Experimental weight loss pill boosts metabolism — but doesn’t make you eat less

One of the first things you’ll notice after getting on a GLP-1 drug like Ozempic or Wegovy is that food becomes a lot less interesting.

For many, that’s a godsend. It turns off “food noise” that makes people eat compulsively, or when they’re not hungry.

For others, it sucks the desire, pleasure, and satisfaction out of eating. One Reddit user on Wegovy writes, “I love food, and I really miss enjoying it.”

“I can’t eat for pleasure anymore,” another person on Ozempic wrote. “I can’t even eat if I truly want to if I am not at all hungry.”

Unfortunately, that’s a key part of how GLP-1s work — eat less, lose weight. But what if you didn’t have to lose your appetite?

A new experimental drug could be opening the door to that possibility.

Authors of a new study found that in mice, a compound called TOFA turned on genes that help cells burn fat and generate energy, boosting metabolism.

A big problem for GLP-1 users

An astonishing 11% of US adults are on a GLP-1 for weight loss. For some, reduced appetite is simply an inconvenient necessity. But for others, it can cause serious issues.

Because they’re eating a lot less, people on GLP-1s are often deficient in a number of key nutrients, from vitamin D, to calcium and iron, causing conditions like anemia. That can become malnutrition and sarcopenia, or loss in muscle mass and function.

What is TOFA?

While GLP-1s largely work by controlling appetite, TOFA (5-tetradecyloxy-2-furoic acid) works by spending more energy.

Body weight responds to those two levers, said Anders Näär, a senior author of the study: “GLP-1s work almost entirely on the first, so we went after the second.”

The mice who had TOFA lost weight but didn’t lose significant amounts of lean muscle. They burned 18% more energy without changes to physical activity or body temperature.

TOFA was able to block production of new fatty acids (lipids) in the liver, and unlike other drugs in its class, didn’t raise triglyceride levels in the blood. High triglyceride levels can raise risks of heart attack, stroke, and heart disease.

TOFA also improved insulin sensitivity (over time, low sensitivity can lead to diabetes) and kept blood sugar within normal levels, while improving features of fatty liver disease.

Researchers compared TOFA to using 2 separate compounds, one to block lipids (Firsocostat) and one to boost energy (sold under the brand Iqirvo), but found the combination wasn’t as effective as TOFA.

Then, TOFA was used with GLP-1s together. Researchers found that using them together was better than using either one alone. This was shown across body weight, glucose control, insulin levels and triglycerides.

Näär said they see TOFA as possible complementary treatment to GLP-1s rather than a replacement.

All that said, these tests were only done on mice for now. The safety and efficacy of TOFA for humans isn’t yet known.