The effect of canagliflozin on fatty liver disease and insulin production in patients with type 2 diabetes

The aim of this study was to investigate the effect of canagliflozin (Invokana) on insulin secretion and action along with changes in liver fat deposits and weight loss in patients with type 2 diabetes (T2D). The main finding of the study was that canagliflozin improved insulin secretion and usage, increased weight loss and decreased fat accumulation in the liver in these patients.

Canagliflozin is an SGLT-2 inhibitor, used to treat type 2 diabetes (T2D). It works by preventing sugar from being taken back up into the body after it is filtered out of the blood in the kidney. Instead, the sugar is removed from the body in the urine. Canagliflozin also improves weight loss and heart health.

Non-alcoholic fatty liver disease (NAFLD) is a disease associated with T2D. Patients with NAFLD have fat deposits in the liver called intrahepatic triglycerides (IHTG). They also have insulin insensitivity. This means that their body cells cannot use insulin (the hormone that controls blood sugar) properly to control blood sugar. NAFLD is also associated with high cholesterol and heart disease. Experimental studies have shown that canagliflozin can have beneficial effects on the liver. It is unknown if canagliflozin can reduce fat deposition in people with T2D.

56 patients with T2D were included in this study. They were randomly assigned to receive either canagliflozin 300mg or a placebo once a day for 24 weeks. IHTG, weight changes, insulin secretion, and insulin action were measured.

Canagliflozin reduced HbA1c (average blood sugar control over the last 3 months) by 0.71% and body weight by 3.4% compared to the placebo. In patients with NAFLD, there was a 6.9% reduction of IHTG in patients taking canagliflozin compared to 3.8% in the placebo group. 38% of patients treated with canagliflozin had weight loss greater than 5% of their body weight with a greater than 30% reduction in IHTG. Only 7% of the placebo group had the same results. Insulin sensitivity improved significantly in liver cells with canagliflozin treatment but not in muscle or fat cells. Insulin secretion and clearance also improved with canagliflozin.

The authors concluded that canagliflozin improves insulin sensitivity in the liver and insulin secretion while decreasing IHTG and body weight in patients with T2D.

This study was funded by Janssen Research & Development, the developer of canagliflozin. The number of patients included was quite small. Larger studies are needed to confirm these results.