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

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 [DPP4]). 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 + DPP4, 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 + DPP4 (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 + DPP4 suggested that LMET + DPP4 might reduce post‐breakfast GV to a greater degree than HMET in type 2 diabetes patients receiving low‐dose metformin monotherapy.