Spotlight on liver health in diabetes

Several recent studies looked at prevention, recognition, and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with type 2 diabetes.

A systematic review, published by Diabetic Medicine on Sept. 28, analyzed the effects of glucose-lowering drugs on liver-related outcomes in type 2 diabetes. It included 10 cohort studies with 1,274,641 participants, all of whom had diabetes and no liver disease other than MASLD at baseline. Studied drugs included sulfonylureas, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, thiazolidinediones, insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors. It found that SGLT-2 inhibitors were associated with the strongest reduction in MASLD incidence, cirrhosis, and a composite of liver-related events, but only GLP-1 receptor agonists were shown to have a significant association with lower liver-related mortality. “Currently, lifestyle modification is the main approach to managing [MASLD]; however, utilization of available potentially beneficial medications could also improve patients' outcomes,” said the study authors. They noted that limitations of the review included discrepancies among the studies, and they called for long-term prospective studies to confirm the findings.

A retrospective cohort study, published by JAMA Internal Medicine on Sept. 16, compared GLP-1 receptor agonists with DPP-4 inhibitors in patients with diabetes and MASLD using Veterans Affairs data. The 16,058 patients who started a GLP-1 receptor agonist (14,606 without cirrhosis at baseline) were propensity score matched 1:1 to patients who initiated a DPP-4 inhibitor during the same month. In patients without cirrhosis at baseline, GLP-1 receptor agonist use was associated with a lower risk of developing cirrhosis (9.98 vs. 11.10 events per 1,000 person-years; hazard ratio [HR], 0.86 [95% CI, 0.75 to 0.98]). GLP-1 patients also had a lower risk of the composite outcome of cirrhosis complications (1.89 vs. 2.55 events per 1,000 person-years; HR, 0.78 [95% CI, 0.59 to 1.04]) and mortality (21.77 vs. 24.43 events per 1,000 person-years; HR, 0.89 [95% CI, 0.81 to 0.98]). In patients with cirrhosis, there were no significant differences between groups. “These data highlight the potential consequences of delaying treatment—either by lack of access or by patient or health care professional choice—on subsequent risk of cirrhosis complications,” said the study authors. “These results support the need for long-term randomized clinical trials to test the benefits of GLP-1 [receptor agonist] use for primary prevention of cirrhosis in patients with MASLD.” Limitations include the risk of confounding and the small number of certain events, including hepatocellular cancer.

Finally, a study published by PLoS One on Sept. 27 compared MASLD screening strategies among patients with type 2 diabetes. The researchers developed the BIMAST Score, based on aspartate aminotransferase levels and body mass index, and compared it to five other screening strategies: ultrasound plus abnormal liver function tests, the FIB-4 score, the NAFLD fibrosis score, enhanced liver fibrosis (ELF), and transient elastography. The study included 300 patients, 64% with MASLD and 10% with other causes of liver disease. Overall, 17% of patients had significant fibrosis due to MASLD, while 11% had advanced fibrosis and 3% had cirrhosis. The BIMAST Score was found to perform better than the other noninvasive strategies and had a lower false-negative rate at 10% versus 54% with ELF and 38% with FIB-4. It also proved to be cost-effective. The study authors noted that given rising concern about MASLD, “primary care physicians demand a clearly defined, pragmatical referral management pathway, which can easily be implemented in high-risk groups in the community.” They called for the BIMAST Score to be tested and then “included in the holistic assessment of diabetic patients.”