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Semaglutide for weight loss: is it a miracle drug?

There is a lot of press recently on semaglutide as the answer to everyone’s prayers regarding weight loss. When a drug earns an entire segment on 60 Minutes, you know it’s a hot topic.

So what exactly is semaglutide, how effective is it, what are the side effects, how much does it cost and how long do you need to stay on it?

What is semaglutide?

Semaglutide is in a drug class called GLP-1 receptor agonists. In this category are several including semiglutide (trade names Wegovy, Ozempic, and Rybelsus) as well as liraglutide (Victoza and Saxenda).

The drugs work by mimicking peptides (small protein molecules) that stimulate glucose-dependent insulin secretion. Essentially, they trigger the cells in your pancreas to release more insulin. They also slow gastric emptying, so you feel full for longer, and they reduce glucagon release, making sure your blood glucose level does not drop too low. Semaglutide also leads to a reduction in food intake, so you eat fewer calories—thus its use as a weight loss drug.

These drugs were initially developed to treat diabetes, but solid studies have also found that they have a profound impact in reducing weight, sometimes between 15 - 20%. Generally, any weight reduction over 5% weight loss is considered significant.

How effective is semaglutide?

In studies that compared semaglutide to lifestyle interventions, something we will get to later, this drug is very effective.

In the initial large study, 1,306 people were randomly assigned to receive semaglutide weekly, while another 655 were given a placebo. After tracking participants for more than a year, those who had been getting semaglutide had lost an average 14.9% of their body weight, compared to the 2.4% lost by those getting the placebo.

The now standard dose of semaglutide is 2.4 mg administered by injection weekly. Liraglutide is administered daily by injection. Both were effective in controlling diabetes while semaglutide showed more weight loss and was a weekly vs. daily injection.

A summary of 14 recent studies that compared various GLP-1 drugs found the drugs to be effective at helping to manage blood glucose levels, with semaglutide being the most effective at generating weight loss.

Samaglutide side effects

As can be expected due to the drug’s focus on your gastrointestinal tract, the most common side effects are nausea, vomiting and diarrhea. That said, only about 5% of patients had to withdraw from the clinical trials due to severe side effects.

The Mayo Clinic lists “less common” side effects to include belching, feeling bloated, gaseous stomach pain, heartburn, passing gas, recurrent fever, and stomach discomfort.

How much does it cost?

Now we get to the more challenging part of the discussion.

The drug maker of semaglutide, Novo Nordisk, must certainly be happy. The average daily cost for those with insurance is approximately $200/month. Without insurance, it is $1,200 per month.

As most may surmise, this is not a first line therapy drug so the likelihood is that you will have significantly more out of pocket exposure. In addition, there are certainly ‘specialists’ that are advertising this as part of their weight loss program.

How long do I need to be on it?

For life. Yes, you heard that right. Basically, once on this drug you can never come off, as the evidence is you will gain back a significant amount of the weight lost as well as the metabolic benefits.

From a drug maker’s perspective, this is a perfect drug. It treats the problem but never fixes it, and so requires lifelong therapy.

The longer view

It is interesting to see the rise in obesity over the last 40 years. From the CDC:

Obviously, our genetics have not changed significantly since 1960, so we must conclude that environmental factors are driving this 300% increase. It is all about the food we eat (ultra-processed vs whole foods) and change in movement patterns (more office work, less overall movement) that accounts for that change.

In our modern way of thinking then, of course and unfortunately, we must need a pill for this problem. I have no doubt there is a small subset of people, as highlighted in the 60 Minutes episode, who follow good lifestyles habits and yet who are still struggling with their weight. But I am highly skeptical that the solution to the overall obesity epidemic is to place most people in this category on a medication that will be required for the rest of their lives.

And just as unfortunate as well as worrisome is the rising rates (quadrupling) of childhood obesity. From the NIH:

So, as expected and as we have seen with powerful psychiatric medications, there will be calls for these drugs to be used in children. Remember, these drugs are being used to treat Type 2 Diabetes, not Type 1 where the immune system has attacked the cells in the pancreas destroying the ability for your body to make insulin.

In the vast majority of people and especially children, Type 2 diabetes is a completely reversible disease when a structured holistic approach using food (and movement) as opposed to medicine is taken.

There have been many reasons for the rise in obesity, including the increase of high fructose corn syrup into sugar sweetened beverages, less general physical activity over time and increased calorie density with a simultaneous decrease in nutritional density (the empty calorie hypothesis). Unfortunately, many of these trends are made worse in lower socioeconomic groups where cheap calorie dense (ultra-processed) foods provide a more short-term cost-effective solution when deciding where to spend limited dollars.

Absent a change in these drivers the background forces driving obesity will not change. No drug, regardless of effectiveness, will bend the curve of obesity leading to type 2 diabetes, increased cardiovascular disease, cancers and dementia.

The only effective solution for the vast majority of Americans, and now sadly the world, is an awareness of these drivers and concentrated effort and focus to minimize them as well as maximize health and longevity.

It is certainly a less glamorous approach but one that leads to better long-term results.

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