Drug companies are far better marketers than developers of new medical breakthroughs. Terms like “revolutionary”, “game-changer”, or “medical breakthrough” are used as standard practice, especially since drug companies can advertise on television. In 2024, they spent more than 5 billion dollars on television advertising. Not surprisingly, the most significant increase in TV advertising in 2024 came from GLP-1 drugs, such as Ozempic. One of the catchy advertising points is that it “reduces cardiovascular risk”.
Well, does it? Drug companies routinely talk about relative risk reduction to make their clinical trial data look impressive. However, the accurate indication of a drug’s effectiveness is the absolute risk reduction it provides to a patient. This number can be more easily understood by the average person as the Number Needed to Treat (NNT). The NNT gives you an indication of the likelihood that you will actually see a benefit if you take the drug.
However, the NNT can only be determined after several clinical trials have been published, which usually means years after the initial drug approval and the resulting marketing blitz by the drug companies, who want to maximize their return on investment in the shortest period of time. Therefore, it takes years to gain enough information to make an NNT calculation, and drug companies have no incentive to do such calculations.
The NNT is defined as one divided by the absolute difference in clinical benefits between those getting the drug versus those getting the placebo. As an example, if two percent of the people taking a hypothetical drug had a clinical benefit and one percent of the people in the placebo group had the same benefit, then the NNT for that drug would be:
NNT=1/(0.02-0.01)=100
This means only one person out of 100 who actually took the hypothetical drug as directed would see a clinical benefit. It also means that 99 out of 100 who took the hypothetical drug would not get a clinical benefit. Those aren’t very good odds, and hardly worth the name “revolutionary”. For a more detailed description of the NNT, you can go to www.theNNT.com.
So, with this explanation as background, how do GLP-1 drugs perform in preventing fatal heart attacks over four years (1)? The NNT is 1744. This means that one person out of 1744 taking the drug would be saved from a fatal heart attack. Of course, the other 1743 would have no benefits. How about preventing a non-fatal heart attack? Here, the odds are a little better; the NNT is 208. This means one person out of 208 who gets this benefit after taking the drug for years, but the other 207 taking the same drug would have no benefit.
But there are other drugs used to prevent heart attacks. These are drugs like aspirin, statins, and hypertensive drugs. So, how do GLP-1 drugs stack up against other medications?
| Drug | NNT |
| Aspirin | 361 |
| GLP-1 drugs | 208 |
| Statins | 104 |
| Hypertensive drugs | 74 |
GLP-1 drugs are more effective than aspirin, but less effective than statins and hypertensive drugs, which are a lot less expensive. But at least you lose weight with the GLP-1 drugs. While that’s true, you also have to calculate the number needed to harm (NNH) as drugs have side effects. You can calculate the NNH using a similar formula as shown below:
NNH=1/(side effects in the treated group minus the side effects in the placebo group)
Whereas the lower the NNT, the better the drug is. On the other hand, the lower the NNH, the more side effects the drug generates. Ideally, the NNT should be far lower than the NNH. Most of the side effects of GLP-1 drugs are gastrointestinal effects and nausea. For these side effects, the NNH for GLP-1 drugs is about 8. This means you are far more likely to have significant side effects (about a 12% chance) than to prevent a non-fatal heart attack (about 0.05% chance). From this perspective, GLP-1 drugs don’t look like “game-changers”.
So, if you have a cardiovascular problem, what should you do? You might consider Metabolic Engineering®. Heart disease, as well as obesity and diabetes, is strongly associated with insulin resistance. Metabolic Engineering® is an integrated dietary system designed to activate AMPK, the master regulator of metabolism (2). The most effective way to activate AMPK is by calorie restriction. Increased AMPK activity causes fat loss, reduces insulin resistance, and decreases the symptoms associated with diabetes. However, the only calorie-restriction system that generates all three benefits, plus increasing lean body mass, is the Zone diet (3, 4, 5). When you add adequate levels of omega-3 fatty acids to reduce residual chronic low-level inflammation and consume sufficient intakes of polyphenols to reduce oxidative stress that causes DNA damage to the Zone diet, now you have Metabolic Engineering® (6). The NNT of Metabolic Engineering® is very low (that’s very good) and NNH is exceptionally high (that’s great). Now that’s a game-changer.
References
1. Tang ASP, Hsu JTY, Chong SKS, et al. Glucagon-like peptide-1 receptor agonist in myocardial infarction and atherosclerotic cardiovascular disease risk reduction: A comprehensive meta-analysis of number needed to treat, efficacy and safety. Cardiovasc Diabetol. 24:285 (2025). doi: 10.1186/s12933-025-02840-3.
2. Herzig S, Shaw RJ. AMPK: Guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 19:121-135 (2018). doi: 10.1038/nrm.2017.95.
3. Stentz FB, Brewer A, Wan J, et al. Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial. BMJ Open Diabetes Res Care. 4:e000258 (2016). doi: 10.1136/bmjdrc-2016-000258.
4. Stentz FB, Mikhael A, Kineish O, Christman J, Sands C. High protein diet leads to prediabetes remission and positive changes in incretins and cardiovascular risk factors. Nutr Metab Cardiovasc Dis. 31:1227-1237 (2021). doi: 10.1016/j.numecd.2020.11.027.
5. Stentz FB, Lawson D, Tucker S, et al. Decreased cardiovascular risk factors and inflammation with remission of type 2 diabetes in adults with obesity using a high protein diet: Randomized control trial. Obes Pillars. 4:100047 (2022). doi: 10.1016/j.obpill.2022.100047.
6. Sears B, Saha AK. Dietary control of inflammation and resolution. Front Nutr. 8:709435 (2021). doi: 10.3389/fnut.2021.709435.
