Obesity drugs coming to market

Simiglutide plus another ingredient may be a big deal. Details in the study.



Obesity drugs have been on the market for millenia, real food!

The Captain


Actually, it’s a pretty big deal even by itself.

From what I can gather (from endocrinologists/obesity specialists I follow online) it’s an example of those serendipitous observations that have merit when studied. Basically, unexpected weight-loss in the target group … overweight/obese T2D…seemingly with no behaviour change.

My husband is particularly interested as it ties in quite closely with his current area of research…oxygen-nutrient mismatch in the liver and NAFLD.

Problem is, it’s now being pushed right left and center for “weight loss” and if you do an internet search pretty much everything that pops up is an ad for your local weight-loss clinic. It’s apparently now in short supply.


Semaglutide was developed by Novo Nordisk and approved by the FDA for subcutaneous injection in December 2017. The tablet formulation was approved for oral administration in September 2019.

Novartis manufactured bimagrumab but Versanis Bio is running a Phase 2b study to assess the safety and efficacy of bimagrumab alone and in combination with semaglutide for the treatment of obesity. The full-scale clinical trial (very expensive) is needed for FDA approval of any drug prescribed to treat a specific disease – in this case, obesity. That’s serious business because 40% of the U.S. population is obese so the market is huge.

Versanis is a privately held, clinical-stage biopharmaceutical company. It’s a portfolio company of Aditum Bio, Atlas Venture, and Medicxi. The company’s lead asset is bimagrumab. I don’t know what they mean by “lead asset.” Does Novartis still do the manufacturing?





And the ever present question, what happens when you stop taking the drug(s). The answer will most likely be to regain the weight. And yo-yoing your weight loss/gain is more harmful.

Ultimately, if you don’t want to take drugs forever, you have to make lifestyle changes either by paying more attention to what you eat and/or by being more active. Unfortunately, too many just want to take a pill/shot/whatever.


60 minutes ran a piece a couple of weeks ago on obesity. They talked to doctors and scientists who are approaching obesity as a disease rather than a lack of self-control.

I’m not qualified to make comments on the science, but I did spend 40+ years of my life with an obese person. My observation is that obesity may not not necessarily be connected to the quantity or quality of food eaten.

Here’s the piece. I think it is well worth the time to both read and watch.


There is no salient difference between the two. Whether you consider “obesity” to be the disease or “lack of self-control” to be the disease. Humans are very complex organisms, and if somehow the pathways in the brain are “broken” causing that lack of self-control, that too is a disease.

I’ve tried to explain this many times, but people just don’t get it for some reason. It’s essentailly a simple arithmetic problem. The main issue is that it’s not observable. But it IS directly connected to quantity (and perhaps to quality as well). The reason it’s not observable is because the difference in quantity required for obesity is tiny, even minuscule, on a day to day basis. Would you even notice if the obese person in your life uses an extra teaspoon (or packet) of sugar in their morning coffee each day? No! It’s not like they are regularly having an extra serving of food, and they’re not eating sweets on the sly, and they don’t have a secret stash of chocolates. That is all they do differently than an equivalent person, that one extra packet of sugar in their coffee. If you look solely at calorie input, how much weight does that tiny change in diet add over 20 years? Any ideas? If you multiply it out, it adds more than 32 pounds!!! In a typical 120 pound female, that’s already obese. Now what if they also have an afternoon coffee the way they like it? That’s added almost 65 pounds over 20 years! Imagine that, no overeating, no out of the ordinary sweets, nothing observable on a day to day, or week to week, or month to month basis, yet still they are gaining a pound or three every year for two decades.

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[quote=“MarkR, post:7, topic:86548, full:true”] Now what if they also have an afternoon coffee the way they like it? That’s added almost 65 pounds over 20 years! Imagine that, no overeating, no out of the ordinary sweets, nothing observable on a day to day, or week to week, or month to month basis, yet still they are gaining a pound or three every year for two decades.

Well this is the simple mathematical model that you get from imagining a weight/fat gain of “x” over “y” number of years and throw in the 3,500 Cals in a pound of fat. The implication being that all it takes is reducing net energy intake by just a few Calories a day…easy peasy. Thing is, generally speaking and pathology aside, most overweight/obese people didn’t gain their excess fat at a slow and steady incremental pace.

