GLP-1/GIP medicines, including semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro), are increasingly prescribed for type 2 diabetes and weight management in the UK. These treatments work by mimicking natural incretin hormones that regulate blood glucose and appetite. Whilst highly effective, emerging clinical interest focuses on their potential indirect effects on vitamin B12 status. Understanding the relationship between GLP-1/GIP therapy and B12 is essential, as deficiency can cause irreversible neurological damage and anaemia. This article examines how these medicines may influence B12 levels, why adequate B12 matters during treatment, and practical strategies for monitoring and maintaining optimal vitamin status.

What Are GLP-1/GIP Medicines and How Do They Work?

GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are naturally occurring incretin hormones that play crucial roles in regulating blood glucose levels and appetite. Medicines that mimic or enhance these hormones have become increasingly important in managing type 2 diabetes and, more recently, obesity.

GLP-1 receptor agonists work by binding to GLP-1 receptors throughout the body, particularly in the pancreas, brain, and gastrointestinal tract. Their primary mechanisms of action include:

• Stimulating insulin secretion in a glucose-dependent manner (reducing hypoglycaemia risk)

• Suppressing glucagon release when blood glucose is elevated

• Slowing gastric emptying, which prolongs satiety

• Acting on appetite centres in the brain to reduce food intake

Common GLP-1 medicines available in the UK include semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), and dulaglutide (Trulicity). These are typically administered via subcutaneous injection weekly or daily, depending on the formulation.

Dual GLP-1/GIP receptor agonists represent a newer therapeutic class. Tirzepatide (Mounjaro) is the first approved medicine in this category, combining the actions of both incretin hormones. GIP contributes additional metabolic benefits, including enhanced insulin secretion and improved lipid metabolism. Clinical trials (SURPASS and SURMOUNT programmes) have shown that dual agonists may offer improved glycaemic control and weight reduction compared to GLP-1 monotherapy.

These medicines are prescribed according to NICE guidance. For type 2 diabetes (NICE NG28), they are typically used when patients have not achieved adequate control with metformin and lifestyle modifications. For weight management, specific criteria apply as outlined in relevant NICE technology appraisals (such as TA875 for semaglutide 2.4mg), generally requiring a BMI ≥35 kg/m² (or ≥30 kg/m² with weight-related comorbidities), with lower thresholds (typically 2.5 kg/m² lower) for people from certain ethnic groups, and treatment within specialist weight management services.

The Link Between GLP-1/GIP Treatments and Vitamin B12

The relationship between GLP-1/GIP medicines and vitamin B12 status is an emerging area of clinical interest, though there is no official direct pharmacological link established between these therapies and B12 deficiency. However, several indirect mechanisms may influence B12 levels in patients using these treatments.

The primary concern relates to the gastrointestinal effects of GLP-1/GIP medicines. These drugs slow gastric emptying and alter gut motility, which are fundamental to their therapeutic action, although these effects may diminish somewhat over time. Vitamin B12 absorption is a complex process requiring adequate stomach acid, intrinsic factor (produced by gastric parietal cells), and proper function of the terminal ileum. Any disruption to gastric physiology or transit time could theoretically affect this intricate absorption pathway.

Additionally, many patients prescribed GLP-1/GIP medicines are already taking metformin for type 2 diabetes management. Metformin is well-established as reducing B12 absorption, primarily through interference with calcium-dependent B12-intrinsic factor uptake in the terminal ileum. The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a Drug Safety Update recommending periodic B12 monitoring in patients on long-term metformin therapy.

Dietary changes associated with GLP-1/GIP treatment may also contribute to reduced B12 intake. These medicines often cause significant appetite suppression and early satiety, leading to substantially reduced food consumption—the intended therapeutic effect for weight management. Patients may inadvertently consume less B12-rich foods such as meat, fish, dairy products, and fortified cereals.

Other risk factors for B12 deficiency that may coexist include proton pump inhibitor or H2-antagonist use, vegan/vegetarian diets, previous bariatric surgery, pernicious anaemia, and other malabsorptive conditions. Those experiencing persistent nausea or food aversions, common side effects of these medicines, may further restrict their dietary variety, potentially compromising micronutrient intake including B12.

Why Vitamin B12 Matters When Taking GLP-1/GIP Medicines

Vitamin B12 (cobalamin) is essential for numerous critical physiological processes, making adequate levels particularly important for patients undergoing metabolic treatments. This water-soluble vitamin serves as a cofactor for only two enzymes in human metabolism, but both are vital: methionine synthase (involved in DNA synthesis and methylation) and methylmalonyl-CoA mutase (essential for fatty acid metabolism and energy production).

Neurological function depends heavily on adequate B12 status. The vitamin is crucial for myelin synthesis, the protective sheath surrounding nerve fibres. Deficiency can lead to demyelination, resulting in peripheral neuropathy, balance problems, cognitive impairment, and in severe cases, subacute combined degeneration of the spinal cord. For patients with type 2 diabetes, who already face increased risk of diabetic neuropathy, maintaining optimal B12 levels is particularly important to avoid compounding neurological complications.

Haematological health requires sufficient B12 for red blood cell production. Deficiency causes megaloblastic anaemia, characterised by large, immature red blood cells that function poorly. Symptoms include fatigue, weakness, shortness of breath, and pallor—effects that could significantly impact quality of life and may be mistakenly attributed to other causes in patients managing multiple health conditions.

