also from Novartis, is an inhibitor of sodium-glucose co-transporters 1 and 2
(SGLT1/2) that blocks glucose absorption from the gut and reabsorption by the
presented findings from a phase IIa study of 77 people who either had
biopsy-confirmed NASH with stage F1-F3 fibrosis or who were overweight and had
type 2 diabetes and elevated ALT. More than half were women and the median age
was about 50 years. The average body mass index was about 35 and the mean liver
fat fraction was about 21%.
were randomly assigned to receive 30mg or 150mg licogliflozin or a placebo for
levels declined in both licogliflozin groups while remaining stable in the
placebo group. At the end of the study, ALT levels were 36% lower in the 30mg
group and 43% lower in the 150mg group, with the latter difference being
statistically significant. AST and GGT levels declined
significantly in both dose groups, as did blood glucose levels as indicated by
decreased by an average of -5.28% and -7.02% in the 30mg and 150mg groups,
compared with -2.57% in the placebo group. At the end of treatment, 63%, 44%
and 19%, respectively, experienced at least a 5% absolute liver fat reduction,
while 67%, 40% and 25%, respectively, had at least a 30% relative reduction; these
differences were significant for the higher-dose group.
biomarkers of liver fibrosis did not change significantly in either
licogliflozin dose group overall, but some significant decreases were seen when
limiting the analysis to those with more extensive fibrosis at baseline.
weight declined significantly in both
licogliflozin groups – a loss of -3.88% of baseline body weight in the low-dose
group and -4.54% in the high-dose group – while remaining stable in the placebo
group. Waist circumference decreased by an average of -2.44cm and -4.02cm in
the licogliflozin groups but increased by 1.47cm in the placebo group.
too, was generally safe and well tolerated. The most common side effect was
diarrhoea, which was about twice as common in the 150mg group compared with the
30mg and placebo groups (77%, 40% and 39%, respectively), but it was mostly
mild. One person in each group stopped treatment because of adverse events.