Weight loss injections, particularly GLP-1 receptor agonists such as semaglutide (Wegovy) and liraglutide (Saxenda), have transformed obesity management in the UK. However, some patients find their expected results fail to materialise, raising the question: why are my weight loss injections not working? Several factors may explain suboptimal responses, including insufficient treatment duration, inadequate dose escalation, lifestyle factors, concurrent medications, and underlying medical conditions. These medications are MHRA-approved adjuncts to dietary modification and increased physical activity, prescribed within specialist NHS weight management services according to NICE criteria. Understanding the variables that influence treatment response helps identify areas for adjustment and sets realistic expectations for sustainable weight management outcomes.

Common Reasons Weight Loss Injections May Not Be Working

Weight loss injections, primarily glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide (Wegovy) and liraglutide (Saxenda), have become increasingly prescribed for weight management in the UK. These medications work by mimicking natural hormones that regulate appetite and blood glucose levels, slowing gastric emptying and promoting satiety. However, some patients find that their expected weight loss plateaus or fails to materialise, which can be frustrating and concerning.

Several factors may explain suboptimal responses to weight loss injections:

• Insufficient treatment duration – Meaningful weight loss typically requires several months of consistent treatment, with clinical trials showing progressive weight reduction over 12–16 weeks or longer. On average, patients may expect 10-15% weight loss with semaglutide and 5-10% with liraglutide after one year of treatment

• Unrealistic expectations – Whilst these medications are effective, individual responses vary considerably; not everyone will achieve the dramatic results sometimes portrayed in media coverage

• Inadequate dose escalation – Many weight loss injections require gradual dose increases to reach therapeutic levels whilst minimising side effects

• Lifestyle factors – These medications are designed to complement, not replace, dietary modifications and physical activity

It is important to understand that weight loss injections are not a standalone solution. In the UK, these medications are prescribed within specialist weight management services (tier 3) according to specific NICE criteria, including BMI thresholds and presence of weight-related conditions. They are approved by the MHRA as adjuncts to a reduced-calorie diet and increased physical activity.

Clinical trials demonstrating their efficacy included structured lifestyle interventions alongside pharmacotherapy. Additionally, individual metabolic differences and underlying health conditions can significantly influence treatment response. Some patients may experience initial weight loss followed by a plateau, which is a normal physiological adaptation rather than treatment failure. Understanding these variables helps set realistic expectations and identifies areas where adjustments might improve outcomes.

Medication Dosage and Titration Issues

Proper dosing and titration are critical to the effectiveness of weight loss injections. GLP-1 receptor agonists require careful dose escalation to balance therapeutic efficacy with tolerability. Starting at too low a dose or failing to progress to maintenance levels can significantly limit weight loss outcomes. Conversely, advancing too quickly may cause intolerable gastrointestinal side effects, leading to treatment discontinuation.

The typical titration schedule for semaglutide (Wegovy), for example, involves:

• Starting dose: 0.25 mg once weekly for 4 weeks

• Gradual increases: 0.5 mg, then 1 mg, then 1.7 mg at monthly intervals

• Maintenance dose: 2.4 mg once weekly

This graduated approach allows the body to adapt to the medication's effects whilst minimising nausea, vomiting, and other gastrointestinal symptoms. Some patients remain on sub-therapeutic doses due to side effects or prescriber caution, which may explain inadequate weight loss. If you have not progressed beyond the initial titration phases, you may not yet be receiving the full therapeutic benefit of the medication.

If you miss a dose and it's within 5 days of your scheduled injection, take it as soon as possible. If more than 5 days have passed, skip that dose and take your next injection on the regularly scheduled day. If side effects prevent dose escalation, your clinician may recommend pausing at your current dose until symptoms improve before attempting the next increase.

Timing and administration technique also matter. These injections should be administered consistently on the same day each week. For proper subcutaneous injection technique, use the abdomen, thigh, or upper arm, rotating injection sites with each dose. Avoid injecting into areas that are bruised, scarred, tender or have lipodystrophy (abnormal fat tissue).

If you suspect dosing issues, do not adjust your medication independently. Never exceed the licensed maximum dose. Your prescriber can review your current regimen, assess your tolerance to dose increases, and determine whether advancing to a higher maintenance dose is appropriate. Some individuals require longer titration periods or may benefit from alternative GLP-1 receptor agonists if one particular formulation proves ineffective, but this should only be considered under medical supervision.

Lifestyle Factors That Affect Weight Loss Injection Effectiveness

Weight loss injections are pharmacological tools designed to work synergistically with lifestyle modifications, not as replacements for healthy behaviours. The most common reason for suboptimal results is insufficient attention to dietary intake and physical activity. Even with appetite suppression from GLP-1 receptor agonists, consuming calorie-dense foods or maintaining sedentary habits can prevent meaningful weight loss.

Key lifestyle factors that influence treatment outcomes include:

• Dietary composition and quality – Whilst these medications reduce appetite, choosing nutrient-dense, lower-calorie foods maximises weight loss. Consuming ultra-processed foods, excessive alcohol, or high-sugar beverages can counteract the medication's effects

• Portion control – Some patients eat less frequently but consume large portions when they do eat, negating the caloric deficit needed for weight loss

• Physical activity levels – UK Chief Medical Officers' guidelines recommend at least 150 minutes of moderate-intensity or 75 minutes of vigorous activity weekly, plus muscle-strengthening activities on at least 2 days per week. Exercise preserves lean muscle mass during weight loss and improves metabolic health

• Sleep quality and duration – Poor sleep disrupts hormones that regulate hunger and metabolism, potentially diminishing treatment response

• Stress and emotional eating – Chronic stress elevates cortisol levels, which can promote fat retention and trigger eating behaviours that override medication-induced satiety

Alcohol consumption deserves particular mention, as it provides empty calories (7 kcal per gram) and can stimulate appetite whilst impairing judgement around food choices. Additionally, some patients compensate for reduced appetite by consuming more calorie-dense foods during eating occasions, inadvertently maintaining their previous caloric intake.

