Dataset Information

Effectiveness and Tolerability of Second-Line Therapy with Vildagliptin Versus Other Oral Agents in Type 2 Diabetes (EDGE): Post Hoc Sub-Analysis of Bulgarian Data.

ABSTRACT:

Objectives

Metformin 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.

Methods

The 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.

Results

In 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).

Conclusions

In 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.

SUBMITTER: Kamenov Z

PROVIDER: S-EPMC4269645 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

Effectiveness and Tolerability of Second-Line Therapy with Vildagliptin Versus Other Oral Agents in Type 2 Diabetes (EDGE): Post Hoc Sub-Analysis of Bulgarian Data.

Kamenov Zdravko Z

Diabetes therapy : research, treatment and education of diabetes and related disorders 20140923 2

<h4>Objectives</h4>Metformin 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 pres ...[more]

PMID: 25245616

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Project description:AimReal-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.MethodsEDGE 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.ResultsIn 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.ConclusionEDGE 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.

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, α-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:Background and objectivesDiabetes is the leading cause of ESRD. Glucose control improves kidney outcomes. Most patients eventually require treatment intensification with second-line medications; however, the differential effects of those therapies on kidney function are unknown.Design, setting, participants & measurementsWe studied a retrospective cohort of veterans on metformin monotherapy from 2001 to 2008 who added either insulin or sulfonylurea and were followed through September of 2011. We used propensity score matching 1:4 for those who intensified with insulin versus sulfonylurea, respectively. The primary composite outcome was persistent decline in eGFR?35% from baseline (GFR event) or a diagnosis of ESRD. The secondary outcome was a GFR event, ESRD, or death. Outcome risks were compared using marginal structural models to account for time-varying covariates. The primary analysis required persistence with the intensified regimen. An effect modification of baseline eGFR and the intervention on both outcomes was evaluated.ResultsThere were 1989 patients on metformin and insulin and 7956 patients on metformin and sulfonylurea. Median patient age was 60 years old (interquartile range, 54-67), median hemoglobin A1c was 8.1% (interquartile range, 7.1%-9.9%), and median creatinine was 1.0 mg/dl (interquartile range, 0.9-1.1). The rate of GFR event or ESRD (primary outcome) was 31 versus 26 per 1000 person-years for those who added insulin versus sulfonylureas, respectively (adjusted hazard ratio, 1.27; 95% confidence interval, 0.99 to 1.63). The rate of GFR event, ESRD, or death was 64 versus 49 per 1000 person-years, respectively (adjusted hazard ratio, 1.33; 95% confidence interval, 1.11 to 1.59). Tests for a therapy by baseline eGFR interaction for both the primary and secondary outcomes were not significant (P=0.39 and P=0.12, respectively).ConclusionsAmong patients who intensified metformin monotherapy, the addition of insulin compared with a sulfonylurea was not associated with a higher rate of kidney outcomes but was associated with a higher rate of the composite outcome that included death. These risks were not modified by baseline eGFR.

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:IntroductionThe efficacy and safety of vildagliptin alone or with metformin is well established by randomized trials, but it is unknown whether it can be extrapolated to the real-world setting in Chinese patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness and safety of vildagliptin add-on to metformin versus dual oral antidiabetes drug (OAD), non-vildagliptin combination therapies in real-world Chinese patients with T2DM.MethodsThe China Prospective Diabetes Study was a post-marketing, prospective, multicenter, observational, real-world study conducted in 52 centers. Patients inadequately controlled with OAD monotherapy and who initiated vildagliptin add-on to metformin (VM cohort) or two OADs other than vildagliptin (comparator cohort) were included for the present analysis. The composite primary endpoint was glycated hemoglobin (HbA1c) < 7% and without tolerability events (hypoglycemia, weight gain ≥ 3%, or discontinuation due to gastrointestinal events) at 12 months. Secondary endpoints included change in HbA1c from baseline, subgroup analysis, and tolerability. Propensity score matching analysis was performed to adjust for baseline covariates imbalance (body mass index (BMI) and HbA1c).ResultsA total of 604 patients received VM and 670 received comparator therapy. Patients who received VM were younger, more obese, and had a higher baseline HbA1c and a shorter duration of T2DM. After propensity score matching, there were 530 patients per cohort. After 12-month treatment, the success rates of the composite primary endpoint were 50.9% and 33.0% in the VM and comparator cohorts, respectively (P < 0.001; odds ratio = 2.10, 95% confidence interval (CI) 1.64-2.70). Furthermore, the success rates of the composite endpoint were higher with VM across geographic area, BMI, and baseline HbA1c subgroups. Fewer tolerability events occurred in the VM cohort versus the comparator cohort (8.3% vs. 16.2%, P < 0.001; relative risk = 0.51, 95% CI 0.36-0.72).ConclusionCompared with dual OAD non-vildagliptin combination therapies, vildagliptin add-on to metformin is effective and safe to achieve glycemic control in Chinese patients with T2DM.FundingNovartis.

Project description:ImportanceImmune checkpoint inhibitors have been approved for use as a second-line therapy for hepatocellular carcinoma (HCC) in patients who previously received sorafenib. Pembrolizumab has shown substantial antitumor activity and a favorable toxicity profile as a second-line treatment of HCC. However, considering the high cost of pembrolizumab, there is a need to assess its value by considering both the clinical efficacy and cost.ObjectiveTo evaluate the cost-effectiveness of pembrolizumab vs placebo as second-line therapy in patients with HCC from the US payer perspective.Design, setting, and participantsA Markov model was developed to compare the lifetime cost and efficacy of pembrolizumab as a second-line treatment of HCC with those of placebo using outcome data from the KEYNOTE-240 randomized placebo-controlled trial, which included 413 patients with advanced HCC previously treated with sorafenib and randomized patients to receive pembrolizumab plus best supportive care or placebo plus best supportive care in a 2:1 ratio.Main outcomes and measuresLife-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were estimated at a willingness-to-pay threshold of $150 000 per QALY. One-way and probabilistic sensitivity analyses were performed to account for the parameter of uncertainty. A cost-threshold analysis was also performed. The study was conducted from January 31 to July 29, 2020.ResultsThe base-case model found that treatment with pembrolizumab was associated with increased overall cost by $47 057 and improved effectiveness by 0.138 QALYs compared with placebo, leading to an ICER of $340 409 per QALY. The model was most sensitive to the hazard ratio of overall survival (range, 0.61-1.00), health utility of placebo (range, 0.59-0.93), price of pembrolizumab (range, $5531-$8297), and price of postprogression therapies (range, $5596-$7944 for pembrolizumab and $4770-$7156 for placebo). The ICER of pembrolizumab was larger than $150 000 per QALY in most of the sensitivity and subgroup analyses. The price of pembrolizumab needed to be reduced by 57.7% to $2925 per cycle to achieve cost-effectiveness.Conclusions and relevanceThe findings of this cost-effectiveness analysis suggest that, at its current price, pembrolizumab is not a cost-effective second-line therapy for HCC in the US, with a willingness-to-pay threshold of $150 000 per QALY.

Dataset Information

Effectiveness and Tolerability of Second-Line Therapy with Vildagliptin Versus Other Oral Agents in Type 2 Diabetes (EDGE): Post Hoc Sub-Analysis of Bulgarian Data.

Objectives

Methods

Results

Conclusions

Publications

Effectiveness and Tolerability of Second-Line Therapy with Vildagliptin Versus Other Oral Agents in Type 2 Diabetes (EDGE): Post Hoc Sub-Analysis of Bulgarian Data.

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