Topic / Health / Implications
Part 2.2: Health Implications
Obesity
Over 40% of American adults are obese, and rates have risen so dramatically around the world that obesity has been called a global epidemic.
Obesity is a root cause of type 2 diabetes, cardiovascular disease, cancer, cognitive decline, joint degeneration, mental illness, physical disability, and more. So it is not much of an exaggeration to say that GLP-1s are “miracle drugs”, for the simple fact that they are the first extremely effective and safe pharmacological treatment for obesity – and thus for all of its many downstream diseases and health problems as well.
Today, GLP-1s are the most expensive and least effective they will ever be. Safety, efficacy, and cost of GLP-1s will only continue to improve in the future. And when they are combined with other safe and effective medications as HOTs, the overall health benefits will be transformative. As a result, global demand among adults for HOTs will be staggering – far greater than any other medicine in history.
Type 2 Diabetes
- Affects over 34 million Americans and with an annual direct medical cost burden of over $305 billion.
- GLP-1s are already 80-90% effective at prevention.
- GLP-1s are already 50-60% effective at treatment for those who already have type 2 diabetes.
- The mechanisms are straightforward: reduced body fat decreases insulin resistance; reduced sugar consumption improves insulin sensitivity and blood sugar stability; GLP-1s directly enhance insulin secretion and sensitivity.
Cardiovascular (Heart) Disease
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Affects nearly half of American adults, over 125 million people, and with an annual direct medical cost burden of over $415 billion.
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GLP-1 users already see a 20% reduction in major adverse cardiovascular events.
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GLP-1 users already see a 40% reduction in heart failure progression.
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Other cardiovascular benefits from weight loss include blood pressure reduction (i.e. prevention and treatment of hypertension), improved lipid profiles, decreased systemic inflammation driving atherosclerosis, and overall reduction of cardiovascular mortality and morbidity.
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Benefits start to emerge within weeks of treatment.
Cancer
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Roughly 40% of all cancer diagnoses in the United States are obesity-linked, and obesity is recognized as a driver of at least 13 types of cancer, including breast, colon, kidney, and pancreatic. These obesity-linked cancers carry an annual direct medical cost burden of over $35 billion.
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GLP-1s have already been shown to reduce cancer risk, and their impacts on cancer rates should at least match any obesity rate reductions driven by HOT use (and possibly exceed them, through other mechanisms like systemic inflammation reduction).
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GLP-1s may indirectly reduce cancer risks associated with alcohol, smoking, and other substance use and addiction.
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There are over 715,000 obesity-linked cancer cases each year in the United States. Of these, about 495,000 affect women, and about 220,000 affect men.
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More than 90% of obesity-linked cancers affect people aged 50 or older.
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Excess body fat increases cancer risk via chronic inflammation, elevated insulin levels, and hormonal disruption – all of which are improved by GLP-1s.
Osteoarthritis and Joint Disease
- Affects tens of millions of Americans, at an annual direct medical cost of over $140 billion.
- GLP-1s have already shown benefits in early research data. The STEP 9 study showed striking results of for patients taking GLP-1s (semaglutide), who reported pain reduction, functional gains, and a “cure” effect (i.e. relief was so profound that some participants no longer met the clinical criteria for joint disease by the end of the study).
- Obesity is a primary driver of knee and hip degeneration, both because excess weight causes additional force on the joints and because obesity causes systemic inflammation that leads to joint deterioration.
- Osteoarthritis and joint disease limit mobility and physical activity, creating a reinforcing feedback loop with obesity that traps millions in ill-health.
- Approximately 1.5 million joint replacement surgeries are performed annually in the United States.
Obstructive Sleep Apnea
- Affects tens of millions of Americans, with reputable sources in the peer-reviewed literature claiming annual direct medical costs as high as $95 billion.
- GLP-1s have show over 50% reduction in apnea events for GLP-1 users according to recent studies, with over 40% achieving complete disease resolution.
- Obstructive sleep apnea represents the overwhelming majority of sleep disorders, with almost 6 million Americans officially diagnosed. But, the true number is likely closer to 30 million because 80% or more of cases go undiagnosed.
- Fatigue from inadequate sleep contributes directly to motor vehicle accidents and workplace accidents, which pose enormous additional social and economic costs.
