Dec. 12, 2023
The increasing prevalence of obesity, diabetes and other metabolic diseases over the past few decades has a significant impact on patients with gastrointestinal and liver diseases. In a review article published in Hepatology in 2023, lead author Kymberly D. Watt, M.D., a hepatologist at Mayo Clinic in Rochester, Minnesota, and co-authors discuss the role of obesity in the progression of chronic liver disease, and they present a detailed approach to the management of obesity from the hepatology clinic.
"Obesity can pose unique challenges in both nontransplant and transplant hepatology settings," explains Dr. Watt. "Weight loss can improve liver health and overall health, regardless of the type of liver disease diagnosed. Aggressive weight management is a critical tool in our efforts to help mitigate disease progression and major adverse liver and cardiovascular outcomes in obese patients with liver disease. This includes type 2 diabetes or prediabetes and the associated cardiovascular risk factors, all of which are more likely to lead to mortality than the GI or liver disease."
In this e-newsletter article, Dr. Watt summarizes some of the research findings related to the use of dietary supplements marketed for weight loss; anti-obesity medications, including glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors; and bariatric surgery.
Dietary supplements marketed for weight loss
Dr. Watt and co-authors acknowledge that a full review of dietary supplements is beyond the scope of their article, and they point out that the effectiveness of the majority of these compounds remains to be determined. Additionally, some of these supplements have been associated with liver toxicity.
Anti-obesity medications
Ample research data has demonstrated the effectiveness of these medications, including orlistat, phentermine and topiramate, and naltrexone and bupropion in helping patients lose weight. But Dr. Watt notes that it's important to be aware that data related to long-term use of these medications is scarce and that immunosuppressive medications have the potential to interact with orlistat.
- Glucagon-like peptide 1 (GLP-1) receptor agonists. These agents can lead to significant weight loss. According to Dr. Watt, developing a solid understanding of how the various GLP-1 receptor agonists differ from one another may help clinicians choose the most appropriate agent for an individual patient. The Hepatology article contains a detailed discussion about these medications. Key research findings about GLP-1 receptor agonists include the following:
- Treatment with liraglutide, exenatide or dulaglutide is associated with reduced transaminases, intrahepatic adipose and visceral fat. A phase 2 multinational clinical trial of semaglutide demonstrated that this drug improves individual histological features of metabolic dysfunction-associated steatohepatitis (MASH).
- GLP-1 receptor agonists also have multiple beneficial metabolic effects, including improvements in insulin resistance, hypertension and cardiovascular disease.
- In patients with alcohol use disorder, GLP-1 receptor agonists also can reduce alcohol craving and intake.
- Combinations of GLP-1 receptor agonists and glucose-dependent insulinotropic polypeptide receptor agonists have been shown to benefit patients with steatotic liver disease (SLD), but more data is needed.
- Sodium-glucose cotransporter-2 (SGLT-2) inhibitors. These medications are used to treat maladaptive glucose reabsorption in patients with type 2 diabetes. Recent clinical trials suggest they may be effective as a treatment for SLD. Weight loss associated with SGLT-2 inhibitor use is more modest than weight loss associated with GLP-1 receptor agonists or dual GLP-1/gastric inhibitory polypeptide (GIP) compounds. SGLT-2 inhibitors are associated with improvements in metabolic flexibility and fatty acid oxidation and positive effects on cardiovascular disease, diastolic heart failure and renal function.
Bariatric surgery
According to Dr. Watt and co-authors, multiple studies have established that with careful patient selection and timing, bariatric surgery can be an effective tool for achieving and maintaining weight loss and metabolic improvement in patients with obesity and chronic liver disease, especially in individuals with SLD. Key points related to bariatric surgery include the following:
- Sleeve gastroplasty (SG), whether endoscopic or surgical, improves steatosis and markers of fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, more data focused on liver-specific outcomes is needed.
- In patients with advanced liver disease who undergo bariatric surgery, outcome data is less well established. In select patients, bariatric surgery has resulted in long-term weight loss and improved metabolic comorbidities. SG is associated with shorter operative times and preservation of the gastrointestinal tract, which may be required to facilitate future liver transplantation, biliary reconstruction and access for future endoscopic procedures.
- SG can be performed in patients with end-stage liver disease before (if well compensated), simultaneously or after liver transplantation. Optimal timing remains unclear.
- In contrast with the Roux-en-Y gastric bypass procedure, SG does not affect the absorption of immunosuppressants after liver transplantation.
"Overall, the majority of published data suggests that bariatric surgery, especially sleeve gastrectomy, can be considered for carefully selected obese patients before, during or after liver transplantation to promote weight loss and address metabolic comorbidities," says Dr. Watt.
For more information
Watt KD, et al. Obesity management for the hepatologist — what to do, how to do it and why. Hepatology. In press.
Refer a patient to Mayo Clinic.