Why some people are more likely to get good results

• Tirzepatide is a once-weekly GIP/GLP-1 receptor agonist used for weight loss in obese adults.
• A new analysis of the SURMOUNT clinical trial finds that the drug, administered as a once-weekly injection, leads to significant weight loss.
• Across all doses and trials, women lost up to 24.6% of their body weight compared with 18.1% in men, indicating that there may be gender differences in drug response.

obesity It is the most common chronic health condition worldwide, affecting approximately 650 million adults.

Recent studies have shown that drugs that target specific hormones involved in energy balance, such as GLP-1, can help people lose weight effectively and safely.

Another hormone, GIP, also plays a role in controlling weight, and combination treatment targeting both GIP and GLP-1 receptors may be even more effective.

Tirzepatide is a new drug that acts on both the GIP and GLP-1 receptors and is already approved for the treatment of type 2 diabetes.

Early studies have shown it to be more effective at reducing weight in mice compared to treatments that target GLP-1 alone, and studies in people with type 2 diabetes have also shown promising results for weight loss.

for example, Thermomount 1 The (SM-1) trial investigated the effectiveness of tirzepatide for weight loss in non-diabetic obese or overweight people.

To further explore potential differences in how men and women respond to treatment, the researchers conducted four clinical trials:SM-1 (Up to SM-4).

According to their analysis, weekly injections Tirzepatide Substantial Weight loss For both men and women, women experienced greater weight loss.

The findings, presented at the European Association for the Study of Diabetes (EASD) Annual Meeting in Madrid (September 9-13), compared tirzepatide with a placebo in 4,677 obese adults (2,999 women and 1,678 men) over a 72-88 week period.

“This is a post-hoc subgroup data analysis from the SURMOUNT-1, SURMOUNT-2, SURMOUNT-3, and SURMOUNT-4 Phase 3 trials, which showed that tirzepatide injections (5 mg, 10 mg, 15 mg) significantly reduced body weight compared to placebo, regardless of gender, and that women experienced greater weight loss with tirzepatide compared to men.”

— Dr. Luis Emilio Garcia Pérez

In the SM-1 and SM-2 trials, randomization took place immediately after the screening period, whereas the SM-3 trial had a 12-week run-in period with intensive lifestyle modifications, and the SM-4 trial had a 36-week run-in period with open-label tripeptide treatment.

This analysis assessed weight change in participants who received at least one dose of tirzepatide (5, 10, or 15 mg) or placebo.

In this study, mixed models were used to assess differences in mean weight change over time (baseline to end of study: 72 weeks for SM-1 to SM-3 and 88 weeks for SM-4).

Logistic regression was used to assess whether male and female participants differed in achieving specific weight loss milestones, such as losing 5%, 10%, or 15% of body weight.

Across the four studies, women made up between 51% and 71% of participants.

Also, at the start of the study, women weighed less, on average, than men: in SM-1, for example, the average female participant weighed 99.8 kg, compared with 115.2 kg for men.

However, men and women had similar levels of body mass index (BMI), indicating similar levels of obesity.

With regard to weight loss, the estimated weight loss was significantly greater in people taking tirzepatide than in people taking placebo, regardless of gender.

At all doses, women experienced greater weight loss than men.

For example, women lost up to 24.6% of their body weight, while men lost up to 18.1%. This difference was statistically significant in all studies.

Looking at specific weight loss thresholds, both men and women were much more likely to achieve a 5%, 10% and 15% loss in body weight with tirzepatide compared to placebo.

However, in most studies, there were no significant differences between men and women in reaching these thresholds.

An exception was seen in the SM-3 trial, where women were more likely than men to achieve the 5% and 10% weight loss goals.

Safety results were generally similar in men and women, although women reported a higher incidence of nausea and vomiting compared to men.

“Analysis showed that weight loss occurred consistently regardless of gender, although tirzepatide was associated with greater weight loss in women than in men. The prevalence and treatment outcomes of obesity may differ in men and women as a result of physiological, sociocultural, and environmental factors.”
— Dr. Luis Emilio Garcia Pérez

However, he added that “the results of this post-mortem analysis are only hypothesis generating and should be interpreted with caution.”

“The potential mechanisms behind this finding require further study,” Dr. García-Pérez explained.

Mark A. Anton, MDThe medical director of Slimz Weightloss, who was not involved in the study, said: “This study on weight loss with tirzepatide is promising and consistent with our clinical observations.”

“The findings from this study may provide greater insight into the effectiveness of tirzepatide in different demographics and allow for more individualized treatment plans,” Anton explained.

“These findings could mean more tailored and effective weight loss solutions, increasing overall success rates and improving long-term health outcomes,” he added.

Mir B. Ali, MD“This is an interesting study comparing weight loss in men and women,” said Dr. Schneider, a board-certified bariatric surgeon and medical director of the MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California, who was not involved in the study.

“This is somewhat the opposite of what I see in surgical weight loss patients. To me, this study shows that while both men and women saw significant benefits, women may be more responsive to these drugs,” Ali added.

“These findings may help prescribers set more realistic expectations based on gender for patients seeking these medications. It would be helpful if further research was conducted in this area to consider modifying dosing based on gender.”

— Mir B. Ali, MD