Absolute vs. Relative Risk in drug trials

Investment Analysis Clubs Macro Economic Trends and Risks
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GLP-1 drugs (semaglutide), like Ozempic and Wegovy, have been potential blockbusters for the manufacturer, Novo Nordisk, since their approval for weight loss in addition to diabetes. A rumor that semaglutide can damage vision can undermine the demand for this drug. That is an important question for patient as well as corporate well-being.

Drugs are approved by a clinical trial process which has limited participants and duration. Side effects can appear once the drug is used by a large population of patients for a long time.

Does semaglutide really contribute to vision loss?

…

In this most recent study, researchers conducted a systematic review of 78 clinical trials involving semaglutide use and ocular issues — including NAION, diabetic retinopathy, and eye disorders — encompassing more than 73,000 study participants….

Upon analysis, researchers found that semaglutide use was not associated with an increased risk for diabetic retinopathy or eye disorders. And although they did find a correlation between semaglutide use and NAION, scientists believe the evidence currently available is not enough to establish a definitive conclusion and more studies are needed….

“[This study] reported in the control population that it was about 0.02% of the patients (with NAION) [that is the absolute risk], and in the treated group, the ones that were taking the GLP-1 medications, it went up to 0.04%,” he explained. “So you could kind of sensationalize it and say, look, it doubled the risk for the patients to take the medication. [That is the relative risk.] But again, 0.02 to 0.04 is such a small amount that the overall risk is still very low.”… [end quote]

Nonarteritic anterior ischemic optic neuropathy (NAION) is an eye disorder that is rare. Would a doctor decide to avoid using semaglutide if the relative risk is doubled?

This question of absolute vs. relative risk is important to understand with many drugs, including cancer chemotherapy. Should a cancer patient take a chemo drug and suffer side effects if it reduces the recurrence rate by 50% [relative risk]? What if the control group has a recurrence rate of 20% and the treated group has a recurrence rate of 10% [so the absolute change in risk is 10%]?

Wendy

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I’m not really due an opinion as it’s not a field I’m really familiar with, and I didn’t read the primary document (link in the article) as the statistical analysis was so far above my pay grade it’d be obvious I was pretending. However, I did read the introduction etc and scrolled down to the Limitations. That section looked to my eyes like a list of reasons why the authors shouldn’t even have bothered with the data mine. Apparently, they didn’t even use an ICD code for NAION …. because there isn’t one.

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Budget BUSTERS for Medicare/Medicaid?

The Captain

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I agree with the authors. I would paraphrase that the exercise is too murky. Further study is needed.

The eye opener on these boards was discussing how severely ill some obese people are who need these drugs. Under extreme conditions, there is little choice.

I am on a chocolate diet these days. After the first day yesterday, I weighed myself and had lost significant weight.

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Yes, absolutely. Especially since obesity has been defined as a disease so medical treatment should be covered.

Wendy

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Nothing nearly budget busting about merely expensive drugs in comparison to the insanely bloated Congressionally mandated medical “care”/insurance racket.

Not Even Close.

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I spent one summer during medical school working in the R&D department of a pharmaceutical research lab. Primarily just double checking data and writing up initial research parameters. The researcher I worked under was looking at antidepressants, nothing at the time beat the old “gold standard”, it just nibbled on the edges of side effects.

The biggest take home from the experience, you don’t know what a drug will do until it is released into the wild. Studies are set up for patients to usually only have that disease that is being looked at. No way to take into account someone having 3 different diseases nor the multitude of drug interactions from the 20 drugs that could be used for each disease.

Then you have some drugs that work when others won’t but have horrible side effects. Amiodarone is a classic. Works great for cardiac arrhythmias but is horrible for lung damaging side effects. Had one attending call it the “Devil’s Choice”, do you die from heart problems or lung problems.

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Funny you should mention amiodarone. I took that for 3 days before my open heart surgery in November 2024 because the cardiologist said it reduced the mortality by a significant amount.

After the surgery I had a pleural effusion that reduced my functional lung capacity to 500 cc. I was on oxygen 24/7 for 9 days. I thought it was because I gained 12 pounds of fluid during the surgery. Could the amiodarone have had anything to do with my lung problem?

Wendy

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Maybe. It depends upon how much the effects of obesity cost the government.

DB2

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It all adds up. Just because something is worse does not make the bad good.

From my point of view, American socialist medicine, partly an outgrowth of corporate payroll employee benefits, is a wasteful mess.

Decades ago, instead of high pay, corporations relied on better employee benefits. in the 1960s IBM gave the option to buy IBM stock at a discount, paid for medical bills, and matched savings up to a point. The medical part might have been covered by insurance instead of self insured. I liked this system.

As corporations competed for workers employee benefits grew. When the government took over some of these plans they exploded for a very simple reason, the plans were not paid for by government bureaucrats but by the infinite pool of taxes paid by people who had no control over the system. A Spanish economist commented that a similar situation (panem et circum - bread and circus) was responsible for the fall of Rome.

But it’s worse, it was government food guidelines that prompted the obesity epidemic that led to a large number of illnesses. I fell for the fat is bad guideline. Some 40 years ago, a doctor married to a cousin of mine, told me that when he had MediCare patient he treated them for free, the bureaucracy to collect from the government was just too complicated to be worth doing. This was not altruism, it was economics. the high cost of bureaucracy.

Add in the cost of treating for free millions of illegal … Bust Alley!

The Captain

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[quote=“captainccs, post:3, topic:120840”]

Budget BUSTERS for Medicare/Medicaid?

