Wegovy (semaglutide 2.4 mg) is a once-weekly injectable medication licensed in the UK for weight management in adults with obesity or overweight with weight-related conditions. Whilst Wegovy for insulin resistance is not a specific licensed indication, the substantial weight loss achieved—typically 10-15% of body weight—can significantly improve insulin sensitivity and glycaemic control. Insulin resistance, where cells become less responsive to insulin, is a key driver of type 2 diabetes and metabolic syndrome. This article examines how Wegovy works, who may benefit, expected metabolic improvements, and important safety considerations for UK patients considering this treatment under specialist supervision.

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. When cells in muscle, fat, and liver tissue fail to respond adequately to insulin, the pancreas compensates by producing more insulin to maintain normal blood glucose. Over time, this compensatory mechanism can become insufficient, leading to elevated blood glucose levels and potentially progressing to type 2 diabetes mellitus.

The development of insulin resistance is multifactorial and closely linked to excess adiposity, particularly visceral fat accumulation around abdominal organs. Adipose tissue, especially when excessive, releases inflammatory cytokines and free fatty acids that interfere with insulin signalling pathways at the cellular level. Genetic predisposition plays a role, but modifiable lifestyle factors are significant contributors. Physical inactivity reduces glucose uptake by skeletal muscle, whilst diets high in refined carbohydrates and saturated fats promote metabolic dysfunction.

Insulin resistance rarely presents with obvious symptoms in its early stages, making it a silent contributor to cardiovascular disease, non-alcoholic fatty liver disease, and polycystic ovary syndrome. Clinical detection typically occurs through blood tests showing elevated fasting glucose, impaired glucose tolerance, or raised HbA1c levels. In the UK, prediabetes (non-diabetic hyperglycaemia) is defined as HbA1c 42-47 mmol/mol or fasting plasma glucose 5.5-6.9 mmol/L. Type 2 diabetes is diagnosed when HbA1c ≥48 mmol/mol, fasting plasma glucose ≥7.0 mmol/L, or 2-hour oral glucose tolerance test ≥11.1 mmol/L. The homeostatic model assessment of insulin resistance (HOMA-IR) can quantify the degree of insulin resistance, though this is primarily a research tool not recommended for routine diagnosis in UK primary care.

According to Diabetes UK and Public Health England data, insulin resistance affects a significant proportion of adults with obesity in the UK and is a key driver of the type 2 diabetes epidemic. Early identification and intervention through lifestyle modification remain the cornerstone of management, though pharmacological options are increasingly considered for those at high metabolic risk.

How Wegovy Works in the Body

Wegovy is the brand name for semaglutide 2.4 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist licensed by the MHRA for weight management in adults with obesity or overweight with weight-related comorbidities. It is important to note that Wegovy is not specifically licensed for treating insulin resistance itself. Semaglutide is a synthetic analogue of human GLP-1, a naturally occurring incretin hormone released from intestinal L-cells in response to food intake. The medication has a prolonged half-life of approximately one week, allowing for once-weekly subcutaneous administration.

The primary mechanism of action involves binding to GLP-1 receptors in multiple tissues, including the pancreas, brain, and gastrointestinal tract. In pancreatic beta cells, semaglutide enhances glucose-dependent insulin secretion, meaning insulin release is stimulated only when blood glucose levels are elevated, thereby reducing the risk of hypoglycaemia. Simultaneously, it suppresses glucagon secretion from pancreatic alpha cells, which helps prevent excessive hepatic glucose production.

Wegovy exerts significant effects on appetite regulation through actions in the hypothalamus and brainstem, reducing hunger and increasing satiety. This leads to decreased caloric intake, which is the principal driver of weight loss. Gastric emptying is also slowed, contributing to prolonged feelings of fullness after meals. The resulting weight reduction, particularly loss of visceral adipose tissue, directly improves insulin sensitivity by reducing inflammatory mediators and free fatty acid flux. Additionally, GLP-1 receptor agonists like semaglutide have some weight-independent effects on glucose metabolism.

Whilst Wegovy is not specifically licensed for treating insulin resistance, the metabolic improvements associated with substantial weight loss—typically 10-15% of body weight in clinical trials—translate into measurable enhancements in insulin sensitivity, glycaemic control, and cardiovascular risk markers. The STEP clinical trial programme has demonstrated reductions in HbA1c, fasting glucose, and insulin resistance markers in individuals with prediabetes and metabolic syndrome, with benefits correlating strongly with the degree of weight loss achieved.

Who Can Use Wegovy for Metabolic Health in the UK

In the UK, Wegovy is licensed for adults with a body mass index (BMI) of 30 kg/m² or greater, or a BMI of 27 kg/m² or greater in the presence of at least one weight-related comorbidity such as hypertension, dyslipidaemia, obstructive sleep apnoea, or cardiovascular disease. It's important to note that for people of South Asian, Chinese, other Asian, Middle Eastern, Black African, or African-Caribbean ethnicity, lower BMI thresholds may be appropriate when assessing health risks, as per NICE obesity guidance.

However, NHS access to Wegovy is more restricted than the licence. NICE Technology Appraisal 875 (TA875) specifies that NHS-funded treatment is available only through specialist weight management services for adults with a BMI of at least 35 kg/m² (or 32.5 kg/m² for certain ethnic groups) and at least one weight-related comorbidity. NHS treatment is limited to a maximum of 2 years.

