Tirzepatide, a diabetes drug, helped a CGL patient control blood sugar better than leptin—even though leptin is made of fat, and tirzepatide isn’t! This could change how we treat metabolic diseases.
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Only a few thousand people worldwide are affected by
Fat builds up in organs like the liver when there is no fat tissue for appropriate storage, which causes severe insulin resistance and diabetes.
Tirzepatide Offers a Less Painful, More Affordable Alternative
Researchers from Rutgers Health have discovered that for patients with a rare hereditary form of lipodystrophy that leaves them with nearly no fat tissue, a weekly injection of diabetic medication could take the place of uncomfortable daily hormone shots. The study was published in The New England Journal of Medicine (1
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Tirzepatide for Congenital Generalized Lipodystrophy
).
“Due to their severe insulin resistance, these patients have a significantly shortened life expectancy,” said Christoph Buettner, the study’s senior author and chief of endocrinology, metabolism, and nutrition at Rutgers Robert Wood Johnson Medical School.
Currently, the standard treatment for CGL involves daily injections of metreleptin, a synthetic version of the hormone leptin, which is naturally produced exclusively by fat tissue. However, daily leptin shots are both expensive – costing hundreds of thousands of dollars annually – and particularly painful for CGL patients.
“When you inject yourself with, for example, insulin, you inject into subcutaneous fat, but these patients don’t have that,” said Svetlana Ten, associate professor of pediatrics and first author of the study. “Each injection is painful.”
In a recent study, researchers explored if diabetes and obesity drug tirzepatide (the active ingredient in Zepbound and Mounjaro) could improve CGL, as it improves insulin resistance. Tirzepatide is administered through a weekly injection, potentially reducing the burden and pain associated with CGL treatment. It is also much more affordable than metreleptin.
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Tirzepatide Successfully Controls Blood Sugar in Congenital Generalized Lipodystrophy Patients
The first patient, a 23-year-old man who had refused the painful daily treatments with leptin and insulin for 2 years, saw his average blood glucose drop from 252 to 128 milligrams per deciliter after three weeks on the maximum dose of tirzepatide.
His blood glucose, which had been at healthy levels between 70 and 140 milligrams per deciliter in 8% of readings, remained at healthy levels in 93% of readings, an almost complete normalization without the need to inject insulin.
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The second patient, a 64-year-old woman who required supplemental insulin injections because leptin alone couldn’t control her blood glucose, achieved normal blood glucose levels with tirzepatide alone.
“The surprise here was that when we stopped leptin and gave tirzepatide, the patient was very well controlled, probably better than while she was taking leptin,” Buettner said.
“Leptin is an important hormone, made only by fat tissue, that is an important regulator of metabolism, so leptin therapy made intuitive sense in patients with CGL. The hormone GLP1, which is mimicked by tirzepatide, is not made in adipose tissue, and while tirzepatide is an insulin sensitizer, we did not expect it would have such potency in patients with CGL.”
While both tirzepatide and leptin work in the brain, they do so through different signaling pathways, acting on different neurons in distinct brain regions. This suggests that leptin and GLP1 signaling may have more extensive overlap than so far suggested.
The researchers plan a larger trial to validate these initial results, though recruiting enough patients will be challenging given the condition’s rarity.
If the results hold up in larger studies, tirzepatide could offer CGL patients an easier and potentially more affordable treatment option. However, Buettner said more research is needed to evaluate both the long-term efficacy and safety in this specific patient population and beyond that in other leptin-deficient conditions.
Reference:
- Tirzepatide for Congenital Generalized Lipodystrophy- (https://www.nejm.org/doi/10.1056/NEJMc2413871)
Source-Eurekalert