The Captain

[/quote]

A few things to remember…..or be aware of if you weren’t in the first place

“FDA approval” doesn’t mean automatic Medicare or Medicaid coverage. Currently it seems that neither organisation does “cover” GLP-1 inhibitors for weight loss (I’m sure exceptions apply)

Additionally, Medicare….that’s “traditional” Medicare, not MA plans….doesn’t actually part with a dime for drug reimbursement outside of a medical facility. Should approval actually be extended to weight loss in the absence of the usual biomarkers used to determine T2D (which, of course, is absolutely not the same as metabolically healthy), it will be the insurance carrier chosen for Plan D coverage which will be taking the hit (i.e. passing on the cost to everyone enrolled)

Also, not every country provides its citizenry with their medical care via the same reimbursement structure as the US….and most have fairly strict controls on the price they will pay for any drug that’s included in their formulary/pharmacopeia (or whatever it’s called…..I’m only familiar with US and UK terminology.) The pharmacology, though, is the same worldwide…..my intervention cardiologist mentioned interesting data coming from some European studies showing that GLP-1 agonists are showing signs of being cardioprotective, not only in those without T2D but also in the non lardy population

I predict that GLP-1 agonists will soon rival statins as the drugs that folk are most likely to show their biases with.

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What’s that called?
APOB?
Appearance?
Apostate?
Appearance?
Apolonius?
Apolo something?
Memory fails me.

The Captain

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A study out of the University of Chicago found lots of benefits but at a price.

Drawing on nationally representative U.S. population data, the researchers used advanced simulation models to project the long-term health effects of four leading GLP-1 medications. The analysis predicted that GLP-1 drugs could prevent thousands of cases of diabetes and cardiovascular disease and add months of high-quality life to patient lifetimes on average. But those benefits come at a price: roughly $700-800 per month in the US…

That threshold is typically defined as less than $100,000 per quality-adjusted life year (QALY) — a standard tool health economists use to compare the value of medical treatments. According to the study, tirzepatide would need a 30% price reduction to meet that mark…

In the news this week is a new self-pay program for tirzepatide (Mounjaro/Zepbound) which Lilly will offer for $500/month.

$500/$750 = 0.67, a 33% price reduction.

DB2

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Maybe savings for both. Diabetes is often cited as the most or second most expensive (behind heart decease) ailment to treat by Medicare and Medicaid - and both are heavily correlated to obesity.

In 2017, complications from diabetes cost over $37 billion among Medicare beneficiaries

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As I understand it, obesity is visible but not the cause of all the related ailments. The common cause is insulin resistance, caused by excess insulin, caused by excessive carbohydrate (sugars/starches) consumption.

Choices:

  1. Treat the symptom with medication
  2. Reduce carbohydrate consumption

Choice TWO is bad for both the AgroIndustrial Food Complex and the Medical/Drug Industrial Complexes.

Humanity needs a grassroots nutrition revolution. I’m doing my bit.

The Captain

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@Hawkwin

Denny is partially right…

The common finding with obesity related T2D is insulin resistance. A complex syndrome that’s caused by a chronic excess of rations….protein and fat as well as carbohydrates…..and leads to an eventual excess of circulating insulin as a “normal” response by the pancreas to overcome the issue. This cascade of events begins to happen years…..decades, even…..in advance of the obvious signs of pathology that are measured in the metabolic panel during an annual physical. Yes…..even before that fasting blood glucose and A1c begin to rise to the arbitrary levels that give a “diagnosis” of pre-diabetes.

Since IR has developed the rep of the Canary in the Coalmine with metabolic dysfunction, just over 3 years ago……when I decided to quiet those little warning alarms, and satisfy myself that my PCPs had been correct in that my excellent lifestyle choices really were more than adequate to compensate for my “mildly elevated LDL-C” …..along with the addition of more advanced lipid testing (no extra effort over and above the Usual Suspects) and a CAC scan, I requested a circulating insulin test. Just in case. Well, my HOMA-IR showed me nicely insulin sensitive…..so no problem there. The rest…..well, I’ve written about that many times.

It’s a complex issue with no simple solutions….or even an easy way to measure that earliest departure from healthy homeostasis (NAFLD/MAFLD has been observed in the under 5s…..so maybe in utero given the right conditions)

The biomarkers are available to readily identify when someone is on the trajectory for T2D long before it’s obvious that medications are necessary….together with the options to do something about the situation.

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Americans need a swat on their collective behinds by a strict but caring parent.

IMO, obesity is not a disease. I mean, it is obviously not a disease and is only defined as one because of social pressure. It is a lifestyle choice as evidenced by the many countries with much lower obesity rates and the several on this board who have escaped obesity by lifestyle choices.

I find it depressing that so many Americans would rather take a drug for their entire life and have others help pay for it than suck it up and change their lifestyle to be healthy. Not sure when the majority of Americans decided to become parasites, but it is not a good look.

Fact is that most obese Americans today had ancestors in the WWII generation who where not overweight. Most can’t blame bad genes. They should blame bad choices.

Given this perspective, I believe if you want to use glp-1 to lose weight, pay for it yourself.

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And if they don’t pay for it themselves, are you going to deny them Medicare for T2 diabetes?

As a former libertarian, I am ALL about individual responsibility but as a humanitarian, I am not going to deny someone healthcare because they made poor decisions in life.

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Using similar reasoning, would you deny smokers insurance coverage for lung cancer treatment?

Wendy

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Unhealthy people are a drain on the economy. At the family economic level as well as local community level.

A big enough population of people (Boomer generation, Fat people, Alzheimer’s etc) affect the macro economy.

Society pays for health care in order to protect itself as much as (or more than) to protect the individual.

:thinking:

ralph

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