Diabetes Metab J.  2020 Feb;44(1):67-77. 10.4093/dmj.2018.0274.

Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study

• Kim JM
• Kim SS
• Kim JH
• Kim MK
• Kim TN
• Lee SH
• Lee CW
• Park JY
• Kim ES
• Lee KJ
• Choi YS
• Kim DK
• Kim IJ

• KMID: 2470956
• DOI: http://doi.org/10.4093/dmj.2018.0274

Abstract

BACKGROUND
There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.
METHODS
This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement.
RESULTS
Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P<0.001; glimepiride: −1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001).
CONCLUSION
Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Keyword

Dipeptidyl-peptidase IV inhibitors; Drug therapy, combination; Sulfonylurea compounds; Thiazolidinediones; Treatment failure

MeSH Terms

Cholesterol, HDL
Diabetes Mellitus, Type 2
Dipeptidyl-Peptidase IV Inhibitors
Drug Therapy, Combination
Hemoglobin A, Glycosylated
Humans
Hypoglycemia
Insulin Resistance
Metformin*
Sulfonylurea Compounds
Thiazolidinediones
Treatment Failure
Cholesterol, HDL
Dipeptidyl-Peptidase IV Inhibitors
Metformin
Sulfonylurea Compounds
Thiazolidinediones

Figure

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  Fig. 1 Study flowchart.

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  Fig. 2 Changes in the measured variables at 12 weeks and 26 weeks. Mean±standard error values at baseline, 12 weeks, and 26 weeks were calculated for (A) glycosylated hemoglobin (HbA1c), (B) homeostatic model assessment of insulin resistance (HOMA-IR), (C) high density lipoprotein cholesterol (HDL-C), and (D) triglycerides during 26-week treatments using glimepiride (closed triangles) or pioglitazone (closed quadrangles) for patients with type 2 diabetes mellitus who were concurrently receiving combination therapy using alogliptin and metformin. aP<0.05.

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