How to recognise if you’re developing a tolerance to Wegovy?

People sometimes call a plateau “tolerance,” but classic drug tolerance isn’t the main issue here. Signs to explore include hunger returning most days, cravings as frequent as before, or weight not trending down at agreed review points despite consistent dosing. Your team will check technique (hold time, site), missed doses, titration pace, meal structure, sleep, and interacting medicines. If you’re tolerating treatment but not seeing benefit, they may adjust the plan, hold a step longer, or confirm whether continuing is appropriate.

Understanding what “tolerance” really means

When people talk about “tolerance” to Wegovy (semaglutide), they often mean the feeling that the medicine isn’t working as strongly as before. In pharmacology, tolerance means the body adapting so that higher doses are needed for the same effect. NICE TA875, NHS England’s 2025 weight-management framework, and MHRA data show that this is not what happens with semaglutide. The medicine continues to activate GLP-1 receptors effectively; rather, the body’s response adapts as weight decreases and energy balance changes. Appetite can feel stronger again, not because the medicine has stopped working, but because the body is defending a new, lower weight.

The difference between a plateau and loss of effect

Weight loss is rarely linear. NICE and NHS clinical guidance explain that most users experience a plateau after the first six to twelve months. This plateau is part of normal physiology — the body reaches a point where energy intake and output balance. In the STEP and SELECT trials (Lancet Diabetes & Endocrinology, 2024), weight typically stabilised after an initial steep drop and then declined more slowly. NHS clinicians describe this as the body “resetting its thermostat.” The medicine still works, but the rate of loss naturally slows. Recognising this helps avoid unnecessary dose changes or discouragement.

What might signal a true issue

Still, if hunger, snacking, or cravings increase noticeably over several weeks, or if weight rises despite good adherence, it’s sensible to review the situation. NICE and SMC frameworks recommend structured assessments before assuming the medicine has stopped working. These reviews look at:

• Injection technique: whether the pen is held flat and long enough for full delivery.

• Dosing rhythm: missed or delayed injections can reduce effect.

• Titration step: some people benefit from holding a dose longer before escalation.

• Lifestyle alignment: meal timing, protein intake, hydration, and sleep quality all influence appetite control.

• Medication interactions: steroids, antidepressants, or antipsychotics can increase hunger or fluid retention.

A small tweak in one of these areas often restores steady progress.

The body’s adaptation process

As weight falls, metabolism slows slightly — a normal process called adaptive thermogenesis. The body becomes more energy efficient, burning fewer calories at rest. NICE and MHRA analyses note that this can create the impression of tolerance, but Wegovy continues to support appetite regulation and calorie control. NHS dietitians often describe this stage as “maintenance training,” where lifestyle consistency takes over from the medicine’s early momentum. Reinforcing protein intake, staying active, and prioritising good sleep help preserve muscle mass and offset the slower burn rate.

What clinicians check at review points

At follow-up appointments, NHS clinicians review several indicators to determine whether Wegovy is still effective:

• Weight trend: steady maintenance or gradual loss over three to six months.

• Appetite pattern: whether fullness and food interest are stable.

• Side effects: any change in nausea, reflux, or fatigue that might alter eating patterns.

• Injection adherence: accuracy, timing, and site rotation.

• Comorbidities: such as thyroid, kidney, or mood changes that could affect metabolism.

If all factors look correct but benefit has flattened, clinicians may extend a dose step, maintain the current level longer, or consider alternative strategies like nutritional or behavioural adjustments. NICE TA875 stresses that discontinuation is only considered when consistent review shows minimal benefit despite correct use.

When “tolerance” is actually technique

MHRA and NHS training audits show that many reports of “reduced effect” stem from simple technique errors. Removing the pen too early or injecting at an angle can leave part of the dose under the skin rather than absorbed. Rotating sites helps prevent thickened tissue (lipohypertrophy) that can slow absorption. Refresher training — even a five-minute demonstration — often restores results. NICE TA875 recommends re-checking injection technique annually or whenever weight loss slows unexpectedly.

The psychological aspect

Perceived “tolerance” can also arise when expectations are unrealistic. NHS behaviour-change teams often counsel that rapid early loss followed by slower, steadier progress is success, not failure. Comparing to early results can make normal slowing feel like regression. Recognising that semaglutide’s role is to support sustainable change — not constant weight loss — helps reframe expectations. Clinicians encourage focusing on health improvements such as energy, mobility, and blood pressure, not just the scales.

Evidence from long-term trials

In long-term studies, Wegovy’s effect on weight and appetite remained stable over time. STEP-5 (Nature Medicine, 2024) and SELECT (Lancet, 2024) showed sustained appetite suppression and metabolic benefit for up to two years without diminishing drug response. NICE TA875 and SMC analyses confirmed that any “tolerance” observed clinically reflects lifestyle and physiological adaptation, not reduced receptor activity. This evidence reassures both clinicians and users that continued benefit is achievable with consistent adherence and support.

When to consider adjustments

If genuine loss of benefit is suspected despite confirmed adherence and technique, clinicians might evaluate for factors such as new medications, hormonal changes, or underlying conditions affecting metabolism. In some cases, dose adjustments within the approved range or referral for specialist review may be appropriate. However, NICE and NHS guidelines emphasise that maintaining the same dose while reinforcing lifestyle strategies is usually more effective than escalation alone.

The essential point

Apparent “tolerance” to Wegovy is almost always a normal plateau or the result of practical factors, not true drug resistance. Regular reviews, correct technique, and consistent routines sustain long-term success. NICE, NHS, MHRA, and SMC guidance all agree: Wegovy continues to work when used correctly, but the body naturally slows as it adapts — that’s progress, not loss of effect.