A good many women, for instance, gain really large amounts of weight during pregnancy…eating for two/insatiable appetite etc…and resolve to take it off . Except, they don’t quite manage it. A second pregnancy and wash, rinse, repeat…

We’ve just come out of the traditional American gorge-fest known as The Holidays with opportunities available (and taken) for overeating + +…and then some. Next comes the New Year Resolutions which are just coming up to burn out (just turned the page in my runner’s training log and realised we’re halfway through January, already)

Heaps of other examples that folk with.more experience than I have in getting fat could give but, to use a common phrase…“It’s a bit more complicated than that”.


Interesting in my case the lack of self control is the disease.

But that is not a medical billable.

Noom works well…or as well as you work it.

I lost 50 lb and have kept off 46 of it for over 1.5 years. My sister lost 28 lb and has kept off 25 lb of it. The savings for each of us in medical bills alone is the cost of a middle class home in all likelihood. The quality of life for both of us has improved dramatically.

Better doctors wont be prescribing weight loss drugs. Unless you are on death doorstep and have to lose the weight. There are different patient problems.

Casual use of weight loss drugs is a huge mistake.

BTW casual use of sleeping pills is also the same sort of massive mistake.

This was NOT my implication at all. I was simply illustrating that excess casloric intake isn’t easily observed. Furthermore, at this point, typical “dieting” (restricting caloric intake) has been shown to not work over the long-term. I also believe that repeated bouts of restricted caloric intake has the opposite effect in many/most people (the studies will likely catch up to my belief at some point). I also think that the only way to maintain weight loss (after your body has somehow been “broken”, possibly insulin related or maybe something else research will show someday) is to change overall style of eating in various ways. Basically you have to retrain the body/brain how to eat differently.

This is flat wrong. Obesity, except in rare pathological cases, is indeed steady and incremental. Even among kids that are obese, it has been shown that it happens over a decade plus (a pudgy toddler isn’t considered obese").

And among the population at large, it’s been a steady and incremental phenomenon. Furthermore, women who have been pregnant only have a slightly higher incidence of obesity, it isn’t as vast a difference as you seem to indicate. Not to mention that less than 25% of the population have had two or more full-term pregnancies.

All those things - holidays, failed New Years resolutions, etc are basically excuses that we provide for ourselves, but they don’t stand up to scrutiny because they aren’t really causes, they are symptoms of the overall progression of weight gain over time. Maybe more later, heading out to watch a movie.

Here’s a graphic I just happened to see recently.

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Looking at those maps the biggest difference is lights out at bedtime.

The rest of it is just a shuffling of other bad factors in the food etc…

It is not what is on the cellphone screen as much as the screen is lit up.

Well, from the graphic you’ve posted, it’s pretty clear that weight gain in the overweight hasn’t been achieved in a subtle way or to the tune of a few extra Calories each and every day over an extended period. Quite the reverse.

Even casual observation such as walking round a local mall, you don’t have to be particularly hawk eyed to see that the food court, for instance, is almost full of folk chowing down on lumberjack sized meals at 10 am or families strolling around with slices of pizza or other easily transportable sources of energy dense food. Almost all seriously overweight or borderline obese…and surprisingly young. Quite possibly a good few would also be unwilling to accept that their personal energy intake isn’t particularly excessive.

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I gained my weight over summer where I was forced to eat copious amounts of Tri-tip and wash it down with beer. I didn’t even enjoy one bit of it.


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Clearly, you didn’t watch or read the article I linked.

There is a huge difference between a disease and a lack of self control.

A disease can be cured or managed with various medical interventions. If you have Type 1 diabetes, you can exercise all the self control you want. But your body still will not produce insulin. You need medical intervention to manage that disease. Yes, some self control will help, but it will not be sufficient.

The 60 Minutes piece presented the position that obesity is often the result of a disease, and as a disease it needs medical intervention, not just telling people to eat less and exercise more.


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I am not commenting on the video or article. I am saying that both physical disease (diabetes, for example) and mental disease (lack of control, for example) are biological and are physical at their core. Insulin issues, serotonin issues, gut bacteria issues, or whatever causes a problem is a “disease” of the human body.

It’s not at all surprising. At age 3 we plop them in front of the TV playing a video … with snacks, of course … to keep them occupied. At age 5 we hand them a tablet to watch videos … with snacks as usual … to keep them occupied. At age 9 or 10 we get them a phone … which keeps them occupied for hours a day. As teens they gorge on social media instead of real socializing (that requires walking around and going to places with friends). At 18 they go to college, live in nice dorms with plenty of food … with a car and/or an uberlyft account so they don’t need to walk much. Suddenly in their 20s … boom they’re obese and spending too much time at the food court. I wonder why? Guess what? They’ve been “training” in the art of obesity for 20 years!


