Evidence mapPaperPMID 40808546Full record

Trial reportDiabetes, obesity & metabolism2025

Efficacy and safety of pioglitazone, empagliflozin and glimepiride as third-line agents in patients with type 2 diabetes inadequately controlled with metformin and DPP-4 inhibitors: A multicentre, phase 4 randomized controlled trial.

Yun Kyung Cho, Jae-Hyoung Cho, Sang-Mo Hong, Jung Hwan Park, Byung-Wan Lee, Jee Hee Yoo, Jae Hyeon Kim, Sung Wan Chun, You-Cheol Hwang, Kee-Ho Song and 1 more

Abstract readMulticenter StudyRandomized Controlled TrialClinical Trial, Phase IV
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yun Kyung ChoDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Jae-Hyoung ChoDepartment of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Sang-Mo HongDepartment of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea.
Jung Hwan ParkDepartment of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea.
Byung-Wan LeeDepartment of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0002-9899-4992
Jee Hee YooDepartment of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Republic of Korea.
Jae Hyeon KimDepartment of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Sung Wan ChunDepartment of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.ORCID https://orcid.org/0000-0001-7630-5204
You-Cheol HwangDepartment of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0003-4033-7874
Kee-Ho SongDepartment of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea.
Woo Je LeeDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0002-1899-3560

Funding

Yuhan
6 · The paper itself

Abstract

aimsTo assess the efficacy and safety of three triple-combination therapies in patients with type 2 diabetes (T2D) inadequately controlled on metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor. MATERIALS AND

methodsThis multicentre, prospective, randomised, open-label, parallel-group, phase 4 study included patients with T2D inadequately controlled on metformin (≥1000 mg) and a DPP-4 inhibitor. Participants were randomised to receive empagliflozin 10 mg/day (n = 61), pioglitazone 15 mg/day (n = 58) or glimepiride 2 mg/day (n = 57). The primary outcome was glycated haemoglobin (HbA1c) level change after 24 weeks of treatment.

resultsThe mean age, HbA1c level and diabetes duration of the patients were 58.5 ± 10.0 years, 7.8 ± 0.7% and 8.1 ± 5.6 years, respectively. HbA1c level decreased after treatment (-0.78 ± 0.09, empagliflozin; -0.89 ± 0.09, pioglitazone; and -0.93 ± 0.12 glimepiride). No significant differences were observed in HbA1c reduction among the three triple-combination therapies. The proportions of patients with HbA1c < 7.0% were similar across the three regimens (65.6%, empagliflozin; 56.9%, pioglitazone; and 63.2%, glimepiride). Significant weight loss was observed in the empagliflozin group (-1.73 ± 3.14 kg), whereas weight gain was observed in the pioglitazone and glimepiride groups (1.11 ± 3.97 kg and 1.11 ± 4.07 kg, respectively). The glimepiride group reported four hypoglycaemic episodes (6.56%), while none were reported in the other groups.

conclusionsThe addition of empagliflozin, pioglitazone, or glimepiride to metformin and DPP-4 inhibitors significantly improved glycaemic control in patients with T2D. The selection of a third agent should be individualized based on the patient characteristics.

Indexed as

Benzhydryl CompoundsDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsGlucosidesHypoglycemic AgentsSulfonylurea CompoundsThiazolidinedionesAgedBlood GlucoseDrug Therapy, CombinationFemaleGlycated HemoglobinHumansHypoglycemiaMaleMetforminBenzhydryl CompoundsBlood GlucoseDipeptidyl-Peptidase IV InhibitorsempagliflozinglimepirideGlucosidesGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsMetforminPioglitazoneSulfonylurea CompoundsThiazolidinedionesantidiabetic drugglycaemic controlphase IV studyrandomised trialtype 2 diabetes

Identifiers

PMID40808546
PMCPMC12515792

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.