Diabetes Metab J.  2020 Jul;44(S1):e46. 10.4093/dmj.2020.0107.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

  • 1Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
  • 2Department of Internal Medicine, Dong-A University Medical Center, Dong-A University College of Medicine, Busan, Korea
  • 3Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
  • 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
  • 5Department of Preventive Medicine, Jeonbuk National University Medical School, Jeonju, Korea
  • 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
  • 7Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
  • 8Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
  • 9Department of Internal Medicine, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
  • 10Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
  • 11Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
  • 12Department of Internal Medicine, Busan St. Mary’s Hospital, Busan, Korea


Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).
From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.
In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.
This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.


Diabetes mellitus, type 2; Drug therapy; combination; Hypoglycemic agents; Injections; Insulin
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