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CompletedNCT03499704EPIDOTEUpdated Mar 18, 2026

A Study to Evaluate the Effect of add-on Pioglitazone or Dapagliflozin in Participants With Type 2 Diabetes Mellitus Inadequately Controlled by DPP-4 Inhibitor and Metformin Therapy

A Phase 4 interventional study of Pioglitazone + Alogliptin and Alogliptin in Diabetes Mellitus, Type 2, sponsored by Celltrion Pharm, Inc.. Completed at 15 sites in South Korea. Open to participants aged 19 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-03-18.

Sponsored by Celltrion Pharm, Inc. · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
133
Allocation
Randomized
Ages
19 Years to 75 Years
Sex
All
01

Study summary

The purpose of this study is to assess the pioglitazone plus alogliptin plus metformin is non-inferior to dapagliflozin plus alogliptin plus metformin on glycosylated haemoglobin (HbA1c) change from baseline at Week 26.

Read the detailed description

The drug being tested in this study is Alogliptin Benzoate and Pioglitazone Hydrochloride FDC. This study will assess the efficacy of pioglitazone or dapagliflozin in participants with type 2 diabetes mellitus.

The study will enroll approximately 156 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups.

  • Pioglitazone 15 mg + Alogliptin 25 mg + Metformin >=500 mg
  • Dapagliflozin 10 mg + Alogliptin 25 mg + Metformin >=500 mg

Based on investigators opinion at Week 12, if participant has HbA1c >=7.5%, dose of pioglitazone can be titrated up to 30 mg.

This multi-center trial will be conducted in Republic of Korea. The overall time to participate in this study is up to 36 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 14 days after their last dose of drug for a follow-up assessment.

02

Conditions studied

  • Diabetes Mellitus, Type 2

Keywords

  • Drug therapy
03

Who can participate

Ages eligible
19 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. The subject is a regular outpatient with an has a historical diagnosis of type 2 diabetes.
  2. The subject has metabolic syndrome as jointly defined by the International Diabetes Federation (IDF); National Heart, Lung, and Blood Institute (NHLBI) / American Heart Association (AHA); and International Association for the Study of Obesity (IASO). If any 3 of the following 5 risk factors are present, metabolic syndrome can be considered:

    • High waist circumference: male ≥ 90 cm, female ≥ 85 cm.
    • High TGs (drug treatment for high TGs is an alternate indicator): ≥ 150 mg/dL (1.7 mmol/L).
    • Low HDL-C (drug treatment for low HDL-C is an alternate indicator): \< 40 mg/dL(1.0 mmol/L) in males, \< 50 mg/dL (1.3 mmol/L) in females.
    • High blood pressure (antihypertensive drug treatment in a subject with a history of hypertension is an alternate indicator): Systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg.
    • High fasting glucose (drug treatment of high glucose is an alternate indicator): ≥ 100 mg/dL.
  3. The subject has been receiving a stable dose of DPP-4 inhibitor + metformin therapy with diet and exercise for ≥ 3 months prior to Randomization.
  4. The subject has a HbA1c value between 7.0 and 11% inclusively within 28 days of Randomization via central laboratory test or after run-in period for 4 weeks via central laboratory test.

Exclusion criteria

Exclusion Criteria:

  1. The subject has type 1 diabetes, diabetic ketoacidosis, diabetic coma or diabetic precoma.
  2. The subject has an active bladder cancer or a history of bladder cancer.
  3. The use of any medications ie, oral or systemically injected glucocorticoids (including intra-articular injection), weight-loss drugs, insulin or other anti-diabetic drugs except DPP-4 inhibitor and metformin, within 3 months prior to randomization. Strong Cytochrome P450 2C8 (CYP2C8) inhibitors (eg, gemfibrozil, montelukast, quercetin, phenelzine) and CYP2C8 inducers (eg, rifampin) that in the opinion of the Investigator or Sponsor require treatment contraindicated during the study. The diuretics, angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) -inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) are to be used per product label with close monitoring under Investigator's supervision.
  4. Has genetic problems such as galactose intolerance, Lapp lactose dehydrogenase deficiency or glucose-galactose uptake disorder, etc.
  5. Has a history of alcohol abuse within 2 years prior to randomization.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
133 participants (actual)

Study arms

  • Experimental
    Pioglitazone + Alogliptin + Metformin (PAM)

    Pioglitazone 15 milligram (mg) and alogliptin 25 mg in fixed dose combination (FDC) tablet (SYR-322-4833), orally once daily and metformin greater than or equal to (\>=) 500 mg, tablet, orally, twice a day for up to 26 weeks. At Week 12, if participants has HbA1c \>=7.5%, pioglitazone dose will be titrated up to 30 mg based on investigator's opinion and up-titrated dose will be maintained up to Week 26.

