As incretin-based therapies and metabolic pharmacology become more embedded in everyday care, gastroenterologists are encountering new challenges—and new opportunities. GLP-1 receptor agonists (GLP-1RAs), tirzepatide, which is a combined GLP-RA and glucose-dependent insulinotropic polypeptide (GIP) agonist, and sodium-glucose co-transporter-2 (SGLT2) inhibitors, once viewed as the remit of diabetologists, are now shaping how we approach common GI symptoms, endoscopic safety, and liver disease management.

Two recent Frontline Gastroenterology publications—Lisa Sharkey’s review on anti-obesity medications and the article by Isaacs et al. on metabolic dysfunction–associated steatotic liver disease (MASLD) pharmacotherapy—highlight these developments clearly. But beyond summarising their findings, it is worth reflecting on how they signal a broader shift in our specialty.

GLP-1RAs in Practice: Familiar Symptoms, New Mechanisms

GLP-1RAs are now widely prescribed for obesity and type 2 diabetes and increasingly in the context of liver disease. As detailed in Sharkey’s review, gastrointestinal symptom prevalence is high—nausea (15-59%), vomiting (5-20%), constipation (4-37%), and diarrhoea (5-25%). These effects are physiologically predictable, driven by delayed gastric emptying and altered intestinal motility.

In practice, however, distinguishing these drug-related effects from primary GI disease can be challenging. I’ve seen several patients referred for investigation of new-onset dyspepsia or constipation, only to find that symptoms followed a recent dose escalation of semaglutide or liraglutide.

The article’s practical recommendations—focusing on dietary adjustment, trial withdrawal or dose reduction, and selective use of prokinetics—are highly relevant. In particular, Sharkey’s discussion around pre-endoscopy safety stands out. Reports of retained gastric contents despite adequate fasting highlight the need for pre-procedure screening protocols, especially in symptomatic patients.

This is something I’ve begun to notice in endoscopy units as well: patients attending for gastroscopy or colonoscopy are increasingly on weekly injectable therapies, and our standard “fasting for six hours” guidance may no longer be sufficient. It’s a subtle shift, but one that has clear implications for service safety and workflow.

MASLD: A New Era of Liver Pharmacotherapy

MASLD (formerly NAFLD) now affects over half of people with type 2 diabetes. For many years, we offered lifestyle advice and monitored fibrosis progression, but pharmacological treatment options were limited. That picture is changing.

As Isaacs et al. summarise, there is now growing evidence to support the use of GLP-1RAs, tirzepatide, and SGLT2 inhibitors in managing hepatic steatosis, inflammation, and even fibrosis:

• Semaglutide (ESSENCE trial): MASH resolution in 63% of patients; fibrosis improvement in 37%.
• Tirzepatide (SYNERGY-NASH): MASH resolution in 62%; fibrosis regression in 51%.
• SGLT2 inhibitors: Benefit on liver fat and stiffness on imaging, though biopsy-confirmed fibrosis data remain limited.
• Pioglitazone: Longstanding evidence for histological improvement in MASH, with tolerability concerns.

This data reinforces a message we are hearing more often in MDTs and guidelines: MASLD should not be passively monitored when pharmacotherapy can meaningfully alter outcomes. For gastroenterologists, this means developing confidence in the metabolic agents now central to liver care—even if they originate from outside our traditional therapeutic toolkit.

Personally, I’ve found that my comfort with these therapies has grown primarily through shared care with endocrinology and hepatology colleagues. But these interactions also highlight how central our role can—and arguably should—become in initiating and monitoring these treatments, especially in patients presenting to GI clinics or liver services.

How Our Practice Is Changing

What’s striking is how the use of these therapies is beginning to influence multiple areas of gastroenterology, often in subtle but important ways:

1. Outpatient Clinics

Patients now regularly present with GLP-1RA-associated symptoms. A careful medication history—particularly around dose initiation or escalation—is essential and can often prevent unnecessary investigation.

2. Endoscopy Practice

Pre-procedure assessment increasingly requires attention to GLP-1RA use, especially in symptomatic patients undergoing upper GI endoscopy with sedation. Some units are beginning to develop local policies around when to withhold therapy or consider additional fasting guidance.

3. Inpatient Consultations

On-call gastroenterology teams are more frequently asked to assess nausea, vomiting, or diarrhoea in patients on GLP-1RAs. Differentiating between medication side effects and organic pathology is becoming a core skill.

4. Liver Disease Management

MASLD has long been managed conservatively. With pharmacotherapy now a viable option, gastroenterologists must be prepared to co-manage treatment decisions—especially in patients without access to tertiary hepatology services.

Reflections on Training and the Road Ahead

From a training perspective, these developments have prompted reflection. While formal teaching on pharmacological management of obesity or MASLD is limited in many gastroenterology programmes, the relevance to routine clinical practice is increasing. There may be scope for more structured exposure to this evolving area—whether through teaching sessions, multidisciplinary clinics, or joint training opportunities with endocrinology and obesity services.

Equally, clinical leadership in this space is not limited to hepatologists or diabetologists. Gastroenterologists—particularly those managing liver disease, functional symptoms, or endoscopy pathways—are well placed to shape how these therapies are implemented safely and effectively.

What’s clear is that this is not a niche concern. These medications are already changing how we approach common GI presentations, prepare for procedures, and advise on liver disease management. Ensuring that we’re equipped with the right knowledge and systems to respond will be increasingly important over the coming years.

Final Thoughts

The widespread use of GLP-1RAs, tirzepatide, and SGLT2 inhibitors is not only improving outcomes in diabetes and obesity—it is reshaping gastroenterology itself.

The recent Frontline Gastroenterology articles and podcasts serve as timely reminders that our specialty must remain adaptable, collaborative, and forward-thinking. Whether managing GI symptoms, advising on liver-directed therapy, or preparing patients for safe endoscopy, we will need to stay informed and engaged.

These therapies represent a new chapter in metabolic gastroenterology—and one that many of us are already writing into our practice.

Read & Listen

• 📰 Anti-obesity drugs for the gastroenterologist – Sharkey
• 📰 Role of anti-diabetic medications in MASLD – Isaacs et al.
• 🎧 GLP-1s & GI symptoms – Podcast
• 🎧 MASLD pharmacotherapy – Podcast

#FGInPractice | #GLP1 | #MASLD | #Endoscopy | #MetabolicGastro | #ObesityCare | #TrainingAndPractice