When it comes to weight loss medications, new research suggests that two mechanisms of action may be better than one. In the first direct comparison of its kind, people with obesity who took tirzepatide marketed under brand names like Mounjaro and Zepbound lost significantly more weight and inches from their waist than those who used semaglutide, known as Ozempic or Wegovy.
Semaglutide is a GLP-1 receptor agonist, which mimics the hormone GLP-1 to suppress hunger. Tirzepatide, on the other hand, is a dual agonist, targeting both GLP-1 and another hormone pathway known as GIP. This dual action means tirzepatide stimulates two hormonal pathways that control appetite and metabolism, offering a more robust intervention for weight loss than semaglutide’s single-pathway approach.
Participants taking tirzepatide in the study lost approximately 20% of their body weight, compared to about 14% for those on semaglutide. The difference was even more striking among those who achieved dramatic weight loss. Of the individuals who lost 25% or more of their body weight, 32% were on tirzepatide, while only 16% were on semaglutide. This highlights tirzepatide’s stronger impact in helping patients meet ambitious weight loss goals.
The trial enrolled 751 people with obesity, dividing them evenly between the two drugs. Each participant received weekly injections over a 72-week period, with dosages adjusted to the highest level they could tolerate without severe side effects. Most participants were women in their mid-40s, primarily White, and had been living with obesity for an average of 16 years. All had previously tried and failed to lose weight through diet alone.
Beyond overall weight loss, tirzepatide users also saw a greater reduction in waist circumference. On average, participants lost 7 inches from their waistlines with tirzepatide, compared to 5 inches with semaglutide. A 2-inch difference may seem small, but in clinical terms, it is significant. Reductions in waist circumference are associated with improvements in metabolic health and a decreased risk of conditions like high blood pressure, type 2 diabetes, and heart disease.
These physical changes were matched by measurable improvements in metabolic markers. Those on tirzepatide showed better results in blood pressure, blood sugar, insulin sensitivity, and cholesterol levels. As a general rule, greater weight loss tends to lead to more pronounced improvements in these key health metrics.
Both drugs did come with side effects, primarily mild gastrointestinal issues such as nausea and diarrhea. However, these side effects led to treatment discontinuation in only a small number of participants around 6% for tirzepatide and 8% for semaglutide suggesting that most people tolerated the medications well.
While tirzepatide demonstrated superior weight loss and health outcomes in this trial, choosing the right medication depends on various factors. These include individual health profiles, doctor recommendations, and insurance coverage. It’s not just about the numbers access and affordability also play key roles in treatment decisions.
With about 150 weight loss medications currently in development, this era is rapidly shaping up to be a golden age for obesity treatment. As research continues and more drugs reach the market, patients and healthcare providers will have an expanding toolkit to combat obesity and its related health challenges.v
