As the prevalence of type 2 diabetes and liver disease continues to increase, so too does the awareness of the bidirectional relationship between these two diseases. Endocrine News speaks to Priyanka Majety, MD, about her recent paper detailing this relationship, and how endocrinologists are uniquely positioned to break the cycle.
In her practice, Priyanka Majety, MD, mostly treats patients with obesity and type 2 diabetes. She’s assistant professor of Endocrinology, Diabetes, and Metabolism at Virginia Commonwealth University (VCU) and the adult outpatient diabetes director for the VCU Health System, so her patients are in good hands. But she has noticed a concerning – and growing — trend around the clinic.
“In practice, I increasingly saw patients where type 2 diabetes and fatty liver disease weren’t just comorbidities – they were interacting in complex, cyclical ways,” she says.
Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) affects about 30% of the population globally, while type 2 diabetes affects around 70%, with both increasing worldwide. They’re both growing in prevalence, and what’s worse, both diseases appear to feed off each other.
“Insulin resistance is central: it promotes hepatic fat accumulation, oxidative stress, and inflammation, which in turn worsen insulin resistance, creating a self-perpetuating, or ‘vicious’ cycle,” Majety says. “MASLD worsens glycemic control by contributing to systemic insulin resistance and altering glucose metabolism. This interplay not only accelerates liver disease progression but also increases the risk of cardiovascular and kidney complications.”
Motivated by these clinical insights, Majety and her co-authors recently published a narrative review in Endocrines titled “Current and Emerging Treatments for Metabolic Associated Steatotic Liver Disease (MASLD) and Diabetes: A Narrative Review.”
“This review was born out of both clinical necessity and scientific curiosity,” Majety says. “With MASLD now recognized as the most common chronic liver disease worldwide, and type 2 diabetes being one of its strongest risk factors and consequences, I felt we needed a comprehensive synthesis.”
The article aims to distill the emerging science and therapeutic strategies that address this intricate relationship – an analysis of recent evidence, especially around GLP-1 receptor agonists (GLP-1Ras), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and dual incretin therapies, and collaboration with co-authors who brought hepatology, cardiology, and metabolic expertise.
“This review comes at a pivotal moment: with the redefinition of MASLD and the emergence of medications that address both hepatic and glycemic endpoints, it’s crucial that clinicians stay informed on how best to screen, diagnose, and manage these overlapping conditions,” Majety says.
Empowering Patients
Majety says that liver disease is not monolithic, but rather a heterogeneous disease with complex, overlapping pathways. Some patients have predominantly steatosis, while others have progressive fibrosis. And the underlying drivers — insulin resistance, inflammation, oxidative stress, de novo lipogenesis, genetics — can vary.
Majety goes on to say that the future of MASLD therapy lies in precision medicine: using noninvasive biomarkers, genetic risk scores, or metabolic phenotyping to tailor treatments. According to Majety, this precision medicine approach is essential for developing new, more effective treatments and for optimizing outcomes in clinical practice. Understanding which pathways are dominant in a given patient will help us choose between incretins, PPAR agonists, or anti-fibrotic agents.
“Insulin resistance is central: it promotes hepatic fat accumulation, oxidative stress, and inflammation, which in turn worsen insulin resistance, creating a self-perpetuating, or ‘vicious’ cycle. MASLD worsens glycemic control by contributing to systemic insulin resistance and altering glucose metabolism. This interplay not only accelerates liver disease progression but also increases the risk of cardiovascular and kidney complications.” – Priyanka Majety, MD, assistant professor, Endocrinology, Diabetes, and Metabolism, Virginia Commonwealth University, Richmond, Virginia
“Individualized care is central to both diabetes and MASLD management,” Majety says. “Some patients may benefit most from weight-centric therapies, others from insulin sensitizers, and still others from cardiovascular risk management strategies such as lipid-lowering agents. The article underscores that clinicians should assess disease severity, comorbidities, and patient preferences when choosing therapies. Tailoring treatment plans not only improves outcomes but also empowers patients.”
Powerful Adjunct
The first line of treatment in these plans is usually lifestyle change, and for Majety, lifestyle change should remain a cornerstone even if that treatment plan includes pharmacotherapy. But she points out that life is complicated and can get in the way sometimes, and sustainability can be challenging, especially in patients with chronic conditions like long-standing insulin resistance, advanced fibrosis, or multiple comorbidities.
“There are socioeconomic, behavioral barriers and underlying genetic/metabolic drivers that limit lifestyle changes alone,” Majety says. “Pharmacotherapy provides a powerful adjunct. Agents like GLP-1RAs and pioglitazone can improve insulin sensitivity and hepatic histology, while newer incretin-based therapies offer dual metabolic and hepatic benefits. In patients unable to achieve durable improvements through lifestyle alone, medications offer a bridge and sometimes a breakthrough.”
Majety says that GLP-1Ras and the dual GLP1-GIP agonists have been especially transformative. “I’ve seen patients with obesity, poorly controlled diabetes, and steatosis on imaging show both improved A1C and significant improvement in liver function tests after several months of therapy,” she says. “In select patients, pioglitazone has also been helpful.”
Breaking the Cycle
As the prevalence of MASLD grows, so too does its toll on people’s wallets. The authors point out that the most chronic liver disease in the world costs the U.S. more than $100 billion annually. There is currently only one FDA approved treatment for it.
But as for this bidirectional relationship between MASLD and type 2 diabetes, endocrinologists are uniquely positioned to interrupt this loop, break this vicious cycle. “We are the key to early identification of these patients with metabolic risk factors,” Majety says. “We manage the metabolic drivers and prescribe insulin-sensitizing agents and other medications that improve both glycemic and hepatic endpoints.”
For Majety, she starts with a comprehensive assessment, evaluating metabolic risk factors, degree of liver involvement and comorbidities screening her patients with diabetes for liver disease using the FIB4 calculator. “I emphasize the importance of lifestyle changes that are sustainable and encourage physical activity,” she says. “I rely on our certified diabetes care and education specialist. I try to initiate/optimize metabolic therapy with agents that can address both liver and glucose control. If they are to start GLP1RA or dual GLP-GIP, I emphasize the importance of protein intake and strength training. And finally, I refer them to hepatology for their expertise.”
“If the patients have advanced cirrhosis, I focus on the prevention of hypoglycemia. This needs frequent adjusting of insulin, using technology to our advantage and dietary counseling,” Majety continues.
Majety tells Endocrine News that what attracted her to endocrinology was the intricate interplay between hormones and every organ system, and the opportunity to impact chronic diseases like diabetes and other conditions that profoundly affect quality of life. “Endocrinology uniquely blends intellectual stimulation with emotional satisfaction, especially through patient education and counseling, which can be incredibly empowering and rewarding,” she says.
This intricate interplay between MASLD and type 2 diabetes has been a learning experience for Majety as well, she says. But she again speaks to the importance of learning, of education. “Educating and empowering the patients is crucial,” Majety says. “Shared decision making improves adherence and outcomes.”
Loading ...