We are living in exciting times. Finally, we are seeing the emerging new class of extremely safe and highly effective weight-loss drugs. Unlike previous drugs that could barely help lose a few pounds on prolonged use, this new class of drugs, to which tirzepatide belongs, can help shed significant body weight. Moreover, these new class of drugs have numerous benefits for endocrinal health. These drugs are well-tolerated and good for prolonged use. So, finally, there are drugs that can help meet body weight targets.
In the last few decades, researchers have started looking at obesity very differently. Obesity is no longer viewed as merely excessive weight due to certain food habits. Instead, doctors see obesity as a disease that must be actively treated. This explains why so many new treatments have started emerging.
Obesity is a complex health issue affecting 70% of people living in the US. The US is the fattest nation in the world, with more than 40% of people obese and another 30% overweight. Obesity is not just about overweight. It is also about mental health issues, brain disorders, joint pains, increased heart disease risk, diabetes risk, and more.
In the last few decades, researchers have started to realize how most non-infectious diseases are interrelated. They have started seeing a relationship between diabetes, heart disease, kidney disease, dementia, and other conditions. The risk of most of these conditions increases by several times due to obesity. Hence, by countering obesity, it is possible to reduce the risk of numerous health issues significantly.
Furthermore, it is vital to understand that obesity does not only kill. It causes much disability. Those with obesity are more likely to develop arthritis, live with low self-esteem, and develop depression and various mental health issues.
Needless to say, exercise and dietary changes are two of the best ways of managing obesity. After all, excessive calorie consumption and low expenditure are the root causes of obesity. However, these measures do not work for many. This is because many people living with obesity cannot stop eating food. Exercise also fails to help in most cases, as burning calories is a slow and painful process.
Drugs like tirzepatide can completely transform weight loss efforts. These drugs help in many ways. They reduce appetite, promote burning calories, improve insulin sensitivity, increase energy levels, positively impact brain health, prevent mood issues, and minimize the risk of binge eating. Consequently, just a single weekly subcutaneous injection of tirzepatide can transform health, promoting weight loss, unlike any other drug.
How Tirzepatide Works?
This is a new kid on the block in every way. It was approved for managing diabetes just in 2022, under the brand name of Mounjaro.(1)
Since its approval, researchers have started testing it for managing obesity. From their experience with semaglutide, they knew that this class of drugs is excellent for managing obesity or for weight loss. Hence, this time, the US FDA was pretty quick to approve it for obesity treatment or as a weight loss drug under the name of Zepbound.(2)
Before we further see how tirzepatide works, it is good to know that Mounjaro and Zepbound are both brand names of the drugs containing tirzepatide. Thus, these three names can be used interchangeably.
Tirzepatide is a drug belonging to an entirely new class of medications called GLP-1 and GIP agonists. Of course, it shares many traits with already existing one of the potent anti-obesity drugs, that is, semaglutide/Ozempic/Wegovy.
However, unlike semaglutide, it has a broader action, making it more potent. This is because it affects two incretin hormones, unlike semaglutide, which affects just one. So, let’s explore how it works and what makes it such a potent weight-loss medication.
It has taken almost 100 years for science to develop drugs that can effectively modulate the activity of gut hormones called incretins. Researchers first identified incretins in 1929, when they found that gut extracts have some hormone that can influence insulin production, and they named this hormone incretin (INtestine seCRETtion Insulin).(3)
Although science knew that the human gut secreted hormones that can influence insulin secretion and various body functions, but it took many more years to describe these hormones precisely. They soon realized that there are two chemically related and slightly different incretins: gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Unlike semaglutide, which can only boost GLP-1 production, tirzepatide is both GIP and GLP-1 agonist. Hence, it can provide better cover.
These hormones can be seen as metabolic regulators. They have a wide variety of functions and do not just increase insulin production. The human gut starts secreting these hormones in response to food intake, especially in response to foods rich in carbs. These hormones send signals to the pancreas, brain, and other body parts, thus playing a vital role in metabolic regulation.
There are many similarities between GIP and GLP-1 hormones but with some significant differences.
Thus, both GLP-1 and GIP receptor agonists slow gastric emptying, boosting insulin production and beta-cell proliferation in the pancreas. This is the primary way in which tirzepatide works. Slow down in gastric movement and improved glucose metabolism results in weight loss.
