Metformin for treatment of obesity is an area of growing interest, though the drug is not licensed for this indication in the UK. Metformin is a biguanide medication approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for managing type 2 diabetes mellitus, where it improves insulin sensitivity and reduces hepatic glucose production. Whilst metformin is not a dedicated anti-obesity medication, clinical evidence shows it may produce modest weight reductions when used alongside lifestyle interventions. This article examines the evidence base, appropriate patient selection, expected outcomes, safety considerations, and alternative approaches to obesity management within the UK healthcare context.

What Is Metformin and How Does It Work for Weight Management?

Metformin is a biguanide medication licensed in the UK for the treatment of type 2 diabetes mellitus. According to the UK Summary of Product Characteristics (SmPC) and British National Formulary (BNF), it works by reducing hepatic glucose production, decreasing intestinal glucose absorption, and improving insulin sensitivity in peripheral tissues. The Medicines and Healthcare products Regulatory Agency (MHRA) has approved metformin for glycaemic control, not specifically for obesity treatment, though weight effects have been observed in clinical practice.

The mechanisms by which metformin may influence body weight are multifactorial and not fully understood. Research suggests the drug activates AMP-activated protein kinase (AMPK), a cellular energy sensor that regulates metabolic processes. Early evidence indicates this activation may reduce appetite through effects on hypothalamic pathways and alter gut hormone secretion, including glucagon-like peptide-1 (GLP-1). Additionally, metformin appears to modify gut microbiome composition, which may contribute to metabolic effects. However, these mechanisms remain under investigation and are not established as the primary determinants of clinical weight loss.

Weight changes associated with metformin are typically modest and occur as a secondary effect rather than through a primary anti-obesity mechanism. Unlike diabetes medications that can cause weight gain (such as sulphonylureas or insulin), metformin tends to be weight-neutral or associated with small reductions in body weight. This characteristic makes it an attractive option for patients with type 2 diabetes who are overweight or obese.

Metformin is available in immediate-release (IR) and modified-release (MR) formulations. The typical licensed maximum dose is 2000 mg daily (IR) or 2000 mg daily (MR), though some patients may require up to 3000 mg daily in divided doses under specialist guidance. It is important to emphasise that metformin is not licensed as a weight loss medication in the UK. Any use for obesity management alone would constitute off-label prescribing, which requires careful clinical justification and informed patient consent. The drug should always be considered as part of a comprehensive approach including dietary modification and increased physical activity.

Clinical Evidence for Metformin in Obesity Treatment

The evidence base for metformin in obesity management comes primarily from studies in patients with type 2 diabetes, non-diabetic hyperglycaemia (NDH), or polycystic ovary syndrome (PCOS), rather than obesity as an isolated indication. The landmark Diabetes Prevention Programme (DPP), published in the New England Journal of Medicine in 2002, demonstrated that metformin reduced the incidence of type 2 diabetes in high-risk individuals and was associated with modest weight loss of approximately 2–3 kg over one year, though this was significantly less effective than intensive lifestyle intervention. Long-term follow-up in the Diabetes Prevention Programme Outcomes Study (DPPOS) confirmed sustained but modest effects.

A systematic review and meta-analysis published in Obesity Reviews examined metformin use in non-diabetic obese individuals and found mean weight reductions of approximately 2.9 kg compared to placebo over 6–12 months. However, the quality of evidence was variable, with significant heterogeneity between studies, and the weight loss observed was generally modest and not sustained in all participants.

In patients with PCOS, metformin has shown benefits for both metabolic parameters and modest weight reduction, particularly when combined with lifestyle interventions. The Royal College of Obstetricians and Gynaecologists (RCOG) and NICE Clinical Knowledge Summaries (CKS) on PCOS acknowledge metformin's role in improving insulin sensitivity, though evidence for weight loss is limited and inconsistent.

Current UK guidelines do not recommend metformin specifically for obesity treatment. NICE guideline CG189 on obesity management focuses on lifestyle interventions, psychological support, and pharmacological options such as orlistat, or GLP-1 receptor agonists (liraglutide 3.0 mg [NICE TA664], semaglutide 2.4 mg [NICE TA875]) which have stronger evidence for weight reduction. NICE Public Health guideline PH38 does recommend considering metformin for diabetes prevention in adults at high risk of non-diabetic hyperglycaemia when intensive lifestyle interventions have not been effective, but this is distinct from obesity treatment per se. The Royal College of Physicians emphasises that any pharmacological intervention should be adjunctive to, not a replacement for, comprehensive lifestyle modification. There is no official indication for metformin monotherapy in obesity without concurrent diabetes or non-diabetic hyperglycaemia.

Who May Be Prescribed Metformin for Weight Loss in the UK?

Within NHS practice, metformin is most appropriately prescribed for individuals who have both obesity and either type 2 diabetes or non-diabetic hyperglycaemia (impaired glucose tolerance or impaired fasting glucose). In these populations, metformin addresses the underlying metabolic dysfunction whilst potentially offering modest weight benefits. NICE guideline NG28 recommends offering metformin as first-line pharmacological treatment for most adults with type 2 diabetes, unless contraindicated or not tolerated, irrespective of body mass index (BMI).

