Dataset Information

Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).

ABSTRACT:

Aim

Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale 'pragmatic' trials.

Methods

EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA(1c) > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA(1c) < 7% without hypoglycaemia or ? 3% increase in body weight.

Results

In this large group of T2DM patients, a second OAD was added at mean HbA(1c) of 8.2 ± 1.3%, with no baseline HbA(1c) difference between cohorts. Second-line OAD therapy attained the PEP in the majority of patients, with higher attainment in those prescribed a vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p < 0.001). In patients with baseline HbA(1c) ? 7%, SEP 3 was achieved by 35% of patients on a vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p < 0.001). Safety events were reported infrequently and safety profiles of vildagliptin and other OADs were consistent with previous data.

Conclusion

EDGE demonstrates that in a 'real-life' setting, vildagliptin as second OAD can lower HbA(1c) to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs.

SUBMITTER: Mathieu C

PROVIDER: S-EPMC4231206 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).

Mathieu C C Barnett A H AH Brath H H Conget I I de Castro J J JJ Göke R R Márquez Rodriguez E E Nilsson P M PM Pagkalos E E Penfornis A A Schaper N C NC Wangnoo S K SK Kothny W W Bader G G

International journal of clinical practice 20130821 10

<h4>Aim</h4>Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale 'pragmatic' trials.<h4>Methods</h4>EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physici ...[more]

PMID: 23961850

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Project description:ObjectivesMetformin is an established first-line treatment for type 2 diabetes mellitus (T2DM) patients but intensification of oral anti-diabetic therapy is usually required over time. The effectiveness of diabetes control with vildaGliptin and vildagliptin/mEtformin (EDGE) study compared effectiveness and safety of vildagliptin and other oral anti-diabetic drugs (OAD) in 45,868 patients worldwide with inadequately controlled T2DM by monotherapy under real-life conditions. Here, we present effectiveness results for patients receiving vildagliptin (vildagliptin cohort) or another OAD (comparator cohort) add-on to monotherapy in Bulgaria.MethodsThe eligible diabetes patients inadequately controlled with current monotherapy were assigned to add-on treatment, which was chosen by the physician based on patient's need. Effectiveness was assessed by glycated hemoglobin (HbA1c) drop and by means of a composite endpoint assessing the proportion of patients responding to treatment (HbA1c <7%) without proven hypoglycemic event and significant weight gain (>5%) after 12 months of treatment.ResultsIn total, 754 patients were enrolled in Bulgaria, 384 in the vildagliptin cohort and 369 in the comparator cohort. Mean HbA1c change from baseline was significantly higher with vildagliptin compared to the comparator (-1.35% in the vildagliptin cohort and -0.55% in the comparator cohort, P < 0.001). In the vildagliptin cohort, a higher proportion of patients reached the composite endpoint (HbA1c <7%, no hypoglycemic events, no weight gain) when compared to the comparator cohort (vildagliptin: 32.3%; comparator: 8.4%; P < 0.001). Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (3.4% versus 1.9% in the comparator group) and serious adverse events (2.3% versus 1.1% in the comparator group).ConclusionsIn real-life clinical practice in Bulgaria, vildagliptin is associated with a greater HbA1c drop, and a higher proportion of patients reaching target HbA1c without hypoglycemia and weight gain compared to comparator.

Project description:INTRODUCTION: A step-up strategy for dipeptidyl peptidase (DPP)-4 inhibitor-based regimens has not yet been established. In addition, similarities and differences between DPP-4 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists remain to be elucidated in humans. We investigated the pleiotropic effects of vildagliptin vs liraglutide in patients with type 2 diabetes on sitagliptin-based regimens in an open-label, randomized, clinical trial. MATERIALS AND METHODS: A total of 122 patients with type 2 diabetes that was inadequately controlled by sitagliptin-based regimens were randomly assigned to either vildagliptin (50 mg, twice daily) or liraglutide treatment (0.9 mg, once daily) for 12 weeks. The primary outcomes were glycated hemoglobin and body mass index. RESULTS: Both vildagliptin and liraglutide significantly lowered glycated hemoglobin within 12 weeks after switching from sitagliptin, but liraglutide produced a greater reduction (-0.67 ± 0.12% vs -0.36 ± 0.53%). Liraglutide lowered body mass index, whereas vildagliptin did not affect body mass index. Vildagliptin lowered fasting C-peptide immunoreactivity, but liraglutide did not. Vildagliptin increased serum levels of adiponectin, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, whereas liraglutide had no effect on these levels. Quality of life, assessed using the diabetes treatment satisfaction questionnaire, was not impaired in either group. The most common adverse events were gastrointestinal symptoms, which occurred with similar frequencies in both groups. CONCLUSIONS: Vildagliptin-mediated improvements in glycemic control did not correlate with indices for insulin secretion and insulin sensitivity. Switching from sitagliptin to liraglutide is useful in managing hyperglycemia and weight. Each agent exerts unique pleiotropic effects. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (no. 000004953).

