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Aims/Introduction  The present study investigated the effect of high‐dose metformin or low‐dose metformin/linagliptin combination therapy on glycemic variability ( GV ) in type 2 diabetes patients with insufficient glycemic control despite low‐dose metformin monotherapy in a cross‐over study using continuous glucose monitoring.    Materials and Methods  The present study was carried out with 11 type 2 diabetes outpatients (7% < glycated hemoglobin < 10%) receiving low‐dose metformin monotherapy (500–1,000 mg). All patients were assigned to either metformin 1,500 mg monotherapy ( HMET ) or combination therapy of low‐dose (750 mg) metformin and linagliptin 5 mg ( LMET  + dipeptidyl peptidase‐4 [ DPP 4]).  GV  was evaluated by continuous glucose monitoring after >4 weeks of the initial treatment and again after cross‐over to the other treatment.  GV  metrics were compared between the treatments using the Wilcoxon signed‐rank test.    Results  Of the continuous glucose monitoring‐derived  GV  metrics for the  HMET  versus  LMET  +  DPP 4, mean glucose levels, standard deviations and mean amplitude of glucose excursions were not significantly different. Although the pre‐breakfast glucose levels were not significantly different among the treatments ( P  = 0.248), the 3‐h postprandial glucose area under the curve (>160 mg/ dL ) after breakfast was significantly larger with  HMET  versus  LMET  +  DPP 4 (9,550 [2,075–11,395] vs 4,065 [1,950–8,895];  P  = 0.041).    Conclusions  A comparison of  GV  with  HMET  versus  LMET  +  DPP 4 suggested that  LMET  +  DPP 4 might reduce post‐breakfast  GV  to a greater degree than  HMET  in type 2 diabetes patients receiving low‐dose metformin monotherapy.

journal of diabetes investigation

Which is better, high‐dose metformin monotherapy or low‐dose metformin/linagliptin combination therapy, in improving glycemic variability in type 2 diabetes patients with insufficient glycemic control despite low‐dose metformin monotherapy? A randomized, cross‐over, continuous glucose monitoring‐based pilot study