Additionally, GLP-1 agonists also promote weight loss by reducing appetite. Tirzepatide boosts heart health, improves memory, stimulates nerve growth, and more. Unlike semaglutide, it also enhances bone formation, and thus, it is suitable for bone health. GIP receptors also promote the accumulation of excessive fats in fat tissues, helping reduce bad cholesterol levels in the blood.
So, as one can see, the additional GIP agonist effect of tirzepatide results in a much more potent action; this naturally means better blood glucose control and more significant weight loss.(4)
What Does the Science Say?
Tirzepatide is not a US FDA-approved medication for managing obesity. It means there is sound scientific evidence favoring its prolonged use for weight loss. This means that its benefits outnumber the risks. This also means that the drug is now proven beyond doubt to be effective for weight loss. When it comes to science, there is clear evidence that tirzepatide is even more effective than blockbuster semaglutide/Ozempic.
Soon after its approval for managing diabetes in 2022, researchers started testing tirzepatide for managing obesity in non-diabetic patients. From their early experience with semaglutide, they knew that drugs belonging to this class are safe and effective even in non-diabetics. This is because drugs improving incretin sensitivity and function normalize insulin secretion and do not cause excessive insulin production. Thus, they boost insulin production in those living with diabetes but have minimal impact on insulin levels in those living without diabetes. In obese patients, these drugs can help reverse pre-diabetes, which is a common issue, and thus help prevent diabetes in the future.
To get clinical approval, the producer of this drug carried out one of the most extensive studies, named the SURMOUNT-1 clinical trial, and they had many interesting findings.(5)
In the study, researchers tested tirzepatide in 2539 adults with a BMI above 30 or those with a BMI of 27 with some excessive weight-related complications. The mean weight of participants was above 100 kg, and the BMI of 38. Thus, most of the participants were quite obese. The study was continued for 72 weeks or one and a half years.
The study used 5, 10, and 15 mg of weekly tirzepatide dosage. Researchers found that at the end of the study, those given a 5 mg drug could lose 15% of their body weight, those with a 10 mg dose could lose 19.5%, and those given 15 mg could reduce body weight by 20.9%. So, the study demonstrated that all dosages were quite effective. However, perhaps 15 mg is the optimal dosage, and going beyond it does not necessarily result in more significant benefits. Here, it is worth noticing that, in contrast, the placebo group could only reduce body weight by 3%.(5)
Another thing is worth understanding: ~20% is an average weight loss for all participants in the 10 to 15 mg group. However, those who made significant efforts also had significantly greater weight loss. In simple words, one can even expect 30% or more weight loss by following lifestyle recommendations. This means that most users, even if they are grossly obese, can expect to have normal body weight after one and a half years of treatment. These findings are incredible in every aspect.
Further, one should not forget that tirzepatide is not just good for weight loss. Such weight loss also means considerably improved metabolic health. Those using tirzepatide can especially expect significantly enhanced energy levels and improved heart health. If one is able to sustain the weight loss, this may reduce the risk of health issues like heart disease and stroke by several times.
Of course, tirzepatide is also good for weight loss in those living with diabetes. In diabetes, it has a double benefit of diabetes management and weight loss. It is quite possible that many of those living with diabetes might be able to reverse their condition on prolonged tirzepatide therapy. After all, studies show that weight loss can be really helpful in managing and even reversing diabetes.(6) When it comes to comparing it with semaglutide, studies confirm that it is not inferior to semaglutide and is better in many ways.
Comparison of this drug with a blockbuster weight loss drug semaglutide is natural. It is relatively easy to understand why tirzepatide is even better. It influences both incretins, unlike semaglutide. Hence, it has a more potent effect on gastric emptying, appetite, brain function, and pancreatic health.
However, in practice, it is also worth noticing that tirzepatide is just slightly better. It means that both drugs are good for weight loss. The decision to use a particular drug must be taken by consulting a specialist.
Further, remember that tirzepatide is more potent but has a greater impact on gastric function, resulting in more significant side effects. These drugs cause gastric distress in most patients, and tirzepatide is even more likely to cause issues like nausea, vomiting, and diarrhea.(6)
However, there is also good news. Quite like semaglutide, people get used to the drug, and they develop resistance to side effects. They become tolerant to these side effects after a few weeks of use. These gastrointestinal side effects are transient and rarely the cause for discontinuation of the therapy.
