Ozempic (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist widely prescribed in the UK for managing type 2 diabetes mellitus. Whilst the medication consistently improves glycaemic control and often leads to weight reduction, many patients wonder whether its effectiveness diminishes over time. Understanding how Ozempic works, why weight loss may plateau, and what factors influence treatment response can help patients and clinicians optimise long-term outcomes. This article examines the evidence surrounding Ozempic's sustained efficacy, explores common reasons for perceived reduced effectiveness, and provides guidance on when to seek medical review.

How Ozempic Works for Blood Sugar Control and Weight Loss

Ozempic (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for the treatment of type 2 diabetes mellitus. It works by mimicking the action of the naturally occurring hormone GLP-1, which plays a crucial role in glucose homeostasis and appetite regulation.

The medication exerts its therapeutic effects through several complementary mechanisms. Firstly, semaglutide enhances glucose-dependent insulin secretion from pancreatic beta cells, meaning insulin is released only when blood glucose levels are elevated. This reduces the risk of hypoglycaemia when used alone, though this risk increases when combined with sulfonylureas or insulin. Secondly, it suppresses glucagon secretion from pancreatic alpha cells, which helps prevent the liver from releasing excess glucose into the bloodstream. Thirdly, Ozempic slows gastric emptying, prolonging the time food remains in the stomach and leading to more gradual glucose absorption.

Beyond glycaemic control, Ozempic has gained attention for its effects on body weight. The medication acts on appetite centres in the hypothalamus, reducing hunger and increasing satiety. Clinical trials have demonstrated that patients using semaglutide typically experience significant weight reduction alongside improvements in HbA1c levels. The SUSTAIN clinical trial programme showed average weight loss of 4–6 kg over 30–56 weeks in people with type 2 diabetes.

It is important to note that whilst Ozempic is licensed for diabetes management in the UK, a higher-dose formulation (Wegovy, also semaglutide) has been specifically approved for weight management in certain patient groups. NICE guidance (TA875) recommends Wegovy within specialist weight management services for eligible patients, while NICE guideline NG28 covers Ozempic use in type 2 diabetes management.

Why Weight Loss May Plateau During Ozempic Treatment

Many patients using Ozempic experience a weight loss plateau after an initial period of steady reduction, which can understandably cause concern. However, this phenomenon is well-recognised in clinical practice and does not necessarily indicate that the medication has stopped working.

The human body possesses sophisticated metabolic adaptation mechanisms designed to defend against sustained weight loss. As body weight decreases, basal metabolic rate typically declines, meaning fewer calories are required to maintain basic physiological functions. Additionally, hormonal changes occur that can increase hunger signals and reduce satiety, making it progressively more challenging to maintain a caloric deficit. Research has shown that weight loss triggers compensatory increases in ghrelin (the 'hunger hormone') and reductions in leptin (which signals fullness), creating a biological drive to regain lost weight.

With Ozempic specifically, patients often experience their most dramatic weight loss during the first 3–6 months of treatment, particularly during the dose escalation phase, though this varies between individuals and depends on dose and adherence. As the body adjusts to the medication and reaches a new equilibrium, the rate of weight loss naturally slows. This does not mean the drug has become ineffective—rather, it continues to provide appetite suppression and metabolic benefits that help maintain the achieved weight loss.

Clinical trial data demonstrates that whilst the steepest weight reduction occurs early in treatment, patients typically continue to lose weight gradually or maintain their reduced weight over extended periods. The STEP trials showed that weight loss continued up to 68 weeks, albeit at a progressively slower rate, though it's important to note these trials used semaglutide 2.4 mg (Wegovy) for weight management rather than the lower Ozempic doses. It is also worth noting that Ozempic's primary indication remains glycaemic control in type 2 diabetes, and its effectiveness for this purpose generally remains stable over time, even when weight loss plateaus.

Factors That Can Reduce Ozempic's Effectiveness

Whilst Ozempic generally maintains its therapeutic efficacy over extended periods, several factors can influence an individual's response to treatment or create the impression that the medication is no longer working as effectively.

