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• Researchers investigated whether triptans, commonly-used migraine drugs, induce weight loss in obese mice.
• They found that the drugs tested led to weight loss and improved glucose homeostasis in obese mice.
• The findings suggest a possible new target for weight loss therapies.

According to the Centers for Disease Control and Prevention (CDC), around 42% of people in the United States live with obesity, a condition linked to an increased risk of multiple health conditions like cardiovascular disease, cancer, and type 2 diabetes. Obesity is also associated with an increased risk of death from COVID-19.

Excessive caloric intake is known as the leading cause of weight gain. While researchers have identified obesity-linked genes and neural circuits linked to regulating satiety and food intake, until now, renovation mr k drug targets have remained scarce.

Since the 1960s, researchers have investigated the central serotonin system (5-HT) as a possible target for weight loss medications. Eventually, drugs were developed that targeted 5-HT 2C receptors (Htr2c). Examples included fen-phen and lorcaserin (Belviq), but both have since been withdrawn due to serious side effects.

Nevertheless, there are 14 other serotonin receptors, for which research is still ongoing to determine whether they affect appetite.

Further research into these receptors could help researchers develop drugs to reduce appetite in people with obesity.

Effect of triptans on weight loss

New research has found that triptans, a drug class widely used to treat acute migraine and cluster headaches, may also reduce weight in obese mice by targeting the serotonin 1B receptor (Htr1b). The study was recently published in the Journal of Experimental Medicine.

For the study, the researchers tested six prescription triptans on mice. They administered the drugs after an 18-hour fast and measured their post-fast food intake.

They found that four of the six triptans suppressed fasting-induced hunger and that frovatriptan yielded the strongest effect.

To find out how frovatriptan impacted food intake and weight, the researchers engineered mice to lack either Htr1b or Htr2c, the serotonin receptor targeted by fen-phen and lorcaserin. Frovatriptan had no effect in mice without Htr1b. However, it continued to affect mice who lacked Htr2c. The findings confirmed that the drug works by acting on Htr1b and not Htr2c.

The researchers next tested frovatriptan’s anti-obesity effects in diet-induced obese mice. To do so, they fed male mice a high fat diet for 7 weeks. The mice were then separated into two groups and treated with either frovatriptan or a saline solution while still fed a high fat diet.

They found that a daily dose of frovatriptan reduced body weight by an average of 3.58% within 24 days. Meanwhile, mice that were administered the saline solution experienced an average weight gain of 5.83% over the same period.

Mice infused with frovatriptan for 2 weeks experienced similar weight loss effects compared to controls. In addition, magnetic resonance analyses revealed that frovatriptan infusion reduced fat mass, but not lean mass, after 14 days. Frovatriptan-treated mice also exhibited improved glucose homeostasis in a glucose tolerance test.

“This is an interesting study that found that frovatriptan reduced appetite, food intake, and body weight in mice,” Dr. Glen D. Solomon, MACP, FRCP, professor and chair at the Department of Internal Medicine and Neurology at Wright State University, not involved in the study, told Medical News Today.

“If this study shows similar results in humans, it will offer another therapy for managing obesity. With the epidemic of obesity in Western culture, any effective therapy is welcome. Cost remains a major limitation in prescribing drugs for obesity. If a low cost generic medication were available, it could have a significant benefit to society.”
– Dr. Glen D. Solomon, MACP, FRCP

Underlying mechanisms

When asked how triptans work to reduce weight, Chen Liu, Ph.D., assistant professor at the Department of Internal Medicine and Neuroscience at The University of Texas Southwestern Medical Center, one of the study’s authors, told MNT:

“Triptans bind and activate the serotonin 1B receptors. We find these receptors in a small group of neurons in the hypothalamus that normally promotes food intake. Activation of serotonin 1B receptors in these cells inhibits their function and thus suppresses appetite.”

The researchers noted that as triptans tend to be used only in the short term for migraine, patients may not have noticed longer-term impacts on appetite and weight loss. When asked whether this means that frovatriptan may be safe for longer-term use, Dr. Liu said:

“The first generation of triptans such as sumatriptan can cause vasoconstriction and acutely increase blood pressure. As a result, they are not suitable for obese patients. In contrast, new generation triptans like frovatriptan had no effect on blood pressure or heart rate.”

“Furthermore, multiple clinical studies evaluating the cardiac safety of these drugs have shown they are relatively safe after frequent and long-term use even in patients with arterial hypertension or coronary artery disease,” he added.

The researchers concluded that their findings suggest that Htr1b is a new target for 5-HT-based weight loss therapies.

They added that future work is now warranted to comprehensively evaluate the effects of triptans and other Htr1b agonists on appetite, body weight, and safety.

When asked about the study’s limitations, Dr. Solomon noted that the study was conducted on mice, meaning it remains to be seen if the results translate to humans, too.

“We need to assess whether long-term triptan use provides long-term anorexic effects or if the appetite suppression is short-lived,” Dr. Solomon said. “We also need to assess the long-term safety of daily triptan use in a population already at increased risk of cardiovascular disease due to obesity and often diabetes.”

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