Treatment of insulin resistance with metformin in naïve genotype 1 chronic hepatitis C patients receiving peginterferon alfa-2a plus ribavirin

Authors


  • Presented at the 59th Annual Meeting of the American Association for the Study of the Liver Diseases, October 31 to November 4, 2008, San Francisco, CA.

  • Potential conflict of interest: M.R.-G.: consulting fees from Roche, Novartis, Bristol-Myers Squibb, AstraZenenca; lecture fees from Roche, Schering-Plough, Novartis, Bristol-Myers Squibb; unrestricted research grant support from Roche, Schering-Plough, Gilead; M.D.: consulting fees from Roche and Novartis; lecture fees from Roche, Schering-Plough, Novartis, Bristol-Myers Squibb; R.J.T.: consulting fees from Schering-Plough, Madaus, Novartis, Bristol-Myers Squibb; lecture fees from Roche, Schering-Plough, Novartis, Janssen, Bristol-Myers Squibb; grant support from Roche, Schering-Plough, SAE Consortium; J.L.C.: consulting fees from Roche, Novartis, Bristol-Myers Squibb; grant support from Roche, Schering-Plough, Gilead; J.S.: consulting fees from Novartis, Bristol-Myers Squibb, Schering-Plough; grant support from Roche; C.M.F.-R.: consulting fees from Schering-Plough, Roche-Farma, Bristol-Myers Squibb; lecture fees from Schering-Plough, Roche-Farma, Bristol-Myers Squibb; grant support from Roche-Farma and Schering-Plough; R.S.: consulting fees from Roche, Novartis, Bristol-Myers Squibb, Sigma-Tau, Gilead; lecture fees from Roche, Schering-Plough, Gilead, Novartis, Bristol-Myers Squibb; grant support from Roche, Gilead; J.G.-S.: consulting fees from Roche, Bristol-Myers Squibb, Novartis; lecture fees from Roche, Gilead Sciences; grant support from Roche and Gilead Sciences; J.M.H.: consulting fees from AstraZeneca and lectures from Roche Farma; M.D.l.M.: consulting fees from Schering-Plough; grant support from Roche; R.M.-O.: consulting and grants from Roche-Farma and Schering-Plough; S.D.: Consulting fees from Novo-Nordisk, Lilly, Boheringher Ingelheim, AstraZeneca; lecture fees from MSD, Servier, Roche-Farma, Novo-Nordisk and Lilly; R.P.: consulting fees from Roche-Farma, Novartis, Bristol-Myers Squibb; lecture fees from Gilead, Roche-Farma, Novartis, and Bristol-Myers Squibb; grant support from Gilead and Roche-Farma.

Abstract

Insulin resistance affects sustained virological response (SVR) in chronic hepatitis C. To know whether adding metformin to standard antiviral treatment improves SVR, we conducted a prospective, multicentered, randomized, double-blinded, placebo-controlled trial in 19 Spanish hospitals, including 123 consecutive patients with genotype 1 chronic hepatitis C and insulin resistance. Patients were randomized to receive either metformin (arm A; n = 59) or placebo (arm B; n = 64) in addition to peginterferon alfa-2a (180 μg/week) and ribavirin (1000–1200 mg/day). The primary end point was SVR, and secondary endpoints were viral clearance at weeks 12, 24, and 48, and changes in the homeostasis model assessment (HOMA) index over the first 24 weeks. There were no differences between arms at baseline. In the intent-to-treat analysis, SVR was observed in 53% versus 42% in arm A and arm B, respectively (P = NS). In the subgroup analyses, SVR was higher in females (n = 54) receiving metformin: arm A, 58% (15/26) versus 29% (8/28) arm B (P = 0.03). In the per protocol analysis (PPA; n = 101), SVR was 67% in arm A and 49% in arm B (P = 0.06). Viral decline during the first 12 weeks was greater in females receiving metformin: −4.88 (1.18) versus −4.0 (1.44) (P = 0.021), whereas no differences were seen in males. The triple therapy was well tolerated, but diarrhea was more often seen in arm A (34% versus 11%; P < 0.05). Conclusion: Adding metformin to peginterferon and ribavirin was safe and improved insulin sensitivity. Although the study failed to show a statistically significant difference between arms, it did show an improved SVR in females. (HEPATOLOGY 2009.)

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