PMID- 38310875
OWN - NLM
STAT- Publisher
LR  - 20240204
IS  - 2233-6087 (Electronic)
IS  - 2233-6079 (Linking)
DP  - 2024 Feb 2
TI  - Pioglitazone as Add-on THERAPY in Patients with Type 2 Diabetes Mellitus 
      Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, 
      Randomized, Placebo-Controlled Trial.
LID - 10.4093/dmj.2023.0314 [doi]
AB  - BACKGROUND: This study assessed the efficacy and safety of triple therapy with 
      pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes 
      mellitus (T2DM) inadequately controlled with metformin and dapagliflozin. 
      METHODS: In this multicenter, double-blind, randomized, phase 3 study, patients 
      with T2DM with an inadequate response to treatment with metformin (>/=1,000 mg/day) 
      plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 
      15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the 
      change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 
      (ClinicalTrials.gov identifier: NCT05101135). RESULTS: At week 24, the adjusted 
      mean change from baseline in HbA1c level compared with placebo was significantly 
      greater with pioglitazone treatment (-0.47%; 95% confidence interval, -0.61 to 
      -0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at 
      week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin 
      and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; 
      P<0.0001 for all). The addition of pioglitazone also significantly improved 
      triglyceride, highdensity lipoprotein cholesterol levels, and homeostatic model 
      assessment of insulin resistance levels, while placebo did not. The incidence of 
      treatment-emergent adverse events was similar between the groups, and the 
      incidence of fluid retention-related side effects by pioglitazone was low (1.5%). 
      CONCLUSION: Triple therapy with the addition of 15 mg/day of pioglitazone to 
      dapagliflozin plus metformin was well tolerated and produced significant 
      improvements in HbA1c in patients with T2DM inadequately controlled with 
      dapagliflozin plus metformin.
FAU - Heo, Ji Hye
AU  - Heo JH
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym 
      University Sacred Heart Hospital, Anyang, Korea.
FAU - Han, Kyung Ah
AU  - Han KA
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Nowon 
      Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea.
FAU - Hong, Jun Hwa
AU  - Hong JH
AD  - Division of Endocrinology, Department of Internal Medicine, Daejeon Eulji Medical 
      Center, Eulji University School of Medicine, Daejeon, Korea.
FAU - Seo, Hyun-Ae
AU  - Seo HA
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Daegu 
      Fatima Hospital, Daegu, Korea.
FAU - Hong, Eun-Gyoung
AU  - Hong EG
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym 
      University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
FAU - Yu, Jae Myung
AU  - Yu JM
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym 
      University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, 
      Seoul, Korea.
FAU - Jung, Hye Seung
AU  - Jung HS
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Korea.
FAU - Cha, Bong-Soo
AU  - Cha BS
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei 
      University College of Medicine, Seoul, Korea.
LA  - eng
SI  - ClinicalTrials.gov/NCT05101135
PT  - Journal Article
DEP - 20240202
PL  - Korea (South)
TA  - Diabetes Metab J
JT  - Diabetes & metabolism journal
JID - 101556588
SB  - IM
OTO - NOTNLM
OT  - Cardiovascular diseases
OT  - Diabetes mellitus, type 2
OT  - Insulin resistance
OT  - Sodium-glucose transporter 2 inhibitors
OT  - Thiazolidinediones
EDAT- 2024/02/05 00:42
MHDA- 2024/02/05 00:42
CRDT- 2024/02/04 18:46
PHST- 2023/09/01 00:00 [received]
PHST- 2023/10/25 00:00 [accepted]
PHST- 2024/02/05 00:42 [medline]
PHST- 2024/02/05 00:42 [pubmed]
PHST- 2024/02/04 18:46 [entrez]
AID - dmj.2023.0314 [pii]
AID - 10.4093/dmj.2023.0314 [doi]
PST - aheadofprint
SO  - Diabetes Metab J. 2024 Feb 2. doi: 10.4093/dmj.2023.0314.