SGLT2 Inhibitors Superior to Other Oral Diabetes Drugs for People with Type 2 Diabetes and NAFLD

Sodium-glucose cotransporter 2 (SGLT2) inhibitors outperformed other oral diabetes drugs in combatting liver disease among people Type 2 diabetes and nonalcoholic fatty liver disease (NAFLD),according to results of a large study published in JAMA Internal Medicine today that used data from South Korea’s National Health Insurance Service.

Just over half of patients with Type 2 diabetes have NAFLD, and people with both conditions are more likely to develop nonalcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma and cardiovascular disease, according to corresponding author Won Kim, M.D., Ph.D., of the Seoul National University College of Medicine and colleagues.

The SGLT2 inhibitors include Jardiance (empagliflozin), Invokana (canagliflozin) and Farxiga (dapagliflozin). The study compared the SGLT2 inhibitors with the dipeptidyl peptidase-4 (DPP-4) inhibitors, which include Januvia (sitagliptin), Tradjenta (linagliptin) and Nesina (alogliptin); the thiazolidinediones, which include Actos (pioglitazone) and Avandia (rosiglitazone);and the sulfonylureas, which are available as generics and include glipizide, glimepiride and glyburide.

Kim and colleagues conducted the retrospective study by combing through the South Korean database to identify just over 80,000 people with type diabetes and NAFLD. All the patients included in study were also taking metformin, a commonly prescribed diabetes drug. They then categorized the patients by the type of diabetes drugs they were prescribed: 9,470 were prescribed a SGLT2 inhibitor; 55,324, a DPP-4 inhibitor; 2,191, a thiazolidinedione, and 13,193 sulfonylurea.

The primary endpoint was a surrogate marker for regression of NAFLD called the fatty liver index, which combines body-mass index, waist circumference, triglycerides and gamma-glutamyl transferase, a liver enzyme that can be measured in a blood sample that is indicator of liver damage. Kim and colleagues acknowledged that the fatty liver index “might be a weak proxy for NAFLD regression” but also said that many studies have shown that a decline in the fatty liver index over time indicates NAFLD regression.

The researchers looked examined trends in the patients’ fatty liver index over a 60-month period. Using a hazard ratio analysis, they found that the patients prescribed an SGLT2 inhibitor were nearly twice as likely to experience NAFLD regression (as measured by the fatty liver index) as the patients prescribed a sulfonylurea. Those prescribed a DPP-4 inhibitor were 45% more likely to experience NAFLD regression when compared with those prescribed a sulfonylurea and those prescribed a thiazolidinedione, 70% more likely.

The SGLT2 inhibitors also came out on top when it came to a secondary outcome of adverse liver-related items, a composite of liver-related hospitalizations, liver-related mortality, hepatocellular carcinoma and liver transplant.

Because this is an observational study, the results can’t be viewed as the last word on the subject, although the number of patients involved does make it strong observational study. Kim colleagues advised caution in interpreting their results.

On the other hand, they note that international clinical practice guidelines recommend screening people with Type 2 diabetes for NAFLD but they are silent on which diabetes drug to use in patients in which NAFLD is found.

“The results of this cohort demonstrated that SGLT2 inhibitors might have potential benefits for patients with both NAFLD and [Type 2 diabetes] compared with other [oral diabetes drug] classes,” they wrote in their conclusion.