By Dr Amer Sheikh • February 12, 2022 • No Comments
You may have heard of some amazing weight loss injections and wanted to find out more about them. Semaglutide, brand name Ozempic or Wygovy, a medication previously used for diabetes, has been approved by the National Institute for Health and Clinical Excellence (NICE) for use in weight loss. I am convinced that semaglutide injections are 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 obesity 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. In fact, if you had asked me about weight loss injections a few years ago, then I would probably have rolled my eyes. However, 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 enough 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.
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:
You feel full after eating for a longer period and consequently eat less.
Appetite is reduced directly by the effect of GLP-1 on various parts of the brain. You feel less hungry.
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.
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:
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.
68 weeks (16 months)
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.
Semaglutide has been on the market since 2017 and has been in use in the UK since 2019 for diabetes. We, therefore have a good idea about its side-effects, but not the long-term effects since it is a new medication.
The main side-effects in the study 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.
Mild acute pancreatitis was reported in three participants in the semaglutide group (one participant already had a history of acute pancreatitis, and the other two participants had both gallstones and pancreatitis); all recovered during the trial period. There was no difference between groups in the incidence of benign and malignant tumours. Animal studies have shown an increased risk of thyroid cancer but this has not been demonstrated in humans.
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.
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?
This has partly been answered in the Step 6 trial which showed effective weight loss in East Asians. The Step Teens trial also showed that semaglutide was effective in the 12-17 age group.
What are the long-term side-effects?
You should consider treatment if you have a:
BMI > 30 with no other associated medical problem (Obesity is defined as a BMI >30)
or
BMI > 27 and having an associated medical problem such as high blood pressure, high cholesterol, sleep apnoea or a heart problem.
We now know what happens when you stop treatment with semaglutide following the Step 1 Trial Extension. About 300 patients in the original study were followed up for 1 year after stopping semaglutide weight loss injections. On average, they regained two-thirds of the weight that they had lost, indicating that obesity is a persistent condition.
Although this sounds disappointing, these patients were taking 2.4mg semaglutide and were on a reduced calorie diet. Once they stopped semaglutide injections, they reverted to their previous pattern of eating.
My experience over the past year has shown me that patients rarely need such a big dose of semaglutide to reach their target weight that was used in the original study. Most of my patients are taking a maximum of 1mg each week. During the period that they are taking the weight loss injections, I make suggestions to modify their diet so that they are more easily able to maintain their weight loss when they stop the injections. So far, some of my patients are able to stop semaglutide completely, and some need to continue taking a reduced dose to maintain their weight loss.
The cost of semaglutide injections bought privately can be anything up to £160 per month for one pen. Each injection pen lasts 4 weeks.
Where can you buy semaglutide injections? Many people have been buying the injections online and administering it themselves without support from a qualified clinician. I would discourage such a practice as semaglutide is still a relatively new medication and, like all medication, needs to be started and followed up by a doctor. This is especially true if you have any medical problems or if you are taking any other medication.
I have a number of patients that I follow up regularly. The cost of treatment includes the cost of an appointments plus the cost of semaglutide injections. At the time of writing, the cost of semaglutide is around £100 per month when ordered through our partner pharmacy.
Semaglutide comes is a range of tablet doses, 3m, 7mg and 14mg under the brand Rybelsus which is for diabetic patients. Unfortunately, there is not much effect on weight loss at these doses.
A study has recently been published which shows that semaglutide tablets at a dose of 50mg do produce a weight loss of 15% which is equivalent to the injections. No doubt a 50mg dose will be available in the future but no such dose exists at present.
You may have heard in the news that semaglutide has been very difficult to get a hold of because of supply issues. Novo Nordisk, the company who makes it issued a statement that supply issues will continue until the end of 2024. The whole World seems to be taking it.
The problem is not with the supply of the medicine but with the plastic pen device that it comes in. They can apparently not make enough to keep up with demand. This issue may be solved if the semaglutide 50mg tablet gets approval.
At my practice, there are times when patients cannot get the dose of semaglutide that they need. We deal with this in a number of ways which aim to maintain the weight loss that they have already achieved until the pharmacy is able to source more supply. This may involve taking a lower dose or taking tablets temporarily.
Please book a weight management 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 few 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.
Semaglutide is a once-weekly injection into the fat around your belly and is straightforward to use. Each pen contains 4 doses, once per week and therefore also comes with 4 tiny needles. Watch this video to find out how. Please note that Ozempic is a brand of semaglutide.
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