A new animal study presented reveals how two leading anti-obesity drugs, tirzepatide and semaglutide, uniquely influence the body’s energy use during and after treatment.
Researchers have discovered that tirzepatide and semaglutide
impact energy metabolism in distinct ways.
New animal research presented at this
year’s European Congress on Obesity (ECO) in Malaga, Spain (May 11 to 14) has
uncovered surprising differences in how two popular weight-loss medications
affect the body’s metabolism. The study shows that tirzepatide temporarily
boosts the body’s energy use, while semaglutide initially slows it down. These
changes happen quickly after treatment begins and fade just as fast once the
medication is stopped.
Tirzepatide and semaglutide are two
breakthrough anti-obesity drugs that have gained attention for their impressive
ability to support weight loss and improve metabolic health. These medications
belong to a class known as GLP-1 receptor agonists, or dual agonists, which
work mainly by reducing appetite and helping the body manage blood sugar more
effectively.
As co-leading author Dr. Simone Bossi
from the Pharmacology Research department at Gubra, a preclinical contract
research organisation and biotech company in Denmark, explained, “Weight is
largely determined by the balance between the energy consumed and the amount of
energy expended. Eating more and burning less energy creates a positive energy
balance, leading to weight gain, while eating less and burning more creates a
negative balance, resulting in weight loss. We know that tirzepatide and
semaglutide tip the scales towards a negative energy balance by lowering
appetite and food intake.”
However, their acute and long-term
effects on energy expenditure and metabolic adaptations—the physiological
adjustments the body makes to conserve energy in response to a reduction in
calorie intake—after treatment cessation remain poorly understood.
A High-Fat Diet and Real-Time Monitoring
In this study, researchers fed a group
of 24 mice of the same age a high-fat diet for 20 weeks Then they were divided
into three groups (8 per group): a vehicle control (no treatment), a
semaglutide group (10 nmol/kg), and a tirzepatide group (10 nmol/kg). The mice
were given the drugs once a day for four weeks, followed by a two-week washout
period, and the fatty diet was maintained throughout the period.
Energy expenditure was continuously
monitored in real time with indirect calorimetry (which measures oxygen
consumption and exhaled carbon dioxide and helps estimate energy usage)
alongside measurements of food and water intake and physical activity levels.
The experiment was conducted at
thermoneutrality (ambient temperatures where metabolic rate is at a minimum) to
minimize confounding effects of cold-induced thermogenesis (burning calories to
generate heat).
After four weeks of treatment, the
control animals (given no treatment) displayed a weight gain of 2.7 grams (g)
on average, while those given tirzepatide and semaglutide lost on average 15.6g
and 8.3g respectively, with the most pronounced effects occurring in the first
week. Both tirzepatide and semaglutide also led to a notable reduction in food
intake.
The study found a significant increase
in energy expenditure after four days of tirzepatide treatment, which remained
elevated throughout the second week before gradually returning to control
levels. Importantly, this increase was not accompanied by a rise in physical
activity, indicating a direct metabolic effect. However, the washout period
after treatment stopped revealed no lasting differences in metabolic profiles
as the mice started to eat more than before.
In contrast, treatment with
semaglutide resulted in a significant reduction in energy expenditure during
the first three days of dosing, followed by a return to control levels.
Energy Efficiency and Fat Utilization
“When people lose a lot of weight,
their bodies often use less energy, which can make it harder to keep weight
off,” explained Dr. Bossi. “As seen in this study, mice receiving semaglutide
did show a slowing down of burning energy during weight loss.”
Nevertheless, tirzepatide and
semaglutide both led to a decrease in the respiratory exchange ratio during the
first two weeks of treatment, suggesting an increase in fat oxidation and a
decrease in carbohydrate oxidation rates, thereby aiding weight loss.
Respiratory exchange ratio levels returned to control levels after three weeks
of dosing, but increased again during the washout period when the mice started
to eat a lot again.
According to Dr. Bossi, “Our findings
suggest distinct metabolic adaptations to semaglutide and tirzepatide
treatment. Both medications facilitate substantial weight loss and also enhance
fat oxidation. But while semaglutide initially appears to slow down the burning
of energy during weight loss, tirzepatide temporarily increases the burning of
energy. It is this effect on energy expenditure at the beginning of dosing that
might help explain why tirzepatide has a stronger effect on weight loss.”She
adds, “This preliminary work opens exciting avenues for future research to
clarify the underlying mechanisms and to develop new improved therapies
focusing on increasing energy expenditure for long-term weight maintenance.”
No comments:
Post a Comment