Patients with polycystic ovary syndrome (PCOS) and obesity may also be offered metformin, particularly when insulin resistance is present. The Royal College of Obstetricians and Gynaecologists and NICE CKS recognise metformin's role in improving metabolic and reproductive outcomes in PCOS, though its use should be discussed as part of holistic management including lifestyle interventions.

Off-label prescribing of metformin for obesity alone (without diabetes, non-diabetic hyperglycaemia, or PCOS) is not supported by current UK guidelines and would require exceptional clinical justification. Such prescribing decisions should involve:

• Thorough discussion of the limited evidence base for weight loss

• Clear documentation of why licensed alternatives are unsuitable

• Informed patient consent acknowledging off-label use

• Regular monitoring and review of treatment efficacy

Metformin is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) and should not be initiated in patients with eGFR 30–44 mL/min/1.73m² without specialist advice. It is also contraindicated in acute metabolic acidosis, severe hepatic impairment, or conditions predisposing to tissue hypoxia (such as decompensated heart failure, acute myocardial infarction, or severe respiratory disease). Metformin should be stopped at or before procedures involving iodinated contrast media or major surgery, and restarted at least 48 hours afterwards once renal function is confirmed to be stable. Caution is required in older adults and patients with excessive alcohol intake.

Before initiating metformin, baseline renal function (eGFR), liver function, and HbA1c (if relevant) should be assessed. Renal function should be monitored at least annually, or more frequently in patients with eGFR 45–59 mL/min/1.73m² or other risk factors. Prescribers should ensure patients understand that metformin is not a substitute for dietary changes and increased physical activity, which remain the cornerstone of obesity management. Metformin should not be used for weight loss during pregnancy. Metformin may be used for diabetes or gestational diabetes in pregnancy under specialist guidance, but weight loss is not an appropriate goal in pregnancy.

Expected Weight Loss Results and Timeframes with Metformin

Patients considering metformin should have realistic expectations regarding weight loss outcomes. Clinical trial data, including the Diabetes Prevention Programme and systematic reviews, consistently show that metformin produces modest weight reductions, typically in the range of 2–5 kg over 6–12 months when used in conjunction with lifestyle interventions. This represents approximately 2–5% of initial body weight for most individuals. By comparison, intensive lifestyle modification programmes can achieve 5–10% weight loss in motivated participants, though real-world outcomes vary. Newer anti-obesity medications produce greater weight loss: semaglutide 2.4 mg achieves approximately 12–15% weight reduction, whilst liraglutide 3.0 mg achieves approximately 5–8% weight reduction, as demonstrated in NICE technology appraisals TA875 and TA664 respectively.

The timeframe for observable weight changes varies between individuals. Some patients may notice gradual weight reduction within the first 3–6 months of treatment, whilst others experience minimal or no weight loss despite continued use. Weight loss with metformin tends to plateau after 6–12 months, and there is limited evidence for sustained progressive weight reduction beyond this period. Evidence regarding weight regain after metformin discontinuation is limited, though some studies suggest weight may return towards baseline, highlighting that any benefits are likely dependent on continued treatment.

Individual response to metformin is highly variable and influenced by multiple factors including baseline insulin resistance, adherence to lifestyle modifications, and possibly genetic polymorphisms affecting drug metabolism. Patients with higher degrees of insulin resistance or non-diabetic hyperglycaemia may experience greater weight loss than those with normal insulin sensitivity. Age, sex, and ethnicity may also influence treatment response, though evidence is inconsistent.

Clinicians should emphasise that metformin is not a standalone solution for obesity management. The medication should be positioned as a potential adjunct to comprehensive lifestyle interventions including caloric restriction, increased physical activity, behavioural therapy, and ongoing support. Regular monitoring (typically every 3–6 months) allows assessment of treatment efficacy. If no meaningful weight loss or metabolic improvement is observed after 6 months of optimal therapy combined with lifestyle changes, clinicians may wish to discuss alternative approaches with the patient, though there is no formal UK guideline-mandated stopping rule for off-label metformin use in obesity.

Side Effects and Safety Considerations

Gastrointestinal side effects are the most common adverse reactions to metformin, affecting up to 30% of patients. These include diarrhoea, nausea, abdominal discomfort, bloating, and metallic taste. Symptoms typically emerge within the first few weeks of treatment and often diminish with continued use. To minimise gastrointestinal intolerance, metformin should be initiated at a low dose (500 mg once or twice daily with meals) and titrated gradually over several weeks to the target dose (typically 1500–2000 mg daily in divided doses). Modified-release formulations may improve tolerability in some patients.

The most serious, though very rare, adverse effect is lactic acidosis, a potentially fatal condition. According to the MHRA and UK SmPC, risk factors include renal impairment, hepatic dysfunction, acute illness, conditions associated with tissue hypoxia (such as decompensated heart failure, acute myocardial infarction, or severe respiratory disease), excessive alcohol intake, and use of iodinated contrast media. Patients should be advised to:

• Report symptoms such as unusual muscle pain, breathing difficulties, severe fatigue, or abdominal pain immediately

• Avoid excessive alcohol consumption

• Inform healthcare providers about metformin use before procedures involving contrast media or surgery

• Seek immediate medical attention if they become acutely unwell

Metformin should be stopped at or before procedures involving iodinated contrast media or major surgery, and restarted at least 48 hours afterwards once renal function is confirmed to be stable.

