Berberine, a plant-derived alkaloid traditionally used in Chinese and Ayurvedic medicine, has attracted growing interest for its potential role in managing insulin resistance and improving glycaemic control. Insulin resistance—a condition in which the body's cells respond poorly to insulin—is a key driver of type 2 diabetes, prediabetes and metabolic syndrome. Whilst preliminary research suggests berberine may activate cellular pathways that enhance glucose uptake and reduce hepatic glucose production, it is not a licensed medicine in the UK and is not recommended by NICE. This article examines the mechanisms, clinical evidence, dosing considerations and safety profile of berberine in the context of insulin resistance.

What Is Insulin Resistance and How Does It Develop?

Insulin resistance is a metabolic condition in which the body's cells become less responsive to the hormone insulin, which is produced by the pancreas to regulate blood glucose levels. Under normal circumstances, insulin facilitates the uptake of glucose from the bloodstream into muscle, fat and liver cells, where it is used for energy or stored for later use. When cells fail to respond adequately to insulin, the pancreas compensates by producing more insulin, leading to elevated insulin levels (hyperinsulinaemia) and, eventually, raised blood glucose concentrations.

The development of insulin resistance is multifactorial and typically involves a combination of genetic predisposition, lifestyle factors and metabolic disturbances. Key contributors include:

• Obesity, particularly visceral (abdominal) adiposity, which promotes chronic low-grade inflammation and the release of free fatty acids that interfere with insulin signalling

• Physical inactivity, which reduces glucose uptake by skeletal muscle

• Dietary patterns high in refined carbohydrates and saturated fats

• Chronic inflammation and oxidative stress at the cellular level

• Hormonal imbalances, such as those seen in polycystic ovary syndrome (PCOS)

Over time, insulin resistance can progress to non-diabetic hyperglycaemia (also called prediabetes, defined as HbA1c 42–47 mmol/mol [6.0–6.4%] or fasting plasma glucose 5.5–6.9 mmol/L) and ultimately to type 2 diabetes mellitus (HbA1c ≥48 mmol/mol [6.5%] or fasting plasma glucose ≥7.0 mmol/L) if beta-cell function declines and the pancreas can no longer maintain adequate insulin secretion. Insulin resistance is also a core feature of metabolic syndrome, a cluster of conditions including hypertension, dyslipidaemia and central obesity that collectively increase cardiovascular risk.

Early identification and intervention—through lifestyle modification and, where appropriate, pharmacological support—are essential to prevent or delay these complications. People at high risk may be eligible for referral to the NHS Diabetes Prevention Programme. Symptoms of severe hyperglycaemia (excessive thirst, frequent urination, unexplained weight loss) or signs of dehydration or confusion warrant urgent medical assessment.

How Berberine Works to Improve Insulin Sensitivity

Berberine is a naturally occurring isoquinoline alkaloid extracted from various plants, including Berberis species (barberry), Coptis chinensis (goldthread) and Hydrastis canadensis (goldenseal). It has been used in traditional Chinese and Ayurvedic medicine for centuries, primarily for gastrointestinal infections, but contemporary research has revealed potential metabolic effects, particularly in relation to glucose homeostasis and insulin sensitivity.

The primary mechanism by which berberine may improve insulin sensitivity, based largely on laboratory and animal studies, is through activation of AMP-activated protein kinase (AMPK), a key cellular energy sensor. AMPK activation promotes glucose uptake in skeletal muscle and adipose tissue independently of insulin, enhances fatty acid oxidation, and inhibits hepatic gluconeogenesis (glucose production by the liver). This metabolic pathway shares some similarities with metformin, the first-line pharmacological agent for type 2 diabetes, though berberine and metformin have distinct molecular targets and berberine is not licensed as a medicine in the UK.

Additional mechanisms suggested by preclinical research include:

• Modulation of gut microbiota: Berberine may alter the composition of intestinal bacteria, which could influence metabolic endotoxin levels and systemic inflammation

• Reduction of oxidative stress and inflammation: Berberine exhibits antioxidant properties and may downregulate pro-inflammatory cytokines

• Improvement in lipid metabolism: It may reduce circulating triglycerides and low-density lipoprotein (LDL) cholesterol, which are often elevated in insulin-resistant states

• Potential enhancement of insulin receptor expression and signalling: Some laboratory studies suggest berberine might affect insulin receptor substrate-1 (IRS-1) and related pathways

While these mechanisms are biologically plausible, it's important to note that many have been primarily demonstrated in laboratory settings, and human mechanistic data remain limited. Berberine is available in the UK primarily as a food supplement, not as a licensed medicine.