The irreversible nature of some B12 deficiency complications underscores the importance of prevention and early detection. Whilst anaemia typically resolves with B12 replacement, neurological damage may be permanent if deficiency remains untreated for extended periods. According to NHS guidance, neurological symptoms can occur even without anaemia, and the severity of symptoms does not always correlate with B12 levels.

Importantly, if B12 deficiency is suspected, especially with neurological symptoms, treatment should not be delayed. Additionally, folate deficiency should not be treated in isolation until B12 deficiency has been excluded or treated, as this could worsen neurological damage.

For patients taking GLP-1/GIP medicines—particularly those on concurrent metformin, following restricted diets, or with pre-existing malabsorption conditions—proactive monitoring and management of B12 status should be considered an integral component of comprehensive care.

Signs of B12 Deficiency During GLP-1/GIP Treatment

Recognising B12 deficiency can be challenging because symptoms often develop gradually and may be non-specific, particularly in patients managing diabetes or obesity who may attribute these symptoms to their underlying conditions or weight loss efforts. Healthcare professionals and patients should maintain awareness of potential indicators.

Neurological manifestations are among the most concerning signs:

• Paraesthesia (pins and needles) in hands and feet

• Numbness or altered sensation in extremities

• Difficulty with balance or coordination

• Memory problems or difficulty concentrating

• Mood changes, including depression or irritability

• Visual disturbances in rare cases

These symptoms may be particularly difficult to distinguish from diabetic neuropathy, making objective assessment through blood testing essential rather than relying solely on clinical presentation.

Haematological and general symptoms include:

• Persistent fatigue or weakness disproportionate to weight loss

• Shortness of breath on minimal exertion

• Palpitations or rapid heart rate

• Pale or jaundiced appearance

• Glossitis (sore, red tongue) or mouth ulcers

• Unexplained decline in appetite (beyond expected GLP-1/GIP effects)

Urgent medical attention is required for:

• New or progressive neurological deficits

• Ataxia (problems with coordination and balance)

• Visual changes

• Severe anaemia or cardiovascular symptoms

• Any B12 deficiency symptoms during pregnancy

Patients should contact their GP if they experience:

• New or worsening neurological symptoms, particularly sensory changes

• Persistent extreme fatigue affecting daily activities

• Unexplained cognitive changes or memory problems

• Symptoms of anaemia

It is important to note that B12 deficiency can exist without obvious symptoms, particularly in early stages. NICE guidance on metformin use recommends measuring B12 levels in patients with symptoms suggestive of deficiency. A similar approach may be prudent for patients on GLP-1/GIP medicines, especially those with additional risk factors such as vegan diets, previous gastric surgery, or concurrent metformin use. UK investigations typically include full blood count, serum B12, and holotranscobalamin (active B12) where available; methylmalonic acid may be considered if results are equivocal.

Managing B12 Levels While Using GLP-1/GIP Therapy

Proactive management of vitamin B12 status should be integrated into the care pathway for patients prescribed GLP-1/GIP medicines, particularly those with additional risk factors for deficiency. A comprehensive approach encompasses baseline assessment, monitoring, dietary optimisation, and supplementation when indicated.

Baseline and ongoing monitoring:

Before initiating GLP-1/GIP therapy, consider measuring baseline B12 levels, particularly in patients concurrently taking metformin, those with previous bariatric surgery, individuals following plant-based diets, or those with malabsorption conditions. Whilst there is no universal guidance mandating routine B12 monitoring specifically for GLP-1/GIP users, clinical judgement should guide individualised monitoring. For metformin users, the MHRA recommends periodic monitoring, especially in those with symptoms suggestive of B12 deficiency.

Dietary strategies to maintain B12 intake:

Despite reduced appetite, patients should be encouraged to prioritise nutrient-dense foods. Excellent B12 sources include:

• Meat, particularly liver and kidney

• Fish, especially salmon, trout, and tuna

• Dairy products including milk, cheese, and yoghurt

• Eggs

• Fortified breakfast cereals and nutritional yeast (for vegetarians/vegans)

Referral to a registered dietitian can help patients develop eating strategies that accommodate reduced appetite whilst ensuring adequate micronutrient intake.

Supplementation approaches:

For confirmed deficiency, treatment depends on severity and underlying cause. NHS and BNF recommendations typically include:

• Oral cyanocobalamin 50–150 micrograms daily for dietary deficiency

• Intramuscular hydroxocobalamin for malabsorption or neurological involvement (initially 1 mg every other day for 1-2 weeks for neurological symptoms, or 1 mg 3 times weekly for 2 weeks without neurological symptoms; followed by maintenance doses of 1 mg every 2-3 months)

Importantly, if neurological symptoms are present, treatment should be started urgently and not delayed for test results. Patients without confirmed deficiency but with risk factors may benefit from prophylactic oral B12 supplementation (typically 50–150 micrograms daily), though this should be discussed with their healthcare provider rather than self-initiated.

Patient safety and follow-up:

Patients should be educated about deficiency symptoms and encouraged to report concerns promptly. Those prescribed B12 replacement require follow-up to assess treatment response and determine ongoing requirements. Healthcare professionals should maintain awareness that GLP-1/GIP medicines, whilst highly effective for their intended indications, require holistic management addressing not only glycaemic control and weight but also nutritional status and overall metabolic health. Collaborative care involving GPs, diabetes specialist nurses, and dietitians optimises outcomes and minimises potential complications.

Patients are encouraged to report any suspected adverse reactions to medicines via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

Frequently Asked Questions