• Anti-obesity medication Zepbound (tirzepatide) delivers significant weight loss even in people with multiple obesity-related medical conditions, a new study found.
  • The research challenges the concept that people with chronic health issues linked to obesity lose less weight than healthier individuals.
  • The findings suggest that tirzepatide is effective regardless of the number of obesity-associated diseases a person may have.

Obesity is known to cause or exacerbate over 200 chronic conditions. It’s commonly believed that people with multiple medical issues cannot lose as much weight as those without such problems.

In a new study, researchers wanted to find out if having more diseases linked to obesity would result in less weight loss.

The findings suggest that medical conditions associated with obesity do not affect the total weight loss achieved with the anti-obesity medication Zepbound (tirzepatide).

The research, funded by tirzepatide manufacturer Eli Lilly, was presented June 1 at ENDO 2024, the Endocrine Society’s annual meeting in Boston, MA. The research has yet to be published in a peer-reviewed scientific journal.

In this new study, researchers found that tirzepatide treatment led to significant weight loss regardless of the number of obesity-related complications patients had at the beginning of the study.

The researchers analyzed data from four different trials, which varied in design and patient characteristics but included a total of 4,726 subjects with obesity (BMI greater than 30) or overweight (BMI of at least 27) with an obesity-related medical condition. Among these, 938 subjects from one trial had type 2 diabetes (T2D).

Weight loss in the tirzepatide groups was categorized by the number of obesity-related conditions (none, one, or two or more) and compared to those who received a placebo.

As expected, older participants or those with a longer history of obesity had more obesity-related comorbidities.

Regardless of the presence of other obesity-related conditions, participants treated with tirzepatide experienced greater reductions in body weight compared to those who received a placebo.

Lead author Sriram Machineni, MD, associate professor of Medicine at the Albert Einstein College of Medicine in New York, explained the key findings to Medical News Today:

“Weight loss with Tirzepatide in patients with multiple medical issues, such as hypertension, sleep apnea, liver disease, etc., is no different from those who do not have medical issues apart from obesity.”

Mir Ali, MD, board certified bariatric surgeon and medical director of Memorial Care Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, not involved in the study, told MNT “this research confirms what we have seen in our weight loss surgery patients.”

“The weight loss is independent of the other comorbid conditions. In fact, it is the other way around, in that the weight loss leads to improvement in other comorbid conditions. Also, this study shows that these newer medications are much more effective than what we have had available to us in the past.”

— Mir Ali, MD, bariatric surgeon

Tirzepatide was approved by the Food and Drug Administration (FDA) for chronic weight management in November 2023.

Marketed under the trade name Zepbound, the medication is prescribed for chronic weight management in adults with obesity or overweight and at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol.

Administered as a once-weekly injection under the skin, tirzepatide effectively lowers blood sugar levels and promotes weight loss better than current treatments.

The most common side effects include nausea, diarrhea, and vomiting, which tend to diminish over time.

Tirzepatide belongs to a new class of diabetes medications as a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. GLP-1 and GIP are incretin hormones released by the intestines when we eat.

Incretins stimulate insulin secretion from the pancreas’ beta cells. GLP-1 enhances insulin release from the pancreas and reduces glucagon levels, a hormone that prevents excessive drops in blood sugar. It also increases the number and size of beta cells, promotes a feeling of fullness by delaying stomach emptying and controls appetite through the brain.

Similarly, GIP boosts insulin release, enhances beta cell production, and reduces beta cell destruction. GIP also decreases fat accumulation, promotes bone formation, increases glucagon production, and reduces stomach acid secretion.

People with type 2 diabetes have a weaker response to incretin hormones. Tirzepatide addresses this issue by activating both GLP-1 and GIP receptors in the body.

The findings from this new study are promising for people with multiple health conditions, but GLP-1 drugs like Zepbound are already in short supply.

Machineni pointed out that “tirzepatide which is now approved and available for the treatment of obesity is beneficial to patients regardless of the number of complications they may have already developed from it.”

Ali agreed, adding “there are a wider range of patients that may benefit from these medications. Unfortunately, that may mean an increasing shortage of these medications as we are seeing now.”

Jared L. Ross, DO, assistant professor in emergency medicine at the University of Missouri, also not involved in the research, highlighted that “the results of this study have to be taken in context as it was funded by Eli Lilly the manufacturer of tirzepatide.”

“Additionally, the lead author has received significant financial support from the pharmaceutical company over the last several years as publicly available in the Open Payments Database as a result of the Sunshine Act,” Ross added. “That aside, the findings are not unexpected.”

“A vast majority of patients with obesity likely have these comorbid complications, and whether or not they are aware of those conditions likely depends more on their access to primary care and not their underlying health conditions,” Ross noted.

“Tirzepatide is approved to treat both type 2 diabetes as well as obesity, likely via the same mechanism underlying metabolic syndrome. There is no reason to suspect that a medication that targets a mechanism that likely underlies both comorbid diseases would have less efficacy in a patient with both disease processes. Additionally, the findings of the study are somewhat limited by the fact that obesity-related complications were determined by self-reporting by participants.”

— Jared L. Ross, DO, professor of emergency medicine

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