Clinical Evidence for Berberine in Insulin Resistance

A growing body of clinical evidence suggests potential benefits of berberine in markers of insulin resistance and glycaemic control, though most studies have been conducted in Asian populations and the quality of evidence varies considerably.

Randomised controlled trials (RCTs) have investigated berberine, typically administered at doses of 900–1500 mg daily (divided into two or three doses), in individuals with type 2 diabetes or non-diabetic hyperglycaemia. Some small RCTs and meta-analyses suggest improvements in fasting blood glucose, haemoglobin A1c (HbA1c), and fasting insulin levels, but study quality is variable and findings should be interpreted cautiously. While some meta-analyses have suggested effects on glycaemic markers that appear comparable to metformin in short-term studies, these trials are generally small, of short duration, and heterogeneous in design, with potential publication bias.

In patients with polycystic ovary syndrome (PCOS), a condition characterised by insulin resistance and hyperandrogenism, preliminary studies suggest berberine might improve insulin sensitivity, reduce body mass index (BMI), and help restore menstrual regularity. However, evidence is preliminary and high-quality trials are needed before routine use could be considered.

Limitations of the current evidence include:

• Heterogeneity in study design, dosing regimens and participant characteristics

• Short duration of most trials (typically 8–16 weeks)

• Limited data from UK or European populations

• Lack of long-term safety and cardiovascular outcome data

It is important to note that berberine is not recommended by NICE for type 2 diabetes, non-diabetic hyperglycaemia or PCOS. NICE guidance emphasises structured education programmes, dietary modification, physical activity and, where indicated, pharmacotherapy with licensed agents such as metformin. Berberine should not be viewed as a substitute for these evidence-based approaches. Patients considering berberine should discuss this with their GP or diabetes specialist to ensure safe and appropriate use.

Dosage, Safety and Potential Side Effects of Berberine

Typical dosing regimens for berberine in clinical studies range from 900 to 1500 mg per day, usually divided into two or three doses taken with meals. This divided dosing strategy is employed because berberine has a relatively short half-life (approximately 4–6 hours) and poor oral bioavailability, meaning that frequent administration helps maintain therapeutic plasma concentrations. As berberine is not a licensed medicine in the UK, there is no official prescribing guidance, and products are sold as food supplements with variable quality and potency.

Gastrointestinal side effects are the most commonly reported adverse events and include:

• Diarrhoea

• Constipation

• Abdominal cramping or discomfort

• Nausea

These effects are generally mild to moderate and often resolve with continued use or dose reduction. Taking berberine with food may help minimise gastrointestinal upset.

Drug interactions are an important consideration. Berberine inhibits several cytochrome P450 enzymes (particularly CYP3A4 and CYP2D6) and P-glycoprotein (P-gp), and may alter the metabolism of co-administered medications, including:

• Anticoagulants (e.g., warfarin) and direct oral anticoagulants (e.g., apixaban, rivaroxaban, dabigatran)

• Antiplatelet agents

• Antihypertensives

• Statins (particularly those metabolised via CYP3A4)

• Immunosuppressants (e.g., ciclosporin, tacrolimus)

• Digoxin and certain antiarrhythmics

Patients taking these or other medications should consult their GP or pharmacist before starting berberine.

Contraindications and cautions include pregnancy and breastfeeding (due to insufficient safety data), use in children and adolescents, severe hepatic or renal impairment, and hypoglycaemia risk in individuals taking insulin or sulphonylureas. Serious adverse reactions appear uncommon in short trials, but long-term safety and post-marketing data for supplements are limited.

Patient advice: Individuals interested in berberine should seek guidance from a healthcare professional, particularly if they have existing medical conditions or are taking prescribed medications. Choose reputable UK suppliers, as supplement quality and potency can vary considerably. Consider stopping berberine 1-2 weeks before planned surgery. People taking glucose-lowering medications should monitor blood glucose levels and discuss potential dose adjustments with their healthcare provider. Berberine should be viewed as a complementary approach alongside evidence-based lifestyle interventions, not as a replacement for conventional treatment. If symptoms such as persistent gastrointestinal disturbance, unexplained fatigue, or signs of hypoglycaemia (sweating, tremor, confusion) occur, patients should contact their GP promptly. Suspected adverse reactions can be reported via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

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