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Efficacy and safety of teneligliptin in combination with pioglitazone in Japanese patients with type 2 diabetes mellitus.

ABSTRACT: To confirm the efficacy and safety of teneligliptin in combination with pioglitazone in Japanese patients with type 2 diabetes mellitus inadequately controlled with pioglitazone monotherapy.In an initial 12-week, double-blind, placebo controlled, parallel-group study, patients (n = 204) were randomized to teneligliptin 20 mg or placebo once daily added to their stable pioglitazone therapy. This was followed by a 40-week, open-label period during which all patients received teneligliptin once daily. The primary end-point was the change in hemoglobin A1c (HbA1c) from baseline to week 12.Patients in the teneligliptin group showed significantly greater reductions in HbA1c compared with the placebo group at week 12 (P < 0.001). The changes in HbA1c from baseline to week 12 were -0.9 ± 0.0% (least-squares mean ± standard error) in the teneligliptin group and -0.2 ± 0.0% in the placebo group. The change in fasting plasma glucose from baseline to week 12 was greater in the teneligliptin group than in the placebo group (P < 0.001). The blood glucose lowering effects of teneligliptin were sustained throughout the 40-week open-label period. Adverse events and adverse drug reactions occurred slightly more frequently in the teneligliptin group than in the placebo group, although the incidence of hypoglycemia was low. Bodyweight was unchanged in the double-blind period, but was slightly increased in the open-label period.Add-on therapy with teneligliptin was effective and generally well tolerated throughout the study period in Japanese patients with type 2 diabetes mellitus inadequately controlled with pioglitazone monotherapy. This trial was registered with ClinicalTrials.gov (no. NCT01026194).

SUBMITTER: Kadowaki T

PROVIDER: S-EPMC4020253 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Efficacy and safety of teneligliptin in combination with pioglitazone in Japanese patients with type 2 diabetes mellitus.

Kadowaki Takashi T Kondo Kazuoki K

Journal of diabetes investigation 20130527 6

<h4>Aim</h4>To confirm the efficacy and safety of teneligliptin in combination with pioglitazone in Japanese patients with type 2 diabetes mellitus inadequately controlled with pioglitazone monotherapy.<h4>Materials and methods</h4>In an initial 12-week, double-blind, placebo controlled, parallel-group study, patients (n = 204) were randomized to teneligliptin 20 mg or placebo once daily added to their stable pioglitazone therapy. This was followed by a 40-week, open-label period during which al ...[more]

PMID: 24843712

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Project description:INTRODUCTION:Teneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of teneligliptin have been demonstrated in clinical studies; however, data supporting its use in patients with moderate or severe renal impairment are limited. This interim analysis of a post-marketing surveillance of teneligliptin, exploRing the long-term efficacy and safety included cardiovascUlar events in patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY), aims to verify the long-term safety and efficacy of teneligliptin in Japanese patients with T2DM and impaired renal function. METHODS:For this analysis, we used the data from case report forms of the RUBY surveillance between May 2013 and June 2017. The patients were classified into G1-G5 stages of chronic kidney disease according to estimated glomerular filtration rate (eGFR) at initiation of teneligliptin treatment. Safety and efficacy were evaluated in these subgroups. Patients on dialysis were also assessed. Safety was assessed from adverse drug reactions (ADRs). Glycemic control was evaluated up to 2 years after teneligliptin initiation. RESULTS:A total of 11,677 patients were enrolled in the surveillance and 11,425 patient case-report forms were collected for the interim analysis. The incidence of ADRs in each subgroup was 2.98-6.98% of patients, with no differences in the ADR profile (including hypoglycemia and renal function ADRs) between subgroups. At 1 and 2 years after starting teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline was - 0.68 to - 0.85% and - 0.71 to - 0.85% across the eGFR groups, respectively. Treatment with teneligliptin in patients on dialysis reduced or tended to reduce glycated albumin levels [- 2.29%, (p < 0.001) after 1 year; - 1.64%, (p = 0.064) after 2 years]. CONCLUSIONS:During long-term treatment, teneligliptin was generally well tolerated in patients with any stage of renal impairment from normal to end-stage renal disease, including those on dialysis, and improved glycemic control. TRIAL REGISTRATION NUMBER:Japic CTI-153047. FUNDING:Mitsubishi Tanabe Pharma Corporation and Daiichi Sankyo Co, Ltd.

Project description:Background: Teneligliptin is a 3rd-generation dipeptidyl peptidase-4 (DPP-4) inhibitor. There is a limited evidence regarding the effect of teneligliptin. Therefore, this study is to assess the efficacy and safety of teneligliptin in type 2 diabetes mellitus (T2DM) patients with inadequately glycemic controlled. Methods: A search of PubMed, Medline, Embase, and The Cochrane Library during 2000.01-2018.03 was performed for randomized controlled trials of teneligliptin compared to placebo in patients with T2DM with monotherapy or add-on treatment. Results: Ten trials with 2119 patients were analyzed. Teneligliptin produced absolute reductions in glycated hemoglobin A1c (HbA1c) levels (weighted mean difference (WMD) 0.82%, 95% confidence interval (CI) [-0.91 to -0.72], p < 0.00001) compared with placebo. However, after 36-42 weeks of follow-up (open-label), HbA1c level rise higher than duration (double-blind) in teneligliptin group. Teneligliptin led to greater decrease of fasting plasma glucose (FPG) level (vs. placebo, WMD -18.32%, 95% CI [-21.05 to -15.60], p < 0.00001). Teneligliptin also significantly decreased the 2 h post-prandial plasma glucose (2 h PPG) (WMD -46.94%, 95% CI [-51.58 to -42.30], p < 0.00001) and area under the glucose plasma concentration-time curve from 0 to 2 h (AUC0-2h) for PPG (WMD -71.50%, 95% CI [-78.09 to -64.91], p < 0.00001) compared with placebo. Patients treated with teneligliptin achieved increased homeostasis model assessment of β cell function (HOMA-β) with 9.31 (WMD, 95% CI [7.78-10.85], p < 0.00001). However, there was no significant difference between teneligliptin and placebo in overall adverse effects (0.96 risk ratio (RR), 95% CI [0.87, 1.06], p = 0.06). The risks of hypoglycemia were not significantly different between teneligliptin and placebo (1.16 RR, 95% CI [0.59, 2.26], p = 0.66). Conclusions: Teneligliptin improved blood glucose levels and β-cells function with low risk of hypoglycemia in patients with T2DM. Common adverse effects of teneligliptin including hypoglycemia were identified and reviewed. Risks of cardiovascular events are less certain, and more data for long-term effects are needed.

