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July 18, 2014PLoS ONEOpen Access

Combined Vildagliptin and Metformin Exert Better Cardioprotection than Monotherapy against Ischemia-Reperfusion Injury in Obese-Insulin Resistant Rats

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Key result

Combined vildagliptin and metformin reduces arrhythmias and mortality vs monotherapy in insulin-resistant obese rats.

  • P<0.05
  • n=120

Why the study?

Does combined vildagliptin and metformin improve cardioprotection against ischemia-reperfusion injury in obese-insulin resistant rats compared to monotherapy?

Population

Male Wistar rats fed either high-fat diet (obese-insulin resistant model) or normal diet

Comparison

Combined vildagliptin and metformin for 21 days… vs Vildagliptin monotherapy, metformin monotherapy…

Design

Preclinical, Rats in each diet group were divided into 4 subgroups

Follow-up

21 days of treatment followed by 30-min ischemia and…

Authors

NANattayaporn ApaijaiKCKroekkiat ChindaSPSiripong Palee

Discussion

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Member takes

Overview

May support combined metformin-vildagliptin testing in obese I/R models; leaves open translation to human insulin-resistant hearts.

Structured PICO

Does combined vildagliptin and metformin improve cardioprotection against ischemia-reperfusion injury in obese-insulin resistant rats compared to monotherapy?

P
Population
Male Wistar rats fed a high-fat diet for 12 weeks to induce obese-insulin resistance, followed by 21 days of pharmacological treatment prior to ischemia-reperfusion injury.
I
Intervention
Combined vildagliptin and metformin for 21 days prior to ischemia-reperfusion
C
Comparator
Vildagliptin monotherapy, metformin monotherapy, or saline
O
Outcome
Metabolic parameters, heart rate variability, LV function, infarct size, mitochondrial function, calcium transient, Bax and Bcl-2, and Connexin 43 (Cx43)surrogate

Main Result

p-value: p=<0.05

In an obese-insulin resistant rat model, combined vildagliptin and metformin provided superior cardioprotection against ischemia-reperfusion injury compared to monotherapy by reducing arrhythmias and mortality.

Cite This Study

Apaijai et al. (2014) studied Obese-insulin resistance with ischemia-reperfusion injury (n=120). Combined vildagliptin and metformin vs. Vehicle (saline), vildagliptin monotherapy, or metformin monotherapy was evaluated on Arrhythmia score and mortality rate during ischemia-reperfusion (p=<0.05). Combined vildagliptin and metformin provided better cardioprotection than either monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats by reducing arrhythmia score and mortality rate.

synapsesocial.com/papers/6aa218330c07007fbcb2b30bhttps://doi.org/10.1371/journal.pone.0102374
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Cardioprotective Effects of Metformin and Vildagliptin in Adult Rats with Insulin Resistance Induced by a High-Fat Diet2012 · 89 citations
  2. 2Nitric oxide depresses connexin 43 after myocardial infarction in mice2008 · 21 citations
  3. 3Electrical remodeling contributes to complex tachyarrhythmias in connexin43‐deficient mouse hearts2007 · 71 citations
  4. 4Metformin Improves Insulin Signaling in Obese Rats via Reduced IKK<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math>Action in a Fiber-Type Specific Manner2010 · 23 citations
  5. 5Altered connexin43 expression produces arrhythmia substrate in heart failure2004 · 277 citations