Vitamin B12 deficiency occurs in approximately 10–30% of long-term metformin users due to impaired intestinal absorption. The MHRA Drug Safety Update (2022) advises that healthcare professionals should be aware of the risk, particularly in patients on higher doses or longer duration of treatment. Consider testing vitamin B12 levels if deficiency is suspected (symptoms include fatigue, glossitis, paraesthesia, or signs of anaemia or neuropathy), and consider periodic monitoring in patients at risk. Supplementation should be offered if deficiency is confirmed.

Hypoglycaemia is unlikely with metformin monotherapy but may occur when metformin is combined with insulin or sulphonylureas. Other considerations include potential drug interactions (particularly with cationic drugs eliminated by renal tubular secretion) and dose adjustment in moderate renal impairment. In patients with eGFR 45–59 mL/min/1.73m², review the dose and monitor renal function every 3–6 months. In patients with eGFR 30–44 mL/min/1.73m², the maximum dose is 1000 mg daily, and renal function should be monitored every 3 months.

Patients should be counselled to contact their GP if they experience persistent gastrointestinal symptoms, signs of lactic acidosis, or symptoms suggestive of vitamin B12 deficiency. Suspected adverse reactions should be reported via the MHRA Yellow Card Scheme at yellowcard.mhra.gov.uk or through the Yellow Card app.

Alternatives to Metformin for Obesity Management

Lifestyle interventions remain the foundation of obesity management in the UK. NICE guideline CG189 and Public Health guideline PH53 recommend multicomponent interventions including dietary modification (aiming for 600 kcal/day deficit), increased physical activity, and behavioural strategies. The UK Chief Medical Officers' Physical Activity Guidelines (2019) recommend at least 150 minutes of moderate-intensity activity per week for general health, with higher volumes (225–300 minutes weekly) often needed to support weight loss and maintenance. Structured programmes such as NHS-commissioned weight management services or evidence-based commercial programmes have demonstrated effectiveness for achieving clinically meaningful weight loss.

Pharmacological alternatives with stronger evidence for obesity treatment include:

• Orlistat (licensed for BMI ≥30 kg/m² or ≥28 kg/m² with comorbidities): A lipase inhibitor that reduces dietary fat absorption by approximately 30%, typically producing 2–3 kg additional weight loss compared to placebo over one year. Gastrointestinal side effects are common. According to NICE CKS and the SmPC, orlistat should be discontinued if less than 5% of initial body weight has been lost after 12 weeks of treatment. Orlistat is contraindicated in cholestasis and chronic malabsorption syndromes.

• GLP-1 receptor agonists: Liraglutide 3.0 mg (Saxenda) is recommended by NICE (TA664) for weight management in adults with BMI ≥35 kg/m² (or ≥32.5 kg/m² in certain ethnic groups) and at least one weight-related comorbidity, as an adjunct to diet and exercise. Semaglutide 2.4 mg (Wegovy) is recommended by NICE (TA875) under similar criteria. These agents produce substantially greater weight loss (liraglutide approximately 5–8%; semaglutide approximately 12–15% of initial body weight) than metformin. NHS availability is subject to local commissioning decisions and eligibility criteria, and supply constraints have affected access in some areas.

• Naltrexone/bupropion combination (Mysimba): Licensed for obesity management in the UK, though commissioning varies by local formulary and it is less commonly prescribed due to cost and side effect profile. Clinicians should check local guidance.

Bariatric surgery represents the most effective intervention for severe obesity. NICE guideline CG189 recommends considering surgical options including gastric bypass, sleeve gastrectomy, or adjustable gastric banding for adults with BMI ≥40 kg/m² (or ≥37.5 kg/m² for people of South Asian family origin), or BMI ≥35 kg/m² (or ≥32.5 kg/m² for people of South Asian family origin) with other significant obesity-related comorbidities. NICE guideline NG28 recommends considering bariatric surgery at an earlier stage (BMI ≥30 kg/m²) for adults with type 2 diabetes and recent diagnosis. Referral should be made to Tier 3 specialist weight management services, with onward referral to Tier 4 bariatric surgery services for eligible patients. Surgery typically produces 20–30% total body weight loss and significant improvement in obesity-related comorbidities.

Emerging therapies include dual GLP-1/GIP receptor agonists (tirzepatide) and other novel agents in development, though these are not yet widely available in the UK. For patients with specific conditions such as PCOS, addressing underlying hormonal imbalances through appropriate endocrine management may facilitate weight loss. Ultimately, the choice of intervention should be individualised based on patient characteristics, comorbidities, preferences, and local commissioning arrangements, with realistic discussions about expected outcomes and the need for long-term commitment to lifestyle changes regardless of pharmacological or surgical interventions chosen.

Frequently Asked Questions