When Weight Loss Medicines Stop Working – Why Plateaus Happen and What You Can Do Next

Jaydev Varsani – Clinical Pharmacist

Weight loss injections and tablets have transformed obesity treatment. For many patients, medicines such as GLP-1 and GLP-GIP based therapies help reduce appetite, improve portion control, and support meaningful weight loss.

However, not everyone responds in the same way.

Some patients lose weight steadily for several months and then hit a plateau. Others notice minimal response from the outset despite good adherence. This can be frustrating and demoralising, especially when you feel you are doing everything correctly.

The good news is that a plateau does not necessarily mean failure or that treatment has stopped working. It often signals that your body has adapted — and that it’s time to reassess the bigger clinical picture.

Let’s unpack why this happens and what can realistically be done next.

What Does a Weight Loss Plateau Mean?

A plateau is when weight loss slows significantly or stops altogether for several weeks, despite staying on treatment and maintaining similar eating patterns.

This happens because the body is highly efficient at defending its weight. As you lose weight:

• Your metabolism naturally slows.

• Hunger hormones begin to increase again.

• Energy expenditure reduces.

• The body becomes more resistant to further fat loss.

This biological adaptation is normal — not a personal failure.

In some cases, plateaus reveal underlying medical or lifestyle factors that limit how well the medication can work.

Why Some People Respond Less Well to Weight Loss Medicines

1. Individual Biology and Hormonal Differences

Not everyone’s appetite pathways respond equally to GLP-1 stimulation. Genetics, gut hormone sensitivity, insulin resistance, and metabolic health all influence response.

Some patients require longer titration, others plateau earlier, and a small group may not respond meaningfully despite appropriate dosing.

2. Insulin Resistance and Metabolic Health

If the body is significantly insulin resistant, weight loss can be slower and harder to sustain. Fat storage remains prioritised, and hunger signalling may stay elevated.

This is particularly relevant in patients with:

• Prediabetes or type 2 diabetes

• Central weight gain

• Polycystic ovary syndrome (PCOS)

• Strong family history of metabolic disease

Blood testing can help assess glucose control, insulin resistance, lipid health, liver markers and thyroid function — all of which influence weight response.

Medications That Can Interfere with Weight Loss

Many commonly prescribed medicines can blunt weight loss or promote weight gain, even when using weight loss injections.

Examples include:

• Steroids (e.g. prednisolone) – increase appetite and fat storage

• Certain antidepressants and antipsychotics – alter appetite and metabolism

• Insulin and sulfonylureas – promote weight gain in diabetes

• Beta-blockers – can reduce metabolic rate and exercise tolerance

• Hormonal therapies – may affect fluid balance and fat distribution

• Some epilepsy medicines – can impact appetite and metabolism

This does not mean these medicines should be stopped — but it highlights the importance of medication review when progress stalls. Sometimes small adjustments or expectations need recalibrating.

Smoking, Nicotine and Weight Loss

Nicotine affects appetite, cortisol levels, insulin sensitivity, sleep quality and gut hormones. While some people believe smoking suppresses appetite, the metabolic impact is often counterproductive for sustainable fat loss.

Smoking can:

• Increase insulin resistance

• Disrupt hunger and satiety signalling

• Elevate stress hormones

• Impair cardiovascular fitness and recovery

• Worsen inflammation and metabolic efficiency

Patients who smoke or vape often experience more unpredictable weight responses and plateaus. Addressing nicotine habits can significantly improve long-term metabolic health and weight stability.

Stress – The Silent Saboteur of Weight Loss

Chronic stress is one of the most underestimated causes of stalled weight loss.

When stress levels remain high:

• Cortisol increases fat storage, especially around the abdomen

• Hunger hormones become dysregulated

• Emotional eating becomes more likely

• Sleep quality drops, worsening appetite control

• Blood sugar regulation becomes less stable

Even with excellent medication adherence, persistent stress can block progress. In real-world practice, this is often the missing piece when patients plateau unexpectedly.

Weight loss is not just pharmacology — it is physiology, psychology and lifestyle combined.

When Blood Testing Can Add Value

If weight loss has plateaued or response has been limited, targeted blood testing can help identify reversible contributors, such as:

• Thyroid dysfunction

• Insulin resistance or early diabetes

• Liver health issues

• Vitamin deficiencies

• Inflammatory markers

• Lipid abnormalities

• Hormonal imbalance (where clinically appropriate)

This allows treatment plans to be tailored more intelligently rather than simply escalating doses or abandoning therapy prematurely.

What You Can Do If You’ve Hit a Plateau

If progress has slowed or stopped:

1. Review adherence and injection technique

2. Assess lifestyle factors honestly – sleep, stress, alcohol, smoking, activity

3. Review current medications that may affect weight

4. Consider clinical blood testing to identify hidden barriers

5. Reframe expectations – plateaus are part of long-term weight management

6. Adjust the plan rather than quitting

Weight loss medicines remain powerful tools — but they work best when integrated into a wider clinical strategy.

A Sensible, Individualised Approach

At Bramley Pharmacy, we support patients through structured clinical reviews, face-to-face consultations and optional blood testing where appropriate. Our aim is to ensure weight management remains safe, evidence-based and tailored to the individual — not driven by one-size-fits-all expectations.

If you feel your progress has stalled or you would like a clinical review, you can book a consultation or speak with our team for advice.