Treatment of Type 2 Diabetes in Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) with Overweight or Obesity

Adults with type 2 diabetes who also have metabolic dysfunction–associated steatotic liver disease (MASLD) — including those with biopsy-proven metabolic dysfunction–associated steatohepatitis (MASH) or at high risk for liver fibrosis based on noninvasive tests — and concurrent overweight or obesity represent a distinct clinical population in which glycemic agent selection requires careful attention to hepatic effects.

Clinical scenario: Type 2 diabetes co-occurring with metabolic dysfunction–associated steatotic liver disease (MASLD) — including biopsy-proven MASH or high fibrosis risk — in a patient with overweight or obesity.

Treatment approach

In this scenario, glucose-lowering therapy selection is guided by the specific hepatic phenotype. A preferred class of agent with demonstrated benefits in MASH is identified, alongside alternatives with potential hepatic benefit. Combination strategies and a distinct approach for advanced liver disease are also addressed — details are in the full protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.2337/dc26-S009

In adults with type 2 diabetes, metabolic dysfunction–associated steatotic liver disease (MASLD), and overweight or obesity, consider using a GLP-1 RA with demonstrated benefits in metabolic dysfunction–associated steatohepatitis (MASH) or a dual GIP and GLP-1 RA with potential benefits in MASH for glycemic management and as an adjunctive therapy to interventions for weight loss.

In adults with type 2 diabetes and biopsy-proven MASH or those at high risk for liver fibrosis (based on noninvasive tests), a GLP-1 RA is preferred for glycemic management due to beneficial effects on MASH.

Pioglitazone or a dual GIP and GLP-1 RA can be considered for glycemic management due to potential beneficial effects on MASH.

Combination therapy with pioglitazone plus a GLP-1 RA can be considered for the treatment of hyperglycemia in adults with type 2 diabetes with biopsy-proven MASH or those at high risk of liver fibrosis (identified with noninvasive tests) due to potential beneficial effects on MASH.

Use insulin in the setting of decompensated cirrhosis.

View source ↗