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

J Diabetes Investig. 2019 May;10(3):714-722. doi: 10.1111/jdi.12922. Epub 2018 Oct 9.

Abstract

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.

Keywords: Continuous glucose monitoring; Dipeptidyl peptidase-4 inhibitor; Metformin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Biomarkers / analysis*
  • Blood Glucose / analysis
  • Blood Glucose Self-Monitoring
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Glycemic Index
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Linagliptin / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Prognosis

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Linagliptin
  • Metformin