Semaglutide for weight loss

Semaglutide, a medication previously used for diabetes, has this week been approved by the National Institute for Health and Clinical Excellence (NICE) for use in weight loss. I am optimistic that it is going to be a game-changer in the management of obesity. The reason is that I have already been using it off-label for my obese patients with great success.

That may sound strange coming from a doctor who likes to treat people by avoiding medication whenever possible and optimising their lifestyle. The problem with changing lifestyle is that it only works if people manage to stick with it. The natural inclination is to think that this is entirely a matter of choice. As a result, overweight people continue to be stigmatised as being weak-willed or not having self-control. The problem with this thinking is that it is completely untrue; unfairly so.

Increasing weight is associated with hormonal and metabolic changes that result in people continuing to feel hungry despite eating sufficient food. Their appetite off-switch does not work properly. Worse still, they crave unhealthy and high calorie foods because their brain tells them that they are still starving. Part of the hormonal change is insulin-resistance which makes weight loss more difficult.

How does semaglutide work?

Semaglutide is a Glucagon-Like Peptide-1 (GLP-1) analogue. As its name suggests it behaves the same as the hormone GLP-1 that we all have in our bodies and which is released by our small intestines. The action of GLP-1 is to:

Delay gastric emptying and reduce small intestine motility

You feel full after eating for a longer period and consequently eat less.

Reduce appetite

Appetite is reduced directly by the effect of GLP-1 on various parts of the brain. You feel less hungry.

Release insulin from the pancreas

GLP-1 increases release of insulin from the pancreas in response to glucose and reduces the release of glucagon, a hormone which has the opposite effect. This means that you become more insulin sensitive. Overweight people tend to have insulin resistance which makes weight loss difficult so this is an important effect.

Evidence that semaglutide works for weight loss: the STEP 1 study

What was the study about?

The STEP 1 study set out to compare weight loss in 2 groups of people; one group that was randomised to use semaglutide and another group that used a placebo injection.

Both groups:

• Received lifestyle advice
• Reduced their calorie intake by 500 kcal daily
• Exercised (walking) for 150 minutes per week; e.g. 30 minutes, 5 days per week

Who were the participants?

There were 1,961 participants who had a BMI of 30 or more, or 27+ with one or more health conditions.

Most participants were white (74.1%) and female (75.1%).

The average weight of the participants was 105.3 Kg (16 stone 8 lb), average BMI 37.9, and average waist circumference 114.7 cm (45 inches).

Both groups contained people of similar ages, starting weights and demographics.

How long did the study go on for?

68 weeks (16 months)

What was the final result?

Average weight loss was much greater in the semaglutide group than the lifestyle-only intervention group.

The semaglutide group lost on average 15.3 Kg (14.9%) or 2 stone 5.7 lb from their starting weight compared to just 2.6 Kg (2.4%) or 5 lb in the lifestyle-only group over the 16 month period.

The semaglutide group also had greater improvements in waist circumference, blood pressure, cholesterol, HbA1C (blood glucose control), a marker for inflammation CRP, and physical and mental wellbeing. In the semaglutide subpopulation that had their body composition measured, they lost significantly more total fat and visceral fat, and increased the proportion of lean muscle mass.

What were the side-effects?

The main side-effects were equally common in both groups but gastrointestinal side-effects of nausea, diarrhoea, vomiting and constipation were more common in the semaglutide group (74.2%) than the placebo group (47.9%). Most gastrointestinal side-efffects were transient, mild to moderate in severity and subsided with time.

Serious side-effects were more common in the semaglutide group (9.8%) compared to the placebo group (6.4%). The difference was due to greater gastrointestinal and hepatobiliary side-effects (e.g. gallstones) in the semaglutide group. More people stopped treatment in the semaglutide group (7%) compared to the placebo group (3.1%). These were mostly due to gastrointestinal side-effects.

Take home messages

Semaglutide is amazingly effective for weight loss when combined with lifestyle changes, much more than just lifestyle changes alone.

The weight loss is over a period of 16 months.

Three-quarters of the people in the study who took semaglutide had mild gastrointestinal side-effects. A small number of people had such severe side-effects that they had to stop taking it.

Unanswered questions

Will semaglutide be equally effective in people who are not like the study population who were mostly white and female; i.e. will it work in non-white races and in men?

What are the long term effects after 16 months? This has not been studied.

Who should consider treatment?

You should consider treatment if you have a:

BMI > 30 with no other associated medical problem

or

BMI > 27 and having an associated medical problem such as high blood pressure, high cholesterol, sleep apnoea or a heart problem.

How can you start weight loss treatment with semaglutide?

Book a weight loss appointment with me at Prime Health in Weybridge, Surrey. If you live elsewhere in the UK, then you can book a telephone or video appointment.

Appointments are monthly to begin with for the first 6 months and include an assessment of your medical history, lifestyle counselling and monitoring of your progress. During this phase, the dose of semaglutide will gradually be increased and your medical condition and side-effects monitored.

The semaglutide injections will be sent to your home via e-Medicina pharmacy. Patients will make payment to e-Medicina for the injections directly.

Once a stable dose of semaglutide is reached, the frequency of appointments can be reduced for the duration of the treatment depending on your progress, general health, and the existence of any medical conditions that may need monitoring.

What is the cost?

The cost of treatment will include the cost of doctor appointments plus the cost of semaglutide injections. At the time of writing, the cost of semaglutide is around £100 per month.

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How to use semaglutide injections

Semaglutide is a once-weekly injection into the fat around your belly. It is straightforward to use. Watch this video to find out how. Please note that Ozempic is a brand of semaglutide and yours may be a different brand.

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