Diabetes Metab J.  2022 Sep;46(5):689-700. 10.4093/dmj.2021.0183.

Comparison of Efficacy of Glimepiride, Alogliptin, and Alogliptin-Pioglitazone as the Initial Periods of Therapy in Patients with Poorly Controlled Type 2 Diabetes Mellitus: An Open-Label, Multicenter, Randomized, Controlled Study

  • 1Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
  • 2Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
  • 3Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 4Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
  • 5Department of Internal Medicine, Inje University Ilsan Paik Hospital, College of Medicine, Inje University, Goyang, Korea
  • 6Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
  • 7Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
  • 8Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 9Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea


The choice of an optimal oral hypoglycemic agent in the initial treatment periods for type 2 diabetes mellitus (T2DM) patients remains difficult and deliberate. We compared the efficacy and safety of glimepiride (GLIM), alogliptin (ALO), and alogliptin-pioglitazone (ALO-PIO) in poorly controlled T2DM patients with drug-naïve or metformin failure.
In this three-arm, multicenter, open-label, randomized, controlled trial, poorly controlled T2DM patients were randomized to receive GLIM (n=35), ALO (n=31), or ALO-PIO (n=33) therapy for 24 weeks. The primary endpoint was change in the mean glycosylated hemoglobin (HbA1c) levels at week 24 from baseline. Secondary endpoints were changes in HbA1c level at week 12 from baseline, fasting plasma glucose (FPG) levels, lipid profiles at weeks 12 and 24, and parameters of glycemic variability, assessed by continuous glucose monitoring for 24 weeks.
At weeks 12 and 24, the ALO-PIO group showed significant reduction in HbA1c levels compared to the ALO group (–0.96%±0.17% vs. –0.37%±0.17% at week 12; –1.13%±0.19% vs. –0.18%±0.2% at week 24). The ALO-PIO therapy caused greater reduction in FPG levels and significant increase in high-density lipoprotein cholesterol levels at weeks 12 and 24 than the ALO therapy. Compared to low-dose GLIM therapy, ALO-PIO therapy showed greater improvement in glycemic variability. The adverse events were similar among the three arms.
ALO-PIO combination therapy during the early period exerts better glycemic control than ALO monotherapy and excellency in glycemic variability than low-dose sulfonylurea therapy in uncontrolled, drug-naïve or metformin failed T2DM patients.


Alogliptin; Diabetes mellitus, type 2; Glimepiride; Glycemic control; Pioglitazone


  • Fig. 1. Study flowchart.

  • Fig. 2. Adjusted mean changes in (A) glycosylated hemoglobin (HbA1c) and (B) fasting plasma glucose from baseline at 12 weeks and 24 weeks during glimepiride (GLIM), alogliptin (ALO), or aloglipitin-pioglitazone (ALO-PIO) combination therapy. Error bar means and standard error of adjusted means. aP value <0.05 in analysis of covariance (ANCOVA).


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