The NHS National Institute for Health Research (NIHR) Health Technology Assessment programme has featured a systematic review evaluating the use of insulin sensitisers (metformin, rosiglitazone and pioglitazone) for the management of non-alcoholic fatty liver disease (NAFLD), a condition associated with insulin resistance.

The systematic review included data from 15 randomised controlled trials:

• Four papers explored efficacy of pioglitazone

• One paper explored rosiglitazone,

• Eight papers explored metformin;

• Two compared metformin and rosiglitazone, although one used both metformin and rosiglitazone.

The duration of most trials was between 6 and 12 months. The following results were reported:

• Pioglitazone improved all parameters of liver histology. Pioglitazone reduced alanine aminotransferase (ALT) levels.

• Metformin showed mixed results, with ultrasound changes in two studies showing some improvement in steatosis, whereas there were no changes in the other two.

• Metformin, however, showed no improvement in non-alcoholic steatohepatitis (NASH) stages.

• Metformin showed greater reduction in glycosylated haemoglobin (–0.23% to –1.2% vs. –0.2% to –0.7%) and fasting plasma glucose (+0.05 to –3.19 mmol/L vs. –0.17 to –1.11 mmol/L) compared with pioglitazone.

• Metformin led to weight reduction (–4.3 to –6.7 kg), whereas participants on pioglitazone gained weight (+2.5 to +4.7 kg).

• Alanine aminotransferase levels were reduced with both metformin and pioglitazone; however, the reduction in levels with pioglitazone was not different to that caused by vitamin E.

The authors highlight some of the limitations of the studies included, stating that trials included had small numbers of patients, and details on how some of the trials conducted were not clear. They conclude that “Further trials of insulin sensitisers may not be the highest priority. Rosiglitazone has now been taken off the market because its cardiovascular safety was less than that of pioglitazone. However, pioglitazone has other adverse effects: weight gain, oedema and fractures. Metformin is safer, but had little effect on liver histology. The newer agents, the glucagon-like peptide-1 analogues, such as liraglutide, may be more worthy of a trial.”