Although the examples given in the piece sound persuasive for “the obesity as disease” model, I don’t think it reaches quite the level of type1 diabetes for most.

For sure, with increasing adiposity, the body undergoes a number of metabolic changes that make subsequent attempts at weight loss and maintenence difficult but I doubt it’s quite as extreme as some of the examples given for most.

For instance, the idea of the body defending a set point/resisting weight loss is true to a certain extent but the implication here is that this mechanism can somehow create energy out of thin air. I’m thinking about the example of the obese young woman who appears to work out on a daily basis and eat very little. This doesn’t sound a very plausible explanation of why someone is remaining obese.

Situations like this usually hinge on a self reported workout regimen and eating plan … and individuals are notoriously unreliable at this sort of self assessment. That’s not to say they’re lying … even to themselves…but there are metabolic studies where subjects are under close scrutiny with specially prepared meals for controlled energy intake and the sort of technology that can measure energy expenditure with greater than 99% accuracy. Without fail these confirm that the body obeys the laws of thermodynamics.


But a few posts earlier you were arguing that the slow and steady path to obesity wasn’t easily observable and the result of just a few extra Calories daily over an extended period…65lbs over 20 years was your example

It’s one and the same. Those of us who grew up without constant “screens” (just using that as a shorthand, there are myriad things that enter into the equation) also take many years to work our way up the obesity ladder … relatively small amounts of extra food (not noticeable to an observer of an individual) … and relatively small amounts in decrease of activity (hardly noticeable for an individual, but completely noticeable in society, just stand at the stairs and escalator by a metro/subway system and watch 98% line up for the escalator and 2% use the stairs) slowly result in obesity.

In short, it is not easily observable in an individual, but it is observable across society.


Hardly. In fact, as you go on to point out, it’s the very opposite.

My office manager articulated an example well over 20 years ago. I got back to the office after my lunchtime visit to the gym and she was opening the mail…

“Look at this, Dr N…don’t these meals look great?”

Well, yes they did. Lovely examples of culinary art so it was obviously an ad for a recipe book. Now I love recipe books. Don’t do much with them, mind…but they do look good on my kitchen shelves. Turns out that it was for the South Beach Diet cookbook. I asked why it was necessary to make the food so enticing for folk who don’t need much temptation to eat (only half facetiously)

“Pffft, you,” she said “If everyone ate like you, no one’d get fat in the first place”

There you have it pretty much for most. Folk who follow weight/fat loss diets successfully do so with varying measures of mindfulness and accountability and, for as long as this is maintained, so is the weight loss. One difficulty is that the habits of excess energy consumption are often so longstanding, keeping this degree of dietary surveillance for long enough for mindful eating to become a default is just plain hard (darn near impossible, I’d imagine, if folk are unwilling to accept the concept of energy balance as it pertains to them … and there’s a cottage industry trying to encourage this notion) This is without all the hormonal responses etc that kick in to maintain what the two physicians in the 60 minutes piece call the “set point”. Both of these obesity experts are advisors to the manufacturer of these weight loss drugs, BTW (according to the article) and I imagine are likely to be more inclined to argue the “obesity as disease” model.

I tend to think of the 4 stages of competence model in regard to the behavior change necessary. I think it holds water equally well for weight management as it does for prevention of dental caries and periodontal disease…or better yet, learning to drive a stick shift.

Feel free to doubt all you want. That doesn’t mean your doubts are correct.

I don’t see that. No one is implying that we can create energy. Instead, the mechanism is probably efficiency.

When there is excess food available, our bodies can store the excess as fat, or use up the energy less efficiently, or even extract less than all of the energy from the food consumed. The disease comes in when the body doesn’t limit the storage of excess energy rather than using it for a higher base metabolism or simply discarding the excess energy as waste.

The problem with simple calories in vs out is that not all of the calories in are converted to useful energy. Some people convert more of the calories in to usable energy, and some less. If you are one whose body extracts more of the calories consumed, you will always have weight problems. If your body extracts less, you won’t have a weight problem.

Maybe I’m arguing for a genetic issue more than a disease. But in either case, I believe that approaching the issue with an open mind and compassion is far more likely to be successful than just telling people to eat less and exercise more while implying that their weight problem is a self discipline problem.


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