Recent Advances. Weight Management Pt2

Medication has become the hot topic in the control of body weight. For decades we have seen different drugs come and go – none making any significant impact. Suddenly, with GLP-1 agonists, this has all changed.

The glucagon-like peptide 1 (GLP-1) agonist, semaglutide, was the market leader. This group of drugs was developed as medication for the control of type 2 diabetes (T2DM) and semaglutide was found to produce significant weight loss among it takers. Trials in non-diabetics found the same and suddenly this has become a very hot topic indeed. There is a huge appetite for achieving weight loss with minimal pain and disturbance of normal lifestyle!

Semaglutide

The effects

Semaglutide is not well absorbed by mouth and is given by weekly injection, usually self-administered. It is marketed by the Danish company, Novo Nordisk and has two trade names.  Ozempic is used for treating T2DM and Wegovy for weight control – the constituent drug, semaglutide is the same for both. It seems to work by slowing stomach emptying, thus increasing and prolonging the period of appetite satisfaction. In clinical trials the effect has been between 15 and 20% weight loss over three to six months and over time this loss is sustained – for up to three years in one trial of 1,000 patients. Other benefits have included sustained reduction in  diabetic markers and improvements in heart function in some cardiac patients. One trial indicated a reduction in stroke and heart attacks by up to one fifth. Earlier this year The National Institute for Health and Care Excellence (NICE) approved the use of semaglutide for those with a BMI of at least 35 with a related comorbidity, alongside a diet and exercise plan. It recommended that the drug should not be continued beyond two years.

The side effects

The manufacturers admit to minor abdominal complaints including pain, nausea and constipation. More serious effects have been reported and include pancreatitis (inflammation of the pancreas), stomach paralysis and thoughts of suicide and self-harm.

The claims

The development of Wegovy for obesity has been hailed as a “gamechanger”. It has also been recommended as part of the cardiologist’s armamentarium. Novo Nordisk has claimed that widespread use should lead to long-term money saving as well as the saving of lives. “Affording the cost? …We can’t afford not to” is another claim.

The downsides

Semaglutide only works as long as it is taken. When the drug is stopped, weight is usually regained so that within a few months  most are back to near their previous weight.  Unfortunately it is not only fat which is lost but also muscle mass which makes up about a quarter of the total weight lost. With weight regain, it is possible that the fat is replaced but not the muscle leaving the individual even less healthy than before.

It has therefore been suggested that this treatment could or should not be limited to two years but  should be for life. Indeed there may be little point in prescribing it in the first place unless the taker is prepared for it being a lifetime drug.

Supply and demand

The demand for Wegovy has grown to the extent that it exceeds supply and there are shortages in many countries. It has been proposed that its use be rationed to allow enough semaglutide to be available for diabetics. The shortage has been fuelled by its use among those with mild obesity and those who are just a bit overweight. Even those with normal BMIs have been known to take it for cosmetic reasons. The term “Wegovy face” refers to the resulting changes with more lines and wrinkles, loose and sagging skin due to loss of fat cells and a hollowed-out appearance.

Financial costs

The price of Wegovy varies widely around the World – up to $1,400 per month in the US, $252 in Norway and only $95 in Turkey. The  cost in the UK is about £300 per month.

Wegovy has been a great little earner for Novo Nordisk. Shares in the company have skyrocketed and made it the most profitable pharmaceutical company in Europe. The predicted worth of the weight-losing drug market is expected to reach $100 billion by the end of the decade.

Weight cycling – beware!

The widespread use of GLP-1 agonists will result in the phenomenon of weight cycling – losing weight, putting it back back on and then losing it again with resumption of medication. This is the problem with all diet related treatments for obesity if exercise is not included in the weight losing strategy. In the weight loss section of recycling both fat and muscle is lost. In the weight regain section only fat is replaced – there is progressive loss of muscle mass with all its consequent health problems.

What next?

With such profits to be made it is not surprising that a number of other Big Pharma companies are lining up with their own, sometimes even more effective, versions. The race leaders at present include Roche’s tirzipatide (Mounjaro) and Eli Lilly’s retatrutide (yet to receive a trade name). I am sure that I will be writing more about these in the coming months.