For individuals with insulin resistance who do not yet have a diagnosis of type 2 diabetes, Wegovy may be appropriate if they meet the BMI criteria and have evidence of metabolic dysfunction. This might include prediabetes (HbA1c 42-47 mmol/mol), metabolic syndrome, or polycystic ovary syndrome with associated weight gain. The decision to prescribe should be made by a specialist weight management service or an appropriately trained clinician following comprehensive metabolic assessment.

Certain populations require careful consideration. The medication should not be used during pregnancy or breastfeeding, and women of childbearing potential should use effective contraception. Women planning pregnancy should discontinue Wegovy at least 2 months before conception. The UK SmPC notes that rodent studies showed an increased risk of thyroid C-cell tumours with semaglutide, though the human relevance is unknown. Patients should report any thyroid symptoms such as neck lumps or persistent hoarseness. Wegovy should not be used concurrently with other GLP-1 receptor agonists or weight management medications.

NHS England has implemented a phased rollout of Wegovy through specialist weight management services, with prioritisation based on clinical need and resource availability. Access remains limited compared to demand, and many patients may face waiting times. Private prescription is an alternative, though cost considerations are substantial. All patients must demonstrate commitment to dietary modification and increased physical activity as part of a comprehensive weight management programme for treatment to be initiated and continued.

Expected Results and Treatment Duration

Clinical trial data from the STEP (Semaglutide Treatment Effect in People with obesity) programme demonstrates that adults using Wegovy alongside lifestyle intervention achieve an average weight loss of 12-15% of initial body weight over 68 weeks, compared to approximately 2-3% with placebo. Individual responses vary considerably, with some patients losing more than 20% of body weight whilst others experience more modest reductions. Weight loss typically begins within the first month and continues progressively during the dose escalation phase.

Improvements in insulin sensitivity and glycaemic parameters generally parallel weight reduction. The STEP trials show that individuals with prediabetes using semaglutide experience significant reductions in fasting glucose and HbA1c, with many reverting to normoglycaemia. Insulin resistance markers typically improve substantially in those achieving significant weight loss. These metabolic benefits emerge within 12-16 weeks but continue to improve as weight loss progresses.

When prescribed through NHS specialist weight management services, NICE TA875 specifies a maximum treatment duration of 2 years. Continuation of treatment should be regularly reviewed according to local specialist service protocols, which may include assessment of weight loss achieved and metabolic improvements. Private prescribing is not bound by the 2-year NHS limitation, though regular clinical review remains essential.

The STEP 4 trial and extension studies demonstrate that benefits are maintained whilst treatment continues, but weight regain commonly occurs after discontinuation, with corresponding deterioration in metabolic parameters. Some patients may require long-term treatment, similar to management of other chronic conditions, though this must be balanced against cost, side effects, and individual circumstances.

Regular monitoring throughout treatment should include weight, blood pressure, glycaemic parameters (HbA1c, fasting glucose), lipid profile, and renal function. For patients with type 2 diabetes, retinopathy screening is important due to potential risk of worsening retinopathy with rapid improvements in glycaemic control. The frequency of monitoring should follow local protocols, with reassessment of the risk-benefit balance at regular intervals by the prescribing clinician.

Side Effects and Safety Considerations

Gastrointestinal adverse effects are the most commonly reported side effects with Wegovy, affecting the majority of users to some degree. Nausea is particularly prevalent, especially during dose escalation, occurring in approximately 40-50% of patients in clinical trials. Vomiting, diarrhoea, constipation, and abdominal discomfort are also frequent. These symptoms are generally mild to moderate in severity and tend to diminish over time as tolerance develops. The gradual dose titration schedule—starting at 0.25 mg weekly and increasing monthly to the target 2.4 mg dose—is specifically designed to minimise gastrointestinal intolerance. If the 2.4 mg dose is not tolerated, the SmPC permits maintenance at 1.7 mg as an alternative.

Patients should be advised to eat smaller, more frequent meals, avoid high-fat foods, and stay well hydrated to manage gastrointestinal symptoms. If nausea or vomiting becomes severe or persistent, delaying dose escalation or temporarily reducing the dose may be necessary. Severe gastrointestinal symptoms warrant medical review, as dehydration and electrolyte disturbances can occur, potentially leading to acute kidney injury, particularly in vulnerable individuals.

More serious but less common adverse effects require clinical vigilance. Acute pancreatitis has been reported with GLP-1 receptor agonists, though causality remains uncertain. Patients should be counselled to seek immediate medical attention if they develop severe, persistent abdominal pain radiating to the back, especially if accompanied by vomiting. Gallbladder disease, including cholelithiasis and cholecystitis, occurs more frequently with rapid weight loss and has been observed in clinical trials. The UK SmPC notes that rodent studies showed an increased risk of thyroid C-cell tumours, though the human relevance is unknown. Patients should report any thyroid symptoms such as neck lumps or persistent hoarseness.

Additional safety considerations include small increases in heart rate and potential worsening of diabetic retinopathy in people with type 2 diabetes, particularly with rapid improvement in glycaemic control. Hypoglycaemia is uncommon with Wegovy monotherapy due to its glucose-dependent mechanism, but risk increases if used alongside sulfonylureas or insulin in patients with diabetes.

Injection site reactions are usually mild. Patients should be educated on proper subcutaneous injection technique, rotating injection sites between abdomen, thigh, and upper arm. Clear 'sick day rules' should be provided, advising when to seek medical help for persistent vomiting or signs of dehydration. Regular follow-up with healthcare professionals is essential to monitor efficacy, tolerability, and any emerging safety concerns.

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