Dietary and lifestyle factors play a crucial role in treatment outcomes. Patients who gradually increase their caloric intake or consume calorie-dense foods may counteract the appetite-suppressing effects of semaglutide. Similarly, reduced physical activity levels can diminish weight loss progress. The medication works most effectively when combined with sustained lifestyle modifications, including a balanced diet and regular exercise as recommended by NICE guidance (NG28) for type 2 diabetes management.

Medication adherence is another important consideration. Ozempic is administered as a once-weekly subcutaneous injection, and missed doses can reduce therapeutic effectiveness. Proper injection technique and site rotation between the abdomen, thigh, and upper arm are recommended to ensure correct subcutaneous administration and minimise local reactions.

According to the Ozempic SmPC, anti-drug antibodies have been detected in a very small percentage of patients in clinical trials, but there is no evidence that this impacts clinical efficacy or safety for most people. The immunogenicity of semaglutide is considered very low.

Regarding medication interactions, the Ozempic SmPC notes few clinically relevant interactions. However, patients taking warfarin should have their INR monitored when starting semaglutide. Importantly, when Ozempic is used with sulfonylureas or insulin, there is an increased risk of hypoglycaemia, and dose reductions of these medications may be necessary.

Disease progression in type 2 diabetes—particularly declining pancreatic beta-cell function—may necessitate treatment intensification regardless of GLP-1 receptor agonist therapy.

Finally, psychological factors such as 'medication fatigue' or reduced motivation can affect adherence to both the medication regimen and accompanying lifestyle measures, indirectly reducing treatment effectiveness.

What to Do If Ozempic Stops Working as Well

If you feel that Ozempic is no longer providing the same benefits for blood sugar control or weight management, it is essential to consult your GP or diabetes specialist rather than discontinuing treatment independently. A thorough assessment can identify the underlying cause and guide appropriate management.

Your healthcare provider will likely begin by reviewing your current regimen. This includes confirming that you are taking the correct dose. Ozempic is typically initiated at 0.25 mg weekly for 4 weeks (for tolerability), then increased to 0.5 mg. After at least 4 weeks, the dose can be increased to 1 mg weekly if needed for glycaemic control. A maintenance dose of up to 2 mg once weekly may be considered if additional glycaemic control is required, according to the UK SmPC. They will also assess your injection technique, site rotation practices, and medication storage, as improper handling can reduce drug potency.

Monitoring key clinical parameters is essential. Your doctor will check recent HbA1c levels to objectively assess glycaemic control, review home blood glucose readings if you perform self-monitoring, and evaluate weight trends over time. This data provides a clearer picture than subjective impressions alone. If glycaemic control has deteriorated, NICE guideline NG28 supports treatment intensification, which may involve increasing the Ozempic dose (if not already at maximum), adding complementary diabetes medications such as SGLT2 inhibitors or metformin, or considering alternative GLP-1 receptor agonists.

For patients primarily concerned about weight loss plateau, healthcare professionals will typically reassess lifestyle factors. This may involve referral to a dietitian for nutritional counselling, discussion of physical activity levels, and exploration of behavioural strategies to support sustained weight management. Some patients benefit from structured weight management programmes or psychological support to address emotional eating patterns.

If you are taking Ozempic alongside sulfonylureas or insulin, your doctor may need to adjust these medications to reduce the risk of hypoglycaemia.

When to seek urgent medical attention: If you experience severe, persistent abdominal pain (with or without vomiting) that could suggest pancreatitis, stop taking semaglutide and seek urgent medical attention. Contact your GP promptly if you experience persistent hyperglycaemia (blood glucose consistently above 15 mmol/L), positive ketones, vomiting or dehydration, or symptoms of diabetic ketoacidosis (excessive thirst, frequent urination, confusion). Call NHS 111 or 999 for severe symptoms. Also seek urgent care for symptoms of gallbladder problems (right upper abdominal pain, fever, jaundice).

If you experience side effects from Ozempic, you can report them via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk.

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