Project description:IntroductionLittle data is available on patients with advanced non-squamous NSCLC treated with erlotinib specifically after failure of first-line pemetrexed-containing chemotherapy. We assessed the effectiveness, safety and tolerability of erlotinib in a real-world setting.MethodsProspective single-arm, open-label, multicenter, non-interventional study of erlotinib (150mg daily) in inoperable stage III/IV NSCLC after progression on first-line pemetrexed-containing chemotherapy without EGFR-mutation selection. Patients were followed according to routine practice and response assessment was performed using RECIST 1.1. The primary end point was progression-free survival (PFS). Secondary end points included best confirmed overall response rate (ORR), disease control rate (DCR), and overall survival (OS). Adverse events were recorded. An independent dataset was used to validate the results.ResultsIn all, 59 patients were screened, 57 enrolled, and 54 (36 men; median age 65 years) included in the per-protocol analysis. Median PFS was 1.8 (95% CI 1.4-2.6) months, with 11% (95% CI 5-21%) alive and progression-free at 6 months. The ORR was 0.0% (97.5% CI 0.0-6.8%) and the DCR 34.6% (95% CI 21.9-49.0%). Median overall survival was 5.8 (95% CI 3.3-8.6) months with 28% (95% CI 17-42%) alive at one year. Rash occurred in 60.7% (95% CI 46.7-73.5%), with severe rash in 12.5% (95% CI 5.1-24.1%). Any grade diarrhea was observed in 42.8% (95% CI 29.7-56.8%), with grade 3 occurring in 7.1% (95% CI 1.9-17.2%). Erlotinib was stopped in 21.0% (95% CI 11.3-33.9%) of patients due to adverse events, which were treatment related in 7%.ConclusionSecond-line erlotinib after pemetrexed treatment results in similar real-world outcomes as reported after non-pemetrexed containing first-line therapy. However, the overall duration of response in unselected patients remains limited and other effective treatments have in the meantime been introduced. No new safety signals were detected.

Project description:IntroductionMetformin is an established first-line treatment for patients with type 2 diabetes mellitus (T2DM), but treatment intensification with other oral antidiabetes drugs (OADs) is usually required over time. Effectiveness of diabetes control with vildagliptin and vildagliptin/metformin was a 1-year, large observational study of 45,868 patients with T2DM across 27 countries which assessed effectiveness and safety of vildagliptin as add-on therapy to other OADs versus other comparator OAD combinations. Here, we present the data from Germany.MethodsPatients inadequately controlled with monotherapy were eligible only after the add-on treatment was finalized. Patients were assigned to either vildagliptin or comparator OADs [sulfonylureas, thiazolidinediones, glinides, ?-glucosidase inhibitors or metformin, excluding dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon-like peptide-1 mimetic/analogues]. The primary efficacy endpoint was the proportion of patients achieving a glycosylated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event or weight gain ?5%. One secondary efficacy endpoint was the proportion of patients achieving HbA1c <7% without hypoglycemia and weight gain. Change in HbA1c from baseline to study endpoint and safety were assessed.ResultsOf 8,887 patients enrolled in Germany, 6,679 received vildagliptin and 1,695 received other OADs. The mean ± SD baseline age, HbA1c, and T2DM duration were 62.8 ± 11.0 years, 7.7 ± 1.2%, and 5.8 ± 4.9 years, respectively. The proportion of patients achieving the primary (34.5% vs. 30.5%, p < 0.01) and secondary (25.4% vs. 21.7%, p = 0.01) endpoints was higher with vildagliptin than comparator OADs. Vildagliptin showed a numerically greater reduction in HbA1c (0.7%) from baseline vs. comparator OADs (0.6%). The overall incidence of adverse events was similar.ConclusionIn real life, treatment with vildagliptin is associated with a higher proportion of patients reaching target HbA1c without hypoglycemia and weight gain compared with other OADs in Germany.

Project description:ObjectiveThe optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC) is unknown. Observational studies with a variety of designs have reported differing results. The objective of this study is to systematically summarize and interpret the published real-world evidence comparing sequential treatment for mRCC.MethodsA search was conducted in Medline and Embase (2009-2013), and conference proceedings from American Society of Clinical Oncology (ASCO), ASCO Genitourinary Cancers Symposium (ASCO-GU), and European Society for Medical Oncology (ESMO) (2011-2013). We systematically reviewed observational studies comparing second-line mRCC treatment with mammalian target of rapamycin inhibitors (mTORi) versus vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI). Studies were evaluated for 1) use of a retrospective cohort design after initiation of second-line therapy, 2) adjustment for patient characteristics, and 3) use of data from multiple centers. Meta-analyses were conducted for comparisons of overall survival (OS) and progression-free survival (PFS).ResultsTen studies reported OS and exhibited significant heterogeneity in estimated second-line treatment effects (I2 = 68%; P = 0.001). Four of these were adjusted, multicenter, retrospective cohort studies, and these showed no evidence of heterogeneity (I2 = 0%; P = 0.61) and a significant association between second-line mTORi (>75% everolimus) and longer OS compared to VEGF TKI (>60% sorafenib) (HR = 0.82, 95% CI: 0.68 to 0.98) in a meta-analysis. Seven studies comparing PFS showed significant heterogeneity overall and among the adjusted, multicenter, retrospective cohort studies. Real-world observational data for axitinib outcomes was limited at the time of this study.ConclusionsReal-world studies employed different designs and reported heterogeneous results comparing the effectiveness of second-line mTORi and VEGF TKI in the treatment of mRCC. Within the subset of adjusted, multicenter observational studies, second-line use of mTORi was associated with significantly prolonged survival compared with second-line use of VEGF TKI.

Dataset Information

Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).

Aim

Methods

Results

Conclusion

Publications

Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).

Similar Datasets

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