darmstadt, Germany) after a single oral dose under fasted/fed conditions. In this open-label phase 1 study, 54 healthy volunteers (fasted, n = 38; fed, n = 16) were randomly assigned to receive one 500-mg MXR tablet that was manufactured by Merck Pharmaceuticals Manufacturing (Jiangsu) Co. or Merck KGaA. Respectively, the mean terminal half-life was 7.5 and 6.8 hours in the fasted group, and 6.7 and 9.1 hours in the fed group. Median times to maximum observed concentration were 3 and 4 hours (fasted group) and 6 hours (both products, fed group). No significant differences were observed in the metformin plasma concentration-time curve (AUC) from time 0 to the last sampling time and maximum observed concentration between products. Geometric least square mean ratios for maximum observed concentration, AUC from time 0 to the last sampling time, and AUC from time 0 to infinity were nearly 100%; the corresponding 90%CIs for bioequivalence were within 80% to 125%. Diarrhea (26.4%), abdominal pain (5.7%), and nausea (3.8%) were the most common adverse events (AEs); AEs were mild. The mean AUC from time 0 to infinity (test and reference) was substantially increased by approximate to 45% in the fed condition (equivalent to a 1.5-fold dose increase); this means food increased net systemic availability but had no impact on AE incidence. This was considered in the study design, which included MXR administration with evening meals. MXR tablets were bioequivalent under fasted/fed conditions and were safe and well tolerated.