The End Of Obesity

Obesity remains one of the most prevalent chronic conditions globally. Extreme obesity involves more than simply carrying a few extra pounds. It also comes with significant health complications that reduce one’s quality of life, not to mention are often life threatening. More than sixty chronic health conditions have been linked to obesity, among them heart disease, type 2 diabetes, stroke, and certain cancers. Obesity rates in the United States are also disproportionately influenced by ethnicity and geography, with Black Americans in the south experiencing some of the highest rates in the country. Studies show that this has generational effects, as well. Children born to overweight families have a substantial risk of being obese themselves.

The social determinants of obesity are influenced by several lifestyle, biological and genetic factors. The struggle that many people experiencing obesity face is losing and keeping the weight off. Previous installments of this series on overeating consistently reported that the ways in which our body responds to nutrients and stores energy is largely outside of our conscious control. At extreme levels of obesity, diet and exercise can only do so much. It is not that people lack the motivation to lose weight. Instead, any effort to reduce caloric intake or burn more calories is countered by biological mechanisms that enforce homeostasis. After starting a new diet, for example, you may experience intense hunger and a greater urge to eat than normal.

New evidence suggests that, when paired with diet and exercise, pharmaceutical interventions can enhance weight loss in those experiencing obesity. Medications for treating obesity have been on the market for decades. Often the stigma of taking these medications and the risk of adverse effects have discouraged doctors from prescribing them to patients. New understanding in how our bodies regulate weight and the discovery of novel therapeutic targets has opened the door to a new class of anti-obesity drugs that are not only more effective but also incredibly safe. To this effect, large pharmaceutical companies are pouring more money into developing new treatments than ever before. Offering similar benefits as bariatric surgery with none of the recovery time, anti-obesity drugs are projected to become a $50 billion industry in the next decade.

Since its launch in 2021, Novo Nordisk’s weight loss drug, Wegovy, set the stage for the next generation of anti-obesity drugs that target the gut’s weight-regulating mechanisms. Due to supply bottlenecks, however, Wegovy has not been able to meet consumer demand. This has increased competition among other pharmaceutical companies, such as Amgen, Pfizer, Eli Lilly, and Regeneron, to take the lead.

Now, a new drug on the scene promises to be more effective and safer than any other weight loss drug before. Manufactured by Eli Lilly, tirzepatide has a dual effect in lowering body fat and normalizing blood sugar levels. Experts anticipate that this once-weekly injection could gain FDA approval for weight loss as early as this year.

In a recent clinical study published in the New England Journal of Medicine, Jastreboff et. al reported that tirzepatide provided substantial and sustained weight loss with little to no side effects. For 72 weeks, over 2500 adults with measurably high BMIs received weekly injections of 5-, 10-, or 15-mg of tirzepatide, or a placebo drug. All the volunteers also participated in regular lifestyle counseling sessions that encouraged exercise and healthy eating.

Compared to the placebo control group, those treated with tirzepatide exhibited a greater reduction in weight in a dose dependent manner. Participants that received 15-mg weekly injections, in fact, had a 20% reduction in weight, while those in the placebo group only had an approximately 3% change. To put this into perspective, many of the other FDA-approved drugs for treating obesity have only been shown to enhance weight loss by 3.0 to 8.6%.

Jastreboff et. al found even more remarkable results when they examined the change in fat mass. Across all the groups that were treated with tirzepatide, participants lost an average of 33.9% of fat mass, compared to only 8.2% in the placebo group. This treatment regimen proves to be much more effective than diet and exercise alone.

The benefits of tirzepatide extend beyond weight loss. By the end of week seventy-two, nearly all of the participants that were prediabetic at the beginning of the trial had normal glycemic levels across all three treatment groups. This translates to a marked reduction in the risk of developing chronic kidney disease, cardiovascular disease, and fatty liver disease, among other complications, in the future. In the placebo group, only approximately 62% experienced similar benefits.

Is it safe? Yes. Overall, only 6.3% of participants experienced serious side effects, with a similar percentage reported among those in both the treatment and placebo groups. A sizable portion of these adverse events were linked to Covid-19 infections that occurred independently from the trial. Most side effects that participants experienced were mild gastrointestinal symptoms, such as constipation, diarrhea, and nausea. Of note, Jastreboff et. al found that increasing the dosage did not necessarily increase the prevalence of these side effects. The 10-mg and 15-mg groups reported adverse events at a similar rate, yet the 15-mg group exhibited significantly greater weight loss. This suggests that increasing dosage of tirzepatide to optimize its effectiveness can be well tolerated.

The duration of this 72-week trial allowed many of the participants to meet or near a weight plateau, indicating the benefits of this drug can be sustained. A group of participants from this study volunteered to be followed for a 2-year period to further evaluate the long-lasting benefits of this treatment regimen.

How does it work? Tirzepatide targets the gut’s weight regulating hormone system. Unlike Novo Nordisk’s Wegovy, tirzepatide has a two-pronged approach for detecting glucose and regulating energy levels. Previously approved by the FDA for treating type-2 diabetes, this medication was shown to improve diabetic symptoms by binding to special receptors in the gut called long-acting glucagon-like peptide-1 (GLP-1) receptors. Activating these receptors stimulates the production of insulin, which lowers blood sugar and signals to the brain to limit food intake and enhance satiety. Simultaneously in the gut, the movement of food through the stomach and intestines slows. This means that the feeling of being full occurs faster and lasts longer, preventing overeating.

Second, tirzepatide has also been shown to bind to receptors that are normally targeted by glucose-dependent insulinotropic polypeptide (GIP) hormones. In addition to facilitating the release of insulin, these nutrient-sensing receptors are also found in areas of the brain that mediate appetite and eating behavior. Activation of GIP receptors in the brain, as well as in fat tissue, regulate how calories are consumed and stored in the body. Researchers speculate that the weight loss benefits of tirzepatide comes from its ability to target both GIP and GLP-1 receptors.

Conclusion

It is not “fatphobic” for doctors to recommend weight loss drugs. Quite the opposite; it could save someone’s life. Obesity often occurs concurrently with other serious chronic complications and can also put individuals at risk of developing severe complications from infectious diseases, including Covid-19. New weight loss drugs that are hitting the market are not a substitute for diet and exercise. Rather, they optimize your body’s biology to make losing weight easier and long-lasting. As more pharmaceutical companies develop drugs that can compete with Eli Lilly’s tirzepatide, consumers can be assured that these drugs are safe and effective.