- Obesity is the primary driver of obstructive sleep apnea, and so the reduction of fat around the upper airway reduces or eliminates obstruction by fat deposits that contribute to the disease.
- The standard treatment of wearing a CPAP machine during sleep is effective, but poorly tolerated, with almost half of patients stopping use of their devices within one year.
Alzheimer’s Disease and other Dementias
- Affects over 7 million Americans, with total medical and long-term care costs of over $380 billion annually.
- Alzheimer’s disease is estimated to account for 60-80% of dementias.
- Early animal studies suggested GLP-1s might prevent dementia and/or slow its progression, but the EVOKE trial showed disappointing results, finding no such benefit in humans.
- Obesity has been linked to non-Alzheimer’s dementias, and may accelerate decline in Alzheimer’s patients. Possible mechanisms of action include high blood pressure, vascular damage, metabolic stress, and amyloid buildup.
- This is an area where the science is still evolving, but it is likely that a large reduction in obesity rates would offer some benefits in terms of preventing and/or slowing dementias.
Anxiety and Depression
- Affects tens of millions of Americans, with annual direct medical costs of roughly $44 billion and $31 billion respectively.
- When additional knock-on medical costs of anxiety and depression are included (such as increased ER visits, increased medications for co-morbidities, and so on) the total annual medical costs balloon to hundreds of billions of dollars.
- The majority of HOTs users report improvements in mental health. This is an unsurprising result of improved healthfulness and generally “looking and feeling better”.
- Some users of GLP-1s report anhedonia (reduced ability to experience pleasure), likely related to the same dopamine pathway modulation that reduces food cravings, and possibly dose-dependent (i.e. more likely to occur at high doses, less likely to occur at low/maintenance doses).
- Some users of GLP-1s report negative/difficult experiences from rapid physical transformation (e.g. from sagging skin and increased wrinkle visibility, and from separation of aspects of personal identity that were previously tied to obesity).
Addictive Behavior and Substance Use
- Approximately 28 million Americans struggle with alcohol abuse or addiction. The top 10% of drinkers consume 60% of all alcohol sold. Alcohol consumption and obesity also contribute to one another.
- Collectively, substance use and addiction affects over 50 million Americans.
- GLP-1 users report remarkable benefits in reducing alcohol, tobacco, opioids, and other addictive substances. Users also report a reduction in other addictive and compulsive behaviors, including gambling and even social media use (“doom-scrolling”).
- Alcohol use and addiction accounts for roughly $3.5 billion in annual direct medical spending. (This excludes co-morbidity, such as liver disease caused by alcoholism).
- Tobacco use and addiction accounts for about $1 billion in annual direct medical spending. (This is mostly for cessation treatment, and excludes co-morbidities such as lung cancer caused by smoking).
- Other substance use and addiction accounts for about $3.5 billion in annual direct medical spending as well. Opioid use and addiction, for example, accounts for about $2 billion annual direct medical spending.
- Alcohol contributes to larger healthcare costs through co-morbidities, with attributed annual costs of over $30 billion.
- Tobacco contributes to larger healthcare costs through co-morbidities, with attributed annual costs of over $225 billion.
- Opioids contribute to larger healthcare costs through co-morbidities, with attributed annual costs of over $95 billion.
- The science around GLP-1s and addiction is still evolving, but because GLP-1 drugs modulate dopamine signaling in the brain's reward pathways, it is not surprising that they might reduce the hedonic value of addictive substances and activities.
Late-Life Morbidity
- More than 20% of all healthcare spending goes toward elderly patients in the last years of life, with direct medical spending of over $1 trillion annually.
- Obesity combined with sarcopenia (age-related muscle loss) and frailty are key drivers of late-life morbidity.
- By treating obesity (via fat loss) and frailty (via muscle gain), the use of HOTs will reduce years of disability and morbidity, while extending healthspan and years of functional independence.
Life Expectancy
- Life expectancy plateaued in the United States after 2014 up until the COVID-19 pandemic (which distorted the signal). This occurred despite improvements in medical technologies and treatments for many cancers and other age-related diseases. Some of this plateau is ultimately attributed to rising obesity rates.
- The science is still evolving, but use of HOTs in adulthood to prevent obesity and frailty would very likely extend lifespan by several years, other things being equal.
