Proton Pump Inhibitors in Detail: Peptic Ulcers, GORD, H. pylori & Choosing the Right PPI

PPIs: A Drug Class That Changed Gastroenterology

When omeprazole came to market in the late 1980s, it changed the management of acid-related conditions profoundly. Before PPIs, peptic ulcer disease was a relapsing, often debilitating condition — treated repeatedly but rarely cured. H. pylori had barely been recognised as a primary cause. H2 receptor antagonists were the best available option, and they were frequently inadequate.

Today, PPIs are among the most widely prescribed medicines in the world. In the UK, they are available generically at low cost, and low-dose versions are available over the counter for short-term use. This article looks in detail at where PPIs earn their place: peptic ulcer disease, NSAID-induced ulcers, Helicobacter pylori eradication, and GORD — covering treatment duration, agent selection, and what the long-term evidence actually shows.

Peptic Ulcer Disease

A peptic ulcer is an erosion of the stomach lining (gastric ulcer) or the upper small intestine (duodenal ulcer). The causes include H. pylori infection, long-term NSAID use, and — less commonly — conditions such as Zollinger-Ellison syndrome. In the past, the most common treatment was acid suppression with H2 blockers. PPIs have now superseded these for most presentations.

PPI treatment duration for peptic ulcers

NICE recommends the following treatment periods for uncomplicated peptic ulcer disease:

• Duodenal ulcers (H. pylori negative, no NSAID use): 4 weeks of full-dose PPI
• Gastric ulcers (H. pylori negative, no NSAID use): 8 weeks of full-dose PPI
• NSAID-associated ulcers: 8 weeks of PPI — and the NSAID should ideally be stopped or substituted
• H. pylori-positive ulcers: Eradication therapy (7 days), followed by continued PPI for a further 3 weeks where appropriate

NSAID-Induced Ulcers

NSAIDs (non-steroidal anti-inflammatory drugs) — including ibuprofen, naproxen, diclofenac, and aspirin — are one of the most common causes of peptic ulcer disease. They work by inhibiting prostaglandin synthesis, which is responsible for maintaining the protective mucous layer of the gastric lining. Long-term or high-dose NSAID use exposes the gastric mucosa to acid-induced damage.

Studies show that up to 25% of long-term NSAID users develop a peptic ulcer, and the risk is significantly higher in older adults. PPIs are the treatment of choice for both healing NSAID-induced ulcers and preventing their recurrence when NSAIDs must be continued.

Who should receive gastroprotection with NSAIDs?

• Adults aged 65 or over taking regular NSAIDs
• Anyone with a previous peptic ulcer or GI bleeding history
• Patients taking anticoagulants, antiplatelets, corticosteroids, or SSRIs alongside NSAIDs
• Patients with significant comorbidities requiring long-term NSAID treatment

H. pylori Eradication

Helicobacter pylori is a gram-negative bacterium that colonises the gastric mucosa and is responsible for the majority of peptic ulcer disease worldwide. Eradicating it leads to ulcer healing, reduces the risk of relapse significantly, and — for gastric ulcers — reduces the long-term risk of gastric cancer.

First-line eradication therapy (triple therapy)

Current NICE guidance recommends a 7-day course of triple therapy:

All five licensed PPIs can be used in eradication regimens — the choice depends on availability, local resistance patterns, and any drug interactions with concurrent medications.

GORD: Maintenance and Step-Down Therapy

For GORD, PPI use follows a structured approach that balances effective symptom control with the principle of using the lowest effective dose for the shortest necessary duration.

Initial treatment and maintenance

NICE recommends a 4–8 week course of full-dose PPI as initial treatment for GORD with oesophagitis. After successful initial treatment, the options are:

• Step-down to a lower PPI dose — suitable for most patients after 4–8 weeks
• On-demand therapy — taking a PPI only when symptoms occur, for patients with mild or intermittent symptoms
• Continuous maintenance therapy — for patients with severe oesophagitis, Barrett’s oesophagus, or those who relapse quickly after stopping treatment

Stopping PPIs

PPIs should not be stopped abruptly in patients who have been taking them long-term. Rebound acid hypersecretion — a temporary increase in acid production following PPI withdrawal — can cause a return of symptoms and lead patients to restart treatment prematurely. Gradual dose reduction or switching to an H2 blocker for a period is a recognised step-down strategy. For more on this, see our PPI FAQ guide.

Choosing the Right PPI

Five PPIs are licensed for use in the UK: omeprazole, lansoprazole, esomeprazole, pantoprazole, and rabeprazole. All share the same mechanism of action and all achieve substantial acid suppression. Head-to-head clinical trials have generally shown modest differences in efficacy at equivalent doses — and NICE guidance explicitly states that a class effect should be assumed.

For most patients, omeprazole or lansoprazole is the appropriate first choice — both are well evidenced, widely available, and low cost. The choice between them often comes down to patient preference (one is a capsule, one is a dispersible tablet) or concurrent medicines. Compare all three options in our full comparison guide.

NICE Guidance on Choosing Between PPIs

NICE’s position on PPI selection is clear and evidence-based. The Guideline Development Group for CG184 concluded:

• There is no evidence of a clinically significant difference in effectiveness between licensed PPIs when used at equivalent doses
• A class effect should be assumed across all PPIs
• The choice of PPI should be based on clinical circumstances, licensed indications, drug interaction profiles, and cost
• Switching between PPIs is acceptable and may be appropriate if a patient does not respond to or does not tolerate their initial agent

Long-Term PPI Use: Risks and Review

PPIs have an excellent safety profile for short- and medium-term use. However, long-term use — particularly beyond 12 months — is associated with a number of potential adverse effects that warrant monitoring and periodic review.

• Hypomagnesaemia (low magnesium) — particularly with long-term high-dose use; can cause muscle cramps, cardiac arrhythmias
• Increased risk of Clostridium difficile infection — especially in hospitalised or immunocompromised patients
• Modest increase in fracture risk — primarily hip, wrist, and spine; most relevant in older adults and those with osteoporosis
• Vitamin B12 deficiency — reduced gastric acid impairs B12 absorption from food over time
• Potential increased susceptibility to respiratory and gastric infections

NICE recommends that long-term PPI use is reviewed at least annually. The principle is always to use the lowest effective dose and, where appropriate, to attempt step-down or cessation of treatment.