Episode #10: GLP-1, A VC’s Personal Experience

Grant:

Mike, can you introduce yourself and your journey with GLP-1 drugs?

Mike:

I’m the founder and CEO of Alumni Ventures. I started in the 80’s in VC, and my whole career has been at the intersection of technology and entrepreneurship.

I think my weight journey is probably pretty similar to that of a lot of folks. I was an athlete in college, and since then, have put on a pound here, a pound there. COVID happened, I hit 60, and all of a sudden, I’m 40-50 pounds above what I should be. And meanwhile, I’ve been watching my numbers go in the wrong direction with blood sugar, metabolic issues, and heart health.

As an active investor and technologist, I was aware of and very curious about this GLP-1 technology from early on. Given the issues I described, I thought it might be the right choice for me. I actually had to bring my doctor up to speed. I had done a lot more research on the drug than he had.

After some back and forth, we jointly agreed that we were going to give it a try— as part of a holistic approach to health, which included regular exercise, discipline around sleep, etc. So, I started on Mounjaro.

Grant:

Thanks for sharing. Perhaps unique for your journey is that, as an avid technologist, you discovered this product before your doctor was actually familiar with it. And so you had to bring him along for the journey and kind of defined your own care plan. And how did things go? How did you respond?

Mike:

I was lucky to be a “super responder.” Everyone’s mileage varies on these drugs, and I found I was able to lose 50 pounds in six months on a very low dose, with no side effects. I noticed some other positive effects of the drug: my blood sugar levels were much healthier, my energy levels were more stable, and I was less distracted with “food noise” and other forms of craving behavior.

Some of these effects were flywheels for a healthier lifestyle. I feel more energized to exercise, and exercise feels easier. I don’t snore anymore, and I sleep better. My knees don’t hurt after a run or a long day on my feet. Each of these things reinforces the positive effects. In all, this has been a really profound experience for me.

I eventually tapered completely off the drug, as I had a surgery coming up, which we wanted to go into without any potential adverse effects. After being off the drug for a few weeks, I started to notice the food noise creep back into my life, and I regained a few pounds.

Grant:

Interesting. So you saw the negative rebound effects. What’s your approach toward managing those?

Mike:
People tend to think of weight and weight loss as a character issue and a discipline issue, and I think that’s really misframing it. For many people, I think chronic disease is more appropriate framing.

Some people can smoke their entire lives and not develop lung cancer. Some people eat unhealthy foods and have poor exercise habits and still remain thin. Others are very disciplined and yet bear a disproportionate load of the adverse effects. We each deal with the unique dysregulations in our bodies. And now, for this category, we have a medicine which can really treat this as the chronic condition that it is.

Culturally, this shift of mindset hasn’t happened yet. Most people still view taking GLP-1 drugs as “cheating” and ask, “why don’t you just diet or exercise more?” And I think that comes from a misunderstanding and misframing of the problem.

Fundamentally, these things are all personal. Personally, I want to be on as few drugs as I can, and I want to have a healthy lifestyle, but I also want to enjoy life a little. Studies show that alcohol is objectively bad for you, but I choose to still enjoy a drink every now and then – even if it isn’t maximizing the health vector of my life. Similarly, I make my own choices on medication and lifestyle to optimize my own definition of quality of life. Yes, I aspire to exercise and eat healthy. And I can also be on a GLP-1 drug.

So long story short, I’m getting back on Mounjaro. I’ll be taking it on a low, maintenance dose for the foreseeable future, as a way to help manage my weight on an ongoing basis.

Grant:

I would draw a parallel here with the advent of SSRIs, which are a class of drugs used to treat depression and anxiety. When these initially came out, mental health was so stigmatized that folks would say “snap out of it,” or ‘just exercise more, get more sunlight, and spend more time with friends.” And while those things may be useful, these pieces of folk advice similarly show a misunderstanding of what is actually a chronic disease for a lot of people.

When these drugs came out, they were seen as a crutch for people who didn’t have the strength to “right their own ships.” As society got onboard, the framing evolved to seeing these drugs as an effective catalyst or righting mechanism for people to get back to baseline. And the expectation was they would wean off and be in a better position to follow people’s advice on cheering up and exercising as a way to maintain their health going forward.

Now, finally, SSRIs are starting to be seen as legitimate for long-term use. So I agree with the overall trendline of destigmatization that you’re expecting to see with GLP-1s. With that said, now that we have a robust dataset of use for SSRIs, we’re starting to see that longitudinal use does result in evolving side effect profiles – and makes you more susceptible to diseases like dementia. We don’t have the same robust corpus of data for long-term GLP-1 use, so we don’t really know what the longitudinal effects might be.

How do you feel about the unknowns of long-term effects here?

