2026-02-04
Liver, sugar, and pills: who's in control?
Endocrinology and Metabolism
By Ana Espino | Published on February 4, 2026 | 3 min read
MASLD (Metabolic dysfunction-associated steatotic liver disease) refers to the accumulation of fat in the liver associated with metabolic syndrome. It is now recognized as one of the main comorbidities of type 2 diabetes (T2D). Its prevalence reaches nearly 70% in diabetic patients, increasing the risk of progression to fibrosis, cirrhosis, and hepatocellular carcinoma.
Despite this strong association, no validated specific treatment for MASLD currently exists. Current strategies rely on weight loss and glycemic control. Some antidiabetic drugs, such as glitazones or SGLT2 inhibitors, have shown benefits on liver parameters, but the evidence remains inconsistent, mostly derived from isolated trials with heterogeneous endpoints. Moreover, no clear consensus exists regarding the optimal antidiabetic choice in the presence of MASLD, making clinical decision-making challenging.
In this context, the present study was designed to compare the effectiveness of 15 antidiabetic agents on various hepatic and metabolic markers in patients with T2D and MASLD, through a network meta-analysis based on randomized clinical trials.
Twenty-one randomized clinical trials, involving a total of 1,717 participants, were selected. The evaluated treatments included 15 antidiabetic agents, among them: ertugliflozin, empagliflozin, liraglutide, exenatide, pioglitazone, metformin, sitagliptin, and gliclazide. These studies compared the medications to each other or to placebo, with an average intervention duration of 24 weeks. The analysis was conducted using a Bayesian approach, and overall methodological quality revealed a moderate to low risk of bias. Primary endpoints were liver enzymes ALT and AST, and triglycerides. Secondary outcomes included HDL, LDL, fasting blood glucose, HbA1c, BMI, and liver stiffness measurement (LSM).
Among the 15 treatments compared, ertugliflozin emerged as the most effective in reducing hepatic transaminases (ALT and AST). It also showed notable improvement in triglycerides, lipid profile (increased HDL, decreased LDL), as well as a reduction in BMI and liver stiffness (LSM).
Glycemic and HbA1c improvements were observed with ertugliflozin, as well as with the GLP-1 receptor agonists liraglutide and exenatide. Pioglitazone confirmed its positive effect on liver enzymes, although it was associated with weight gain.
MASLD in diabetic patients is a silent but progressive disease, with no approved pharmacological treatment to date. Management remains fragmented, due to the lack of robust comparative data between antidiabetic drug classes. This study aimed to compare the impact of 15 medications on key metabolic and hepatic parameters. It highlights the potential of ertugliflozin, which appears to combine both glycemic efficacy and hepatic improvement.
However, several limitations of this study warrant further investigation. Larger, longer-term clinical trials are needed, with better geographic and ethnic representation, and combined follow-up of liver and metabolic outcomes. The future of care also lies in exploring therapeutic combinations and identifying predictive biomarkers of response to enable truly personalized treatments.
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
MASLD (Metabolic dysfunction-associated steatotic liver disease) refers to the accumulation of fat in the liver associated with metabolic syndrome. It is now recognized as one of the main comorbidities of type 2 diabetes (T2D). Its prevalence reaches nearly 70% in diabetic patients, increasing the risk of progression to fibrosis, cirrhosis, and hepatocellular carcinoma.
Despite this strong association, no validated specific treatment for MASLD currently exists. Current strategies rely on weight loss and glycemic control. Some antidiabetic drugs, such as glitazones or SGLT2 inhibitors, have shown benefits on liver parameters, but the evidence remains inconsistent, mostly derived from isolated trials with heterogeneous endpoints. Moreover, no clear consensus exists regarding the optimal antidiabetic choice in the presence of MASLD, making clinical decision-making challenging.
In this context, the present study was designed to compare the effectiveness of 15 antidiabetic agents on various hepatic and metabolic markers in patients with T2D and MASLD, through a network meta-analysis based on randomized clinical trials.
Ertugliflozin: a rising star for the metabolic fatty liver?
Twenty-one randomized clinical trials, involving a total of 1,717 participants, were selected. The evaluated treatments included 15 antidiabetic agents, among them: ertugliflozin, empagliflozin, liraglutide, exenatide, pioglitazone, metformin, sitagliptin, and gliclazide. These studies compared the medications to each other or to placebo, with an average intervention duration of 24 weeks. The analysis was conducted using a Bayesian approach, and overall methodological quality revealed a moderate to low risk of bias. Primary endpoints were liver enzymes ALT and AST, and triglycerides. Secondary outcomes included HDL, LDL, fasting blood glucose, HbA1c, BMI, and liver stiffness measurement (LSM).
Among the 15 treatments compared, ertugliflozin emerged as the most effective in reducing hepatic transaminases (ALT and AST). It also showed notable improvement in triglycerides, lipid profile (increased HDL, decreased LDL), as well as a reduction in BMI and liver stiffness (LSM).
Glycemic and HbA1c improvements were observed with ertugliflozin, as well as with the GLP-1 receptor agonists liraglutide and exenatide. Pioglitazone confirmed its positive effect on liver enzymes, although it was associated with weight gain.
One treatment for two targets?
MASLD in diabetic patients is a silent but progressive disease, with no approved pharmacological treatment to date. Management remains fragmented, due to the lack of robust comparative data between antidiabetic drug classes. This study aimed to compare the impact of 15 medications on key metabolic and hepatic parameters. It highlights the potential of ertugliflozin, which appears to combine both glycemic efficacy and hepatic improvement.
However, several limitations of this study warrant further investigation. Larger, longer-term clinical trials are needed, with better geographic and ethnic representation, and combined follow-up of liver and metabolic outcomes. The future of care also lies in exploring therapeutic combinations and identifying predictive biomarkers of response to enable truly personalized treatments.
Read next: Could cinnamon become a natural treatment for metabolic syndrome?
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
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