Project description:Combination therapy with canagliflozin and insulin was investigated in a prescribed substudy of the canagliflozin Cardiovascular Assessment Study (CANVAS); however, it was not evaluated in Japanese patients with type 2 diabetes mellitus (T2DM). Since the usage profile of insulin therapy and pathologic features of Japanese patients differ from those of Caucasian patients, we determined the clinical benefit of such a combination therapy in Japanese patients.Patients who had inadequate glycemic control despite insulin, diet and exercise therapies were randomized into placebo (n = 70) and canagliflozin 100 mg (n = 76) groups that were administered once daily in addition to their prior insulin therapy in this double-blind, placebo-controlled study. The primary endpoint was the change in glycated hemoglobin (HbA1c) levels from the baseline to week 16.There was a statistically significant decrease in HbA1c levels from the baseline in the canagliflozin group (-0.97 ± 0.08 %) compared with the placebo group (0.13 ± 0.08 %) at week 16 [last observation carried forward (LOCF)]. The decrease in HbA1c levels in the canagliflozin group was independent of the insulin regimen (premixed, long-acting and long-acting plus rapid- or short-acting). Compared with the placebo group, canagliflozin significantly decreased fasting plasma glucose levels (-34.1 ± 4.8 vs -1.4 ± 5.0 mg/dL) and body weights (-2.13 ± 0.25 vs 0.24 ± 0.26 %), and significantly increased HDL cholesterol (3.3 ± 1.0 vs -0.5 ± 1.0 mg/dL) and HOMA2- %B (10.15 ± 1.37 vs 0.88 ± 1.42 %). The overall incidence of adverse events was similar between the two groups. The incidence and incidence per subject-year exposure of hypoglycemia (hypoglycemic symptoms and/or decreased blood glucose) were slightly higher in the canagliflozin group (40.0 % and 7.97) than in the placebo group (29.6 % and 4.51). However, hypoglycemic events in both groups were mild in severity and dose-reduction of insulin by <10 % from the baseline following hypoglycemic events decreased the incidence per subject-year exposure in the canagliflozin group. The incidence of hypoglycemia between the groups did not differ according to the insulin regimen.Canagliflozin in combination with insulin was effective in improving glycemic control and reducing body weight and well tolerated by Japanese patients with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT02220920.

Project description:BackgroundDiabetes has long been recognised as a strong, independent risk factor for cardiovascular disease, a problem which accounts for approximately 70% of all mortality in people with diabetes. Prospective studies show that compared to their non-diabetic counterparts, the relative risk of cardiovascular mortality for men with diabetes is two to three and for women with diabetes is three to four. The two biggest trials in type 2 diabetes, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP) study did not reveal a reduction of cardiovascular endpoints through improved metabolic control. Theoretical benefits of the newer peroxisome proliferator activated receptor gamma (PPAR-gamma) activators like pioglitazone on endothelial function and cardiovascular risk factors might result in fewer macrovascular disease events in people with type 2 diabetes mellitus.ObjectivesTo assess the effects of pioglitazone in the treatment of type 2 diabetes.Search strategyStudies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library. The last search was conducted in August 2006.Selection criteriaStudies were included if they were randomised controlled trials in adult people with type 2 diabetes mellitus and had a trial duration of at least 24 weeks.Data collection and analysisTwo authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analysis could be performed for adverse events only.Main resultsTwenty-two trials which randomised approximately 6200 people to pioglitazone treatment were identified. Longest duration of therapy was 34.5 months. Published studies of at least 24 weeks pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes like mortality, morbidity, adverse effects, costs and health-related quality of life are positively influenced by this compound. Metabolic control measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint did not demonstrate clinically relevant differences to other oral antidiabetic drugs. Occurrence of oedema was significantly raised. The results of the single trial with relevant clinical endpoints (Prospective Pioglitazone Clinical Trial In Macrovascular Events--PROactive study) have to be regarded as hypothesis-generating and need confirmation.Authors' conclusionsUntil new evidence becomes available, the benefit-risk ratio of pioglitazone remains unclear. Different therapeutic indications for pioglitazone of the two big U.S. and European drug agencies should be clarified to reduce uncertainties amongst patients and physicians.

Dataset Information

Efficacy and safety of teneligliptin in combination with pioglitazone in Japanese patients with type 2 diabetes mellitus.

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Efficacy and safety of teneligliptin in combination with pioglitazone in Japanese patients with type 2 diabetes mellitus.

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