    Drug: Pioglitazone + Alogliptin · Drug: Metformin

  • Active comparator
    Dapagliflozin + Alogliptin + Metformin (DAM)

    Dapagliflozin 10 mg, tablet, orally, once daily with alogliptin 25 mg, tablet, orally, once daily, and metformin \>=500 mg, tablet, orally, twice a day, for up to Week 26.

    Drug: Alogliptin · Drug: Metformin · Drug: Dapagliflozin

Interventions

  • DrugPioglitazone + Alogliptin

    Pioglitazone and Alogliptin FDC tablets

    Also known as: SYR-322-4833

  • DrugAlogliptin

    Alogliptin tablets.

  • DrugMetformin

    Metformin tablets.

  • DrugDapagliflozin

    Dapagliflozin tablets.

05

What researchers measure

Primary outcomes

  1. Mean Change from Baseline in HbA1c at Week 26

    Time frame: Baseline and Week 26

Secondary outcomes

  1. Mean Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 26

    HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR equal to (=) fasting insulin (micro unit per milliliter \[mcU/mL\])\*fasting glucose (millimole per milliliter \[mmol/mL\])/22.5. A higher number indicates a greater insulin resistance.

    Time frame: Baseline and Week 26

  2. Mean Change from Baseline in Serum Lipids at Week 26

    The change from baseline in serum lipids (Total Cholesterol \[TC\], Low-density Lipoprotein Cholesterol \[LDL-C\], High-density Lipoprotein Cholesterol \[HDL-C\], Triglycerides \[TGs\]) will be analyzed using mixed model repeated measures (MMRM) model.

    Time frame: Baseline and Week 26

  3. Number of Participants who Achieved an HbA1c Goal Target of Less than (<) 6.5 Percent (%) at Week 26

    Time frame: Week 26

06

Study locations

15 sites
  • The Catholic University of Korea, Bucheon, St. Marys Hospital
    Bucheon-si, Gyeonggi-do 14647, South Korea
  • Seoul National University Bundang Hospital
    Seongnam-si, Gyeonggi-do 13620, South Korea
  • The Catholic University of Korea, ST. Vincents Hospital
    Suwon, Gyeonggi-do 16247, South Korea
  • Ajou University Hospital
    Suwon, Gyeonggi-do 16499, South Korea
  • Inje University Haeundae Paik Hospital
    Busan, 48108, South Korea
  • Pusan National University Hospital
    Busan, 49241, South Korea
  • YeungNam University Hospital
    Daegu, 42415, South Korea
  • Daejeon Eulji Medical Center, Eulji University
    Daejeon, 35233, South Korea
  • Chosun University Hospital
    Gwangju, 61453, South Korea
  • Korea University Anam Hospital
    Seoul, 02841, South Korea
  • Kangbuk Samsung Hospital
    Seoul, 03181, South Korea
  • Yonsei University Health System Severance Hospital
    Seoul, 03722, South Korea
  • Kyung Hee University Hospital at Gangdong
    Seoul, 05278, South Korea
  • Samsung Medical Center
    Seoul, 06351, South Korea
  • Ulsan University Hospital
    Ulsan, 44033, South Korea
07

References and documents

Individual participant data

Plan to share: Yes — Celltrionpharm makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), and an opportunity for the primary publication of the research and final report development has been allowed. To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03499704
Lead sponsor
Celltrion Pharm, Inc.
Responsible party
Sponsor
First posted
Apr 17, 2018
Start date
Feb 11, 2020
Primary completion
Jan 2, 2024
Completion
Jan 16, 2024
Last update
Mar 18, 2026

Study contacts

Medical Team
study director · Celltrionpharm Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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