Keeping a food diary or using a nutrition tracking application can reveal patterns that may be limiting your progress. Many patients benefit from referral to a registered dietitian who can provide personalised guidance compatible with GLP-1 therapy. Similarly, working with a physiotherapist, qualified exercise professional, or joining an NHS exercise referral scheme can help establish sustainable habits that complement pharmacotherapy.

Medical Conditions and Medications That May Interfere

Several underlying medical conditions and concurrent medications can impair the effectiveness of weight loss injections or make weight loss more challenging despite treatment. Understanding these potential interactions is essential for optimising outcomes and identifying when additional medical evaluation may be warranted.

Endocrine disorders frequently affect weight regulation. Hypothyroidism slows metabolic rate and can cause weight gain or prevent weight loss even with appropriate treatment. Polycystic ovary syndrome (PCOS) involves insulin resistance and hormonal imbalances that complicate weight management. Cushing's syndrome, though rare, causes weight gain through excess cortisol production. If you have been diagnosed with any endocrine condition, ensuring optimal management of that condition is crucial for weight loss success.

Medications that may promote weight gain or interfere with weight loss include:

• Antipsychotics – Particularly olanzapine and clozapine, which significantly affect metabolism and appetite

• Antidepressants – Particularly mirtazapine and some tricyclic antidepressants; SSRIs have variable effects

• Corticosteroids – Prednisolone and other glucocorticoids increase appetite and promote fat deposition

• Diabetes medications – Insulin, sulphonylureas, and thiazolidinediones can cause weight gain

• Beta-blockers – Some formulations may slow metabolism slightly

• Anticonvulsants – Valproate and certain other seizure medications affect weight

Do not stop or change any prescribed medications without consulting your healthcare provider, even if you suspect they may be affecting your weight loss.

Conditions that may affect GLP-1 treatment safety or efficacy include:

• History of pancreatitis

• Gallbladder disease

• Severe gastrointestinal disorders, including gastroparesis

• Kidney problems, especially if dehydration occurs from side effects

Insulin resistance and metabolic syndrome can also diminish response to weight loss interventions. For patients with type 2 diabetes or PCOS, metformin may be prescribed alongside GLP-1 therapy where clinically indicated, but this should only be under medical supervision.

GLP-1 medications are not recommended during pregnancy or breastfeeding. If you are of childbearing potential, effective contraception is advised during treatment, and you should follow the recommended washout period before trying to conceive.

Genetic factors influence individual responses to weight loss medications, though routine genetic testing is not currently standard practice in the NHS. If you have a strong family history of obesity or have found multiple weight loss approaches ineffective, discussing this with your healthcare provider may help identify whether additional investigations or specialist referral would be beneficial.

When to Speak to Your Healthcare Provider

Knowing when to seek medical advice about your weight loss injection treatment is important for both safety and optimising outcomes. Whilst some degree of individual variation in response is normal, certain situations warrant professional review and potential treatment adjustment.

You should contact your GP or prescribing clinician if:

• No weight loss after 12–16 weeks at the maintenance dose – Clinical trials typically show measurable weight reduction within this timeframe; lack of response may indicate the need for dose adjustment, medication change, or further investigation

• Significant side effects preventing dose escalation – Persistent nausea, vomiting, or other adverse effects that limit your ability to reach therapeutic doses require medical assessment

• Weight regain after initial loss – This may suggest tolerance development, inadequate dosing, or underlying medical issues requiring attention

• Symptoms suggesting complications – Severe abdominal pain, persistent vomiting, visual changes, or signs of pancreatitis (severe upper abdominal pain radiating to the back) require urgent medical evaluation

• Concerns about injection technique or medication storage – Improper administration or storage can reduce effectiveness

Seek urgent same-day medical care (via NHS 111, 999 or A&E as appropriate) and stop your medication if you experience:

• Severe, persistent upper abdominal pain which may radiate to your back (possible pancreatitis)

• Severe right-sided upper abdominal pain, fever, or yellowing of the skin/eyes (possible gallbladder problems)

• Severe, persistent vomiting leading to dehydration

Your healthcare provider can conduct a comprehensive review including medication adherence, injection technique, lifestyle factors, and potential medical barriers to weight loss. They may recommend blood tests to assess thyroid function, glucose metabolism, or other relevant parameters. In some cases, referral to specialist weight management services may be appropriate, particularly if you have complex medical needs or have not responded to first-line interventions.

In the UK, GLP-1 treatments are prescribed within specialist weight management services with regular monitoring. For semaglutide (Wegovy), NICE guidance currently limits treatment duration to up to 2 years. Your prescriber should be reviewing your progress at appropriate intervals, typically every 4–12 weeks initially, then less frequently once stable.

Do not discontinue your medication without medical advice, as weight regain is common after stopping treatment. Similarly, never increase your dose independently or obtain medications from unregulated sources, as this poses significant safety risks. Open communication with your healthcare team is essential for achieving the best possible outcomes from weight loss injection therapy.

If you experience any suspected side effects, report them to the MHRA Yellow Card scheme, which helps monitor the safety of medications.

Frequently Asked Questions