Gastrointestinal side effects mean that doctors start tirzepatide at a very low dose and they gradually increase its dosage every four weeks. Hence, patients can slowly become used to the drug. Only a few users might have severe gastrointestinal issues and may need to discontinue its use.
Tirzepatide Safety
Now, let us discuss its safety as people have to use it for a long time. Most would need to use it for a year or more. As already said, the most significant issue with the drug is gastrointestinal issues like diarrhea and nausea. However, the risk of these issues can be minimized by increasing its dosage gradually, as these side effects are transient.
Fortunately, the drug does not cause severe side effects. Severe issues are quite rare. Thus, the drug is safe for the liver and rarely affects the kidneys. Some may experience kidney issues due to dehydration. However, again, such problems are short-lived and reversible. Very few patients might develop skin allergies.
Tirzepatide may cause pancreatitis in rare cases; hence, it must be used under medical supervision. There are also concerns that it may increase the risk of thyroid cancer. However, keep in mind that these are findings from animal studies, and there is no proof that these issues occur in humans. Nevertheless, the drug must be used with caution in those with a family history of thyroid issues.(1)
One of the concerns with tirzepatide use is that many people start regaining weight on its discontinuation. This is more likely to occur in those who rely solely on the drug and fail to make any lifestyle changes. To prevent weight regain, it is essential that one should also start making lifestyle changes from day one of the therapy. So, start making dietary changes and exercising. Tirzepatide will help you succeed in your efforts.
Interestingly, researchers are now also exploring using tirzepatide to prevent weight regain. Studies show that it is good for preventing weight regain.(7)
However, there is a need for more research into the topic. It must be remembered that the drug was approved for weight loss in non-diabetes in just 2023. Therefore, it is pretty likely that we might see more studies regarding its safe use in the future. It is quite likely that such drugs may also find broader use in managing various other metabolic health issues.
Future studies will shed greater light on its role in reducing the risk of heart attack, stroke, and even dementia. However, it is pretty safe to believe that it can reduce the risk of a range of non-infectious diseases. These benefits are both due to weight loss and better metabolic health.
The Bottom Line
Tirzepatide is one of the most potent drugs ever approved for managing obesity. What is good about semaglutide and tirzepatide is that these drugs are safe for prolonged use. Unlike previous-generation weight loss drugs, tirzepatide can help achieve significant weight loss in a year or year and a half. Most people who would combine tirzepatide with lifestyle intervention can expect to have an absolutely healthy weight by using these drugs.
Of course, lifestyle interventions are strongly recommended. Although these drugs are wonderful and they work even in the absence of any lifestyle interventions, if one does not carry out lifestyle intervention, then there are some real chances that one may regain weight on discontinuing the drug therapy.
Yet, another good thing about tirzepatide is its benefits for metabolic health. It is not just a weight loss drug. It is quite good for changing body composition, altering appetite, reducing bad cholesterol, and boosting heart health.
Further, one must not forget that tirzepatide is also good for brain and nerve health. This means that it may enhance memory and mood and reduce the risk of emotional disorders. At present, there are no studies to show how good is tirzepatide for brain health. However, future clinical trials would likely focus on the additional health benefits of this fantastic drug.
To sum up, tirzepatide therapy can be life-changing for those living with obesity. For the first time, medications provide hope of significant weight loss without surgical intervention. Another thing that it incredible about this drug is that one requires just one sub-cutaneous injection a week. This can significantly improve treatment compliance. There is no need to take daily medications. The subcutaneous route is among the safest routes and does not cause local pain or inflammation. So, if your BMI is above 30, or even if you are overweight (with a BMI above 27) and have some other metabolic health issues, then this drug is a perfect remedy for you.
References
- Farzam K, Patel P. Tirzepatide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Mar 22]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK585056/
- Abbasi J. FDA Green-Lights Tirzepatide, Marketed as Zepbound, for Chronic Weight Management. JAMA. 2023 Dec 12;330(22):2143–4.
- Seino Y, Fukushima M, Yabe D. GIP and GLP‐1, the two incretin hormones: Similarities and differences. J of Diabetes Invest. 2010 Feb;1(1–2):8–23.
- Chavda VP, Ajabiya J, Teli D, Bojarska J, Apostolopoulos V. Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review. Molecules. 2022 Jul 5;27(13):4315.
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022 Jul 21;387(3):205–16.
- Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine. 2021 Aug 5;385(6):503–15.
- Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024 Jan 2;331(1):38–48.
