Related Experiment Video

Updated: Jun 24, 2026

Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis (NASH) Resolution
04:14

Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis (NASH) Resolution

Published on: April 16, 2019

Glucagon-Like Peptide-1 Receptor Agonists and Incident Major Adverse Liver Outcomes in People With Type 2 Diabetes

Gregor A Maier1, Ramon A Hofmann1, Michael Roden2,3,4

  • 1Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.

Diabetes, Obesity & Metabolism
|June 22, 2026
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce major adverse liver outcomes (MALO) and cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes compared to SGLT-2 inhibitors.

Area of Science:

  • Hepatology and Endocrinology
  • Pharmacological Interventions for Metabolic Diseases

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) treatment options are limited.
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve cardiovascular health.
  • Comparative effectiveness of GLP-1 RAs versus SGLT-2 inhibitors on liver outcomes in MASLD is not well-established.

Purpose of the Study:

  • To compare the effectiveness of GLP-1 RAs against SGLT-2 inhibitors.
  • To evaluate the impact on major adverse liver outcomes (MALO), liver cirrhosis, and all-cause mortality.
  • To assess outcomes in patients with MASLD and type 2 diabetes.

Main Methods:

  • Utilized German claims data (2005-2024) for an active comparator, new-user cohort study.
  • Included 45,256 patients with MASLD and type 2 diabetes, comparing 9,993 GLP-1 RA users to 35,263 SGLT-2 inhibitor users.
  • Employed weighted Cox proportional hazard models to estimate hazard ratios (HR) for MALO, liver cirrhosis, and mortality.

Main Results:

  • GLP-1 RA users showed a trend towards lower hazard of MALO (HR 0.91) compared to SGLT-2 inhibitor users over median 4.3 years.
  • On-treatment analysis suggested a stronger association with reduced MALO (HR 0.78).
  • GLP-1 RAs were associated with lower hazards for liver cirrhosis (HR 0.88), decompensation events (HR 0.91), and hepatocellular carcinoma (HCC) (HR 0.76), but not all-cause mortality (HR 1.04).

Conclusions:

  • GLP-1 RAs demonstrated a potential therapeutic advantage for liver-specific outcomes in patients with MASLD and type 2 diabetes.
  • A lower hazard for incident MALO and liver cirrhosis was observed with GLP-1 RAs compared to SGLT-2 inhibitors.
  • Further research may elucidate the role of GLP-1 RAs in managing liver disease progression in this patient population.
Keywords:
antidiabetic drugeffectivenessfatty liver diseaseobservational studypharmaco‐epidemiology

More Related Videos

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis08:58

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis

Published on: March 11, 2017

An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes10:17

An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes

Published on: April 26, 2019

Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood glucose levels...
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively manages...
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are typically...
Type II Diabetes II: Pathophysiology01:24

Type II Diabetes II: Pathophysiology

PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.