Insulin Resistance Med Raised SVR to 60%!!!

Study Results:
PegIntron + Ribavirin........... RVR 6.1%......SVR 38.7%
PegIntron+ Ribavirin+ Actos....RVR 27%.......SVR 60.4%



Liver Int. 2009 Nov 16.

Pioglitazone (Actos) improves virological response to peginterferon alpha-2b/ribavirin combination therapy in hepatitis C genotype 4 patients with insulin resistance.

Khattab M, Emad M, Abdelaleem A, Eslam M, Atef R, Shaker Y, Hamdy L. Department of Internal Medicine, Minya University, Minya, Egypt.

Background & aim: Insulin resistance (IR) affects sustained virological response (SVR). The use of insulin-sensitizing agents has been proposed to improve therapy outcome. The safety and efficacy of pioglitazone on insulin sensitivity and SVR in treatment-naïve patients with chronic hepatitis C (CHC) genotype 4 with IR receiving standard antiviral therapy were evaluated in a randomized-controlled study. Methods: Ninety-seven previously untreated patients with CHC and IR [homeostasis model assessment (HOMA>2)] were randomly assigned into two arms; (arm A; n=48) were given pioglitazone 30 mg/day combined with peginterferon (Peg-IFN)-alpha-2b/ribavirin (RBV) for 48 weeks, and (arm B; n=49) were given standard of care (Peg-IFN-alpha-2b/RBV for 48 weeks); HOMA index and hepatitis C virus RNA (HCV RNA) levels were measured at baseline, during therapy and follow-up. Treatment was stopped in patients without an early virological response or those who were HCV RNA positive at 24 weeks. Results: Baseline data of both groups were comparable, with no significant statistical differences. The percentages of rapid virological response (RVR) and SVR were significantly higher in patients given triple therapy compared with standard of care (27.08 vs. 6.1%; P=0.006 and 60.4 vs. 38.7%; P=0.04 respectively); patients in arm A showed a greater decrease in the HOMA index than those in arm B (-1.8 +/- 0.3, -2.1 +/- 0.3 vs. -1.1 +/- 0.6, -1.3 +/- 0.7) at week 24 and at the end of follow-up (P=0.001 at both time points). The triple therapy was well tolerated. Conclusions: A combination of pioglitazone, Peg-IFN-alpha-2b and ribavirin increased RVR, SVR and decreased IR, compared with patients given Peg-IFN plus ribavirin without an increase in adverse events.

http://www.ncbi.nlm.nih.gov/pubmed/19919569?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=81
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Additional info from the full text study.....

30% females (in both arms).
All patients were naive, genotype 4.
3 patients in the Actos arm and 4 in the SOC arm terminated early...5 for cytopenias (anemia, low neutrophils or platelets) and 2 for thyroid problems.  The 60% SVR is for ITT.  When you look only at those who completed the study, the results are even better.

Completers:
Peg+Riba+Pioglitazone ....SVR 69%  
Peg+Riba only..................SVR 44%

Procrit and Neupogen were not allowed.  


So I'm thinking SVR can be increased even more by:
Using Procrit/Neupogen when needed.
Tailoring the insulin-sensitizing therapy according to the HCV genotype and the degree of IR.  Sensitize people before starting treatment (don't start Tx until HOMA is below 2).
Find out which agent works best....a TZD, such as pioglitazone activating (PPARs) with a preeminent peripheral
effect, or a biguanide such as Metformin, with a mechanism of action specifically directed to the hepatic AMP-activated protein kinase.  

I say why not use both?  It works on diabetics.  

Co

[susan400]

That's fine, IF you actually have insulin resistance.  I have no such issues.  My A1C has remained normal for the past year despite repeating the tests over and over again.  My fasting blood glucose is in the normal range.  My weight is normal.  My doctor does not feel that I have any insulin resistance issues whatsoever and has no reason to run a fasting glucose tolerance test, even though I questioned him if this test would be a worthwhile test.  So, that issue has been put to rest.  

Susan400