Dr. Santiago Tofé, an endocrinologist at Juaneda Hospitals, is conducting research on the cardiovascular safety of two molecules with weight-loss effects. Medications like Mounjaro, already on the market, and retatrutide (still without a commercial name) show significant effects in insulin control for diabetics and weight reduction in obese patients. Besides combating diabetes and obesity, they hold potential for improving cardiovascular risk.

Dr. Tofé is leading two long-term studies at this private healthcare facility to evaluate the ability of these two molecules to reduce cardiovascular events in high-risk patients.

“One of these studies began a year and a half ago,” explains Dr. Tofé, “and is expected to last four to five years. The second study started two months ago and is expected to last two to three years. The first study is on a molecule whose drug became available in Spain at the end of last July.”

The first medication is Mounjaro, whose active ingredient is tirzepatide. “This drug has garnered significant media attention due to its potency in promoting weight loss among overweight or obese individuals, whether they are diabetic or not,” notes Dr. Tofé.

The second medication under investigation is retatrutide, a molecule that represents an innovation over Mounjaro. It is still in the experimental phase and has no commercial name yet, as it is not marketed in Spain or any other country. The trial is part of its clinical development prior to distribution.”

Both medications are “agonists of incretin receptor pathways, which are hormonal pathways in all humans that regulate energy metabolism, including critical roles in managing blood sugar levels and neural pathways related to appetite and satiety,” explains Dr. Tofé.

“What has been observed with these drugs is that, in addition to regulating blood sugar levels in patients with elevated levels, they induce a strong and lasting sensation of satiety, causing patients to eat less and lose weight,” he adds.

These active ingredients are innovations over previous molecules with similar effects developed earlier. Clinical trials indicate that these newer molecules are increasingly effective in normalizing blood sugar levels and achieving substantial weight loss.

“When comparing clinical trial data for these molecules with those of earlier ones, the weight loss is more significant, as is their ability to regulate blood sugar in diabetic patients, making them therapeutic innovations compared to what is currently available,” states Dr. Tofé.

Earlier medications in this category include Ozempic (semaglutide) and Saxenda (liraglutide), among others already on the market, which are being used successfully while awaiting the results of new molecules.

The trials conducted by Dr. Tofé involve different phases: “We are talking about phase 3 clinical trials, which primarily measure the efficacy and safety of molecules not yet commercialized. This is the case with the second trial, which involves the molecule retatrutide.”

Regarding the other molecule, tirzepatide, it is already marketed under the name Mounjaro and is available in pharmacies by prescription. “This new drug has made headlines for its high efficacy in treating a prevalent condition such as overweight and obesity,” notes Dr. Tofé.

The studies at Juaneda Hospitals aim to “determine whether the use of these molecules in obese patients with high cardiovascular risk (after heart attacks, diabetes, or kidney disease) over three to five years leads to a lower incidence of mortality or cardiovascular events.”

Patients are selected based on specific criteria and offered the opportunity to participate in the clinical trial with full safety. “Today’s clinical trials define the medications doctors will prescribe tomorrow, just as the drugs prescribed today are the result of yesterday’s clinical trials,” emphasizes Dr. Tofé.

“Our team has been conducting clinical research for 15 years,” he highlights, adding that “these trials are audited by health authorities, pharmaceutical sponsors, and regulatory agencies, in our case the European Medicines Agency (EMA).”

“In the clinical development of a molecule, from its conception in a laboratory to its availability in pharmacies, the first evaluations focus on safety, which is assessed in phase I and II studies,” he explains.

“Only when molecules successfully pass these stages without evidence of potentially dangerous effects do they advance to the next phase, where their efficacy for the intended purpose is evaluated. Safety is the foundation of drug development.”

Currently, with the emergence of these molecules and their predecessors, “we are witnessing a paradigm shift in the management of obesity as a disease and a pandemic affecting the developed world, with prevalence rates of 25–30% or higher. In countries like the United States, obesity affects over 50% of the population.”

Until now, the management of this condition “has primarily relied on lifestyle modifications, including proper diet, exercise, avoiding sedentary behavior, and limiting alcohol consumption and high-calorie processed foods. These were the only tools available, aside from bariatric surgery in severe cases.”

“Today, this is changing. We now have medications that, when applied to patients with various degrees of obesity, achieve significant weight loss. Of course, this must be combined with reasonable diets and healthy lifestyle practices—messages that will always remain relevant because they never lose importance,” concludes Dr. Tofé.