Mike:

I think this is the classic risk-reward analysis. My framework here is comparing whatever the side effects and risk profile of the drug might be to the known effects of obesity. These are cancer, heart disease, diabetes, to name a few. So, I’d be weighing the potential downstream side effects of a drug which I haven’t had an adverse reaction to yet, with the very real effects of this disease.

The second thing is that we are in the early days of this class of drugs. My view is that there will be future versions of this drug that will be more targeted, with fewer side effects. So personally, I think I’ll be on Mounjaro for a few years at most before I transition to the next generation of these drugs.

This has some rough similarities with what cancer patients go through. They have a disease, and there’s a potential treatment which may come with significant side effects. It’s the risk-reward of going on the drug versus not. And then, there’s the argument that even if they can just survive another five years, there may be new treatment options available to them.

And, of course, it’s not this black and white. There’s an argument that some of the effects of the drug will allow the brain to rewire away from poor eating habits and some addictive behaviors. There is a cohort of people who will be able to keep the weight off and achieve other health without the continued support of medication. There’s another cohort which can keep it off with a low dose over a long period of time. There’s another cohort which may choose to alternate being on and off the drug. I think this is very personal, and everyone will have their own risk-reward framework.

As these drugs become more effective, and as the culture becomes more accepting, I believe more and more people will come to believe that the rewards outweigh the risks. I believe in 10 years from now, for a large swath of the human population, weight will be more of a choice than it has ever been. And that has huge implications for our society and economy — to the positive, mostly.

Grant:

You mentioned some predictions for the future, and you even cited your own experience of how your exercise habits have changed. Some people believe that after a course of GLP-1 drugs, with people feeling lighter, they’d be more likely to recreate. And others feel like as a result of this, the population will feel “hey, what’s the point of exercise? I’m already feeling good and looking good.”

The same disagreement exists with people eating out. On the one hand, people will be craving food less and eating less in terms of volume. On the other hand, they may be more proud to be seen out and about and have higher energy levels to engage in more social activity.

There’s people on both sides of each of these future debates. What are some of your predictions around food, fitness, health, and other parts of American life over the next 10-20 years, as a result of these drugs?

Mike:

In my experience, the food quality I’ve craved has gone way, way up. There’s less food noise directing me towards high food volume or high-fat, high-sugar meals. And so I can approach with a clear head, “what would I most enjoy eating right now?” I’ve found the drug doesn’t affect taste or enjoyment – so I think nicer dining experiences will be on the rise. I’ve personally experienced higher social energy levels, and feel people will have greater social confidence.

On the exercise piece, my take is that high energy will result in people exercising more – but more for the joy of movement than for the raw utility of weight loss. Activities like hiking may see a rise in popularity.

You’ll hear arguments from the other side, but my take is that the baseline will move towards more healthy, social, active people generally. I think the drug gives us one of those rare chances of transcending some of the evolutionary hardwiring which keeps us down: dopamine loops around the food scarcity mindset, specific caloric cravings, and other obsolete survival instincts. So for me, this is more about the rational brain having its day in the sun.

So, if I’m right about this thesis, how do you invest behind it?

First, I believe the peptide hormonal therapeutics technology of GLP-1 drugs has a lot of adjacent promise. We’re starting to see promising data around similar drugs treating indications as broad-ranging as Parkinson’s and sleep apnea. Beyond the horizontal implications of this therapeutic technology, we’ll, of course, continue to see vertical drug innovation in the weight management space.

The next level up is telemedicine. Prescribing the drug is one thing, but if you’ve been overweight for decades and are suddenly 50-100 pounds lighter, there is a whole set of other things you have to deal with as a human being. There are opportunities in telehealth where you really are addressing the whole person as a result of this drug. What should people eat now? How should food be prepared with family? How should people exercise? What does social and psychological adjustment look like?

I have a connection who is a plastic surgeon. He’s had a huge uptick in patient volume due to the number of GLP-1 patients who have lost a great deal of weight in their faces and now need help with excess skin or wrinkles. I hadn’t even thought of that as a downstream area of impact.

This leads to my next point. Even more exciting than these avenues is that it’s not just incumbent upon us as the VC to come up with these ideas. Our duty and privilege is to come with prepared minds when founders pitch us their own ideas, which almost always outshine ours.

Grant:

Totally. I agree with you that right now in the early stages, the value is going to be primarily captured by the therapeutics players, then the service providers around the therapeutics players, and once they become fully priced, we’re going to start to see more macro-level strategies around the downstream impacts to things like fitness, food, etc. Those are going to be the opportunities, and it’ll be up to us to spot them. And the good news is that we’re a multi-stage, multi-sector investor with the opportunity to do that.

Mike:

That’s right. Thanks for the time, Grant. Interesting conversation.

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