Dipeptidyl Peptidase-4 Inhibitors and Protection Against Stroke: A Systematic Review and Meta-Analysis

Barkas, Fotios

doi:10.26226/morressier.571f103fd462b8028d88c593

Cited by 24 publications

(17 citation statements)

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“…In view of the current cost of US$1.11 for a vildagliptin tablet and US$0.03 for a metformin tablet in Brazil, only a dramatic reduction in the price of vildagliptin would make this treatment become cost-effective in Brazil as monotherapy. Despite recent publications on the benefits of dual treatment with gliptins and metformin, doubts still remain about the choice of vildagliptin over other gliptins as well as the overall safety of the gliptins [14][15][16][17][18]. The lack of safety data precludes the proper assessment of complications associated with this disease or other potential events associated with vildagliptin and their costs.…”

Section: Discussionmentioning

confidence: 99%

“…However, other authors are more cautious about the impact of dual therapy with gliptins reducing cardiovascular risk [14]. Recent reviews have further pointed out that gliptins have a neutral effect on cardiovascular outcomes and stroke [15][16][17][18]. A crucial area in the management of patients with T2DM is adherence to medicines, which is typically seen as suboptimal across countries [3,[19][20][21], although studies have suggested greater compliance with metformin and the gliptins versus other combinations [22].…”

Section: Introductionmentioning

confidence: 99%

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Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in Brazil; findings and implications

Oliveira

Júnior

Godman

et al. 2017

Expert Review of Pharmacoeconomics & Outcomes Research

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Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and CRD, six studies were selected for the economic models. This study utilised cost data in the Brazilian health system to provide the context. Expert commentary: Type 2 diabetes mellitus is an epidemic disease and represents a challenge for all health care systems. Although guidelines clearly define first-line treatment, there are several other promising treatments. Vildagliptin is one of them, resulting in a mean lifetime increase of 0.31 years compared to metformin alone and 1.19 more life years compared to other metformin combinations. Considering observational data, life years with dual vildagliptin-containing treatments were 0.37 more compared to other dual treatments. However, its high cost versus generic metformin and its unclear safety profile weakens its subsequent cost-effectiveness. Consequently, the incorporation of vildagliptin or its combination with metformin is currently not recommended for the Brazilian Health Care System. This may change as more data becomes available.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in Brazil; findings and implications

Oliveira

Júnior

Godman

et al. 2017

Expert Review of Pharmacoeconomics & Outcomes Research

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“…This analysis included the most recent cardiovascular outcome trials with saxagliptin, alogliptin and sitagliptin; compared with placebo, no difference was found in the risk of stroke with gliptin treatment [odds ratio (OR) 0.996, 95% CI 0.850-1.166, P = 0.958] [11]. The controversy between the pre-clinical experimental and human trials was attributed to the fact that, in contrast to GLP-1R agonists, gliptins do not cross the blood-brain barrier and they do not similarly increase the levels of plasma GLP-1 [11]. Given the positive effect of GLP-1R agonists on weight gain, blood pressure and serum lipids along with the beneficial results of the experimental studies, trials with these agents were awaited with the expectation of proving their neuroprotective effect against stroke in clinical practice [19].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, two trials involving stroke patients with T2DM and patients with insulin resistance showed that treatment with pioglitazone was associated with a reduction in the risk of recurrent stroke [8,9]. In the SUSTAIN-6 trial (Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes), semaglutide reduced the risk of stroke by as much as 39% in T2DM patients at high cardiovascular risk [10] positive protection against stroke mediated by DPP-4 inhibitor (gliptin) treatment was not confirmed by a previous meta-analysis [11].…”

Section: Introductionmentioning

confidence: 99%

“…Flow chart showing selection of studies for meta-analysis.© 2019 EAN STROKE AND GLP1-R AGONISTS encouraging data in favour of their protective role against stroke[11]. The SPEAD-A (Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis) and SPIKE (Sitagliptin Preventive Study of Intimamedia Thickness Evaluation) trials showed that a 2year treatment with sitagliptin or alogliptin reduced the progression of carotid atherosclerosis in cardiovascular-disease-free diabetic individuals compared with conventional treatment[18].…”

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confidence: 99%

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Protection against stroke with glucagon‐like peptide 1 receptor agonists: a systematic review and meta‐analysis

Barkas

Elisaf

Milionis

2019

Euro J of Neurology

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In experimental stroke models pretreatment with the newly introduced antidiabetic agents, glucagon‐like peptide 1 receptor (GLP‐1R) agonists, has been shown to exert neuroprotective effects. Published evidence with regard to the effect of treatment with GLP‐1R agonists on the risk of stroke was evaluated. Data from prospective randomized placebo‐controlled trials up to October 2018 involving GLP‐1R agonists which reported cardiovascular outcomes as primary end‐points of efficacy and/or safety were meta‐analysed. Five eligible multicentre randomized placebo‐controlled trials (ELIXA, LEADER, SUSTAIN, EXSCEL and HARMONY) were included. The pooled analysis (n = 42 358) showed a significant reduction by 13% in the risk of total stroke from treatment with GLP‐1R agonists versus placebo (risk ratio 0.87, 95% confidence interval 0.78–0.98, P = 0.021) with no significant heterogeneity between trials (Q = 4.094, P = 0.393, I2 = 2.307%). When only fatal stroke was included (this applied for the ELIXA, LEADER, EXSCEL and HARMONY trials), active treatment was associated with a non‐significant reduction by 16% compared with placebo (risk ratio 0.84, 95% confidence interval 0.60–1.17, P = 0.29). The findings of this meta‐analysis support the evidence from earlier experimental studies calling attention to potential ‘stroke protective’ effects from treatment with GLP‐1R.

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Role of diabetes in stroke: Recent advances in pathophysiology and clinical management

Bradley

Spring

Beran

et al. 2021

Diabetes Metabolism Res

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The increasing prevalence of diabetes and stroke is a major global public health concern. Specifically, acute stroke patients, with pre-existing diabetes, pose a clinical challenge. It is established that diabetes is associated with a worse prognosis after acute stroke and the various biological factors that mediate poor recovery profiles in diabetic patients is unknown. The level of association and impact of diabetes, in the setting of reperfusion therapy, is yet to be determined. This article presents a comprehensive overview of the current knowledge of the role of diabetes in stroke, therapeutic strategies for primary and secondary prevention of cardiovascular disease and/or stroke in diabetes, and various therapeutic considerations that may apply during pre-stroke, acute, sub-acute and post-stroke stages. The early diagnosis of diabetes as a comorbidity for stroke, as well as tailored post-stroke management of diabetes, is pivotal to our efforts to limit the burden. Increasing awareness and involvement of neurologists in the management of diabetes and other cardiovascular risk factors is desirable towards improving stroke prevention and efficacy of reperfusion therapy in acute stroke patients with diabetes.

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Dipeptidyl Peptidase-4 Inhibitors and Protection Against Stroke: A Systematic Review and Meta-Analysis

Cited by 24 publications

References 0 publications

Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in Brazil; findings and implications

Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in Brazil; findings and implications

Protection against stroke with glucagon‐like peptide 1 receptor agonists: a systematic review and meta‐analysis

Role of diabetes in stroke: Recent advances in pathophysiology and clinical management

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