The impact of sofosbuvir/velpatasvir/voxilaprevir treatment on serum hyperglycemia in hepatitis C virus infections: a systematic review and meta-analysis

Ann Med. 2023 Dec;55(1):463-479. doi: 10.1080/07853890.2023.2168745.

Abstract

Background: The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies.

Aim: To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection.

Methods: We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109).

Results: Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010-0.020; p < .001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727-198.160), the HCV genotype 3-genotype 1 IRR was 4.13 (95% confidence interval: 1.52-11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration.

Conclusion: Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary.

Keywords: Diabetes; Hepatitis C; Hyperglycemia; SOF/VEL/VOX.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / adverse effects
  • Drug Therapy, Combination
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C* / chemically induced
  • Hepatitis C* / complications
  • Hepatitis C* / drug therapy
  • Humans
  • Hyperglycemia* / epidemiology
  • Randomized Controlled Trials as Topic
  • Sofosbuvir / adverse effects
  • Sustained Virologic Response
  • Treatment Outcome

Substances

  • Sofosbuvir
  • voxilaprevir
  • velpatasvir
  • Antiviral Agents

Grants and funding

This work was supported by Ditmanson Medical Foundation Chia-Yi Christian Hospital [Grant No. R111-11]. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.