Dataset Information

A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study.

ABSTRACT:

Aims

To compare the efficacy and safety of adding low-dose lobeglitazone (0.25 mg/day) or standard-dose lobeglitazone (0.5 mg/day) to patients with type 2 diabetes mellitus (T2DM) with inadequate glucose control on metformin and dipeptidyl peptidase (DPP4) inhibitor therapy.

Materials and methods

In this phase 4, multicentre, double-blind, randomized controlled, non-inferiority trial, patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor combination therapy were randomized to receive either low-dose or standard-dose lobeglitazone. The primary endpoint was non-inferiority of low-dose lobeglitazone in terms of glycaemic control, expressed as the difference in mean glycated haemoglobin levels at week 24 relative to baseline values and compared with standard-dose lobeglitazone, using 0.5% non-inferiority margin.

Results

At week 24, the mean glycated haemoglobin levels were 6.87 ± 0.54% and 6.68 ± 0.46% in low-dose and standard-dose lobeglitazone groups, respectively (p = .031). The between-group difference was 0.18% (95% confidence interval 0.017-0.345), showing non-inferiority of the low-dose lobeglitazone. Mean body weight changes were significantly greater in the standard-dose group (1.36 ± 2.23 kg) than in the low-dose group (0.50 ± 1.85 kg) at week 24. The changes in HOMA-IR, lipid profile and liver enzyme levels showed no significant difference between the groups. Overall treatment-emergent adverse events (including weight gain, oedema and hypoglycaemia) occurred more frequently in the standard-dose group.

Conclusions

Adding low-dose lobeglitazone to metformin and DPP4 inhibitor combination resulted in a non-inferior glucose-lowering outcome and fewer adverse events compared with standard-dose lobeglitazone. Therefore, low-dose lobeglitazone might be one option for individualized strategy in patients with T2DM.

SUBMITTER: Ryang S

PROVIDER: S-EPMC9541308 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study.

Ryang Soree S Kim Sang Soo SS Bae Ji Cheol JC Han Ji Min JM Kwon Su Kyoung SK Kim Young Il YI Nam-Goong Il Seong IS Kim Eun Sook ES Kim Mi-Kyung MK Lee Chang Won CW Yoo Soyeon S Koh Gwanpyo G Kwon Min Jeong MJ Park Jeong Hyun JH Kim In Joo IJ

Diabetes, obesity & metabolism 20220609 9

<h4>Aims</h4>To compare the efficacy and safety of adding low-dose lobeglitazone (0.25 mg/day) or standard-dose lobeglitazone (0.5 mg/day) to patients with type 2 diabetes mellitus (T2DM) with inadequate glucose control on metformin and dipeptidyl peptidase (DPP4) inhibitor therapy.<h4>Materials and methods</h4>In this phase 4, multicentre, double-blind, randomized controlled, non-inferiority trial, patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor combination therapy ...[more]

PMID: 35581902

Similar Datasets

Project description:IntroductionMetformin has dose-dependent hypoglycemic effects on patients with type 2 diabetes (T2D). In Japan, metformin has been prescribed at lower doses than in Western countries. We analyzed the effect of increasing the metformin dose on glycemic control and compared it to a combination therapy with dipeptidyl peptidase-4 inhibitors (DPP-4i) and a replacement therapy with DPP-4i.MethodsThis is a cohort study using a Japanese claims database. Patients with T2D who had been initially treated with low-dose metformin (≥ 500 mg/day and < 1000 mg/day) and then given a prescription change by increasing metformin to a higher dose (≥ 1000 mg/day) (increased-dose), adding DPP-4i (drug-added), or switching to DPP-4i (drug-switched) were included in this study. The primary outcome was the change in HbA1c levels at 12 months from the baseline period.ResultsAmong 2,726,437 patients with T2D, 494 were included. Of these patients, 226, 240, and 28 patients were classified as increased-dose, drug-added, and drug-switched groups, respectively. The HbA1c levels at 12 months from the index significantly decreased compared to that during the baseline period. The change was the highest in the drug-added group (- 1.06%), followed by the increased-dose (- 0.91%) and the drug-switched groups (- 0.37%). Among the subset of patients who did not receive any antidiabetic drugs other than metformin or DPP-4i, the highest change in HbA1c levels was observed in the increased-dose group (- 0.84%), followed by the drug-added (- 0.67%) and the drug-switched (- 0.42%) groups. The order of decrease from baseline remained the same for all the study groups after the propensity score weighting adjustment.ConclusionThe effect on glycemic control when increasing the metformin dose was studied in patients who had been receiving low-dose metformin. Increasing metformin dosage shows effectiveness and could be one of the next treatment options in patients who were prescribed low-dose metformin as the first-line treatment.

Project description:Although the glucose lowering effect of dipeptidyl peptidase-4 (DPP4) inhibitors is well established, several potential serious acute safety concerns have been raised including acute kidney injury, respiratory tract infections, and acute pancreatitis. Using the UK-based Clinical Practice Research Datalink (CPRD), we identified initiators (365-day washout period) of DPP4 inhibitors and relevant comparators including initiators of sulfonylureas, metformin, thiazolidinediones, and insulin between January 2007 and January 2016 to quantify the association between DPP4 inhibitors and three acute health events - acute kidney injury, respiratory tract infections, and acute pancreatitis. The associations between drug and study outcomes were estimated using Cox proportional hazard models adjusted for deciles of high-dimensional propensity scores and number of additional glucose lowering agents. After controlling for potential confounders, the risk was not significantly increased or decreased for initiators of DPP4 inhibitors compared to sulfonylureas (hazard ratio (HR) [95% confidence interval (CI)] for acute kidney injury: 0.81 [0.56-1.18]; HR for respiratory tract infections: 0.93 [0.84-1.04]; HR for acute pancreatitis 1.03 [0.42-2.52], metformin (HR for respiratory tract infection 0.91 [0.65-1.27]), thiazolidinediones (HR for acute kidney injury: 1.12 [0.60-2.10]; HR for respiratory tract infections: 1.02 [0.86-1.21]; HR for acute pancreatitis: 1.21 [0.25-5.72]), or insulin (HR for acute kidney injury: 1.40 [0.77-2.55]; HR for respiratory tract infections: 0.74 [0.60-0.92]; HR for acute pancreatitis: 1.01 [0.24-4.19]). Initiators of DPP4 inhibitors were associated with an increased risk of acute kidney injury when compared to metformin initiators (HR [95% CI] for acute kidney injury: 1.85 [1.10-3.12], although this association was attenuated when DPP4 inhibitor monotherapy was compared to metformin monotherapy exposure as a time-dependent variable (HR 1.39 [0.91-2.11]). Initiation of a DPP4 inhibitor was not associated with an increased risk of acute kidney injury, respiratory tract infections, or acute pancreatitis compared to sulfonylureas or other glucose-lowering therapies.

Dataset Information

A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study.

Aims

Materials and methods

Results

Conclusions

Publications

A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets