A diabetes medication might be more effective than expensive injections for individuals with a rare genetic disorder, as suggested by a study from Rutgers Health.
Researchers from Rutgers Health have discovered that a once-weekly diabetes medication can potentially replace the painful daily hormone injections needed for patients with a rare genetic condition known as lipodystrophy, which causes them to have almost no fat tissue left, according to findings published in The New England Journal of Medicine.
Congenital generalized lipodystrophy (CGL) is a rare condition affecting only a few thousand individuals around the globe. It leads to severe metabolic issues, diabetes, insulin resistance, and shorter life spans. Due to the lack of fat tissue for storing fat properly, excess fat builds up in critical organs like the liver, resulting in significant insulin resistance and diabetes.
“Patients with this condition are seriously ill and have a much lower life expectancy because of intense insulin resistance,” stated Christoph Buettner, the head of endocrinology, metabolism, and nutrition at Rutgers Robert Wood Johnson Medical School and the study’s senior author.
The current treatment for CGL requires daily injections of metreleptin, a synthetic version of the hormone leptin, which is normally produced by fat tissue. However, this daily regimen is not only very costly—amounting to hundreds of thousands of dollars each year—but also particularly painful for these patients.
“Unlike insulin injections, which can be administered into subcutaneous fat, these patients lack that option, making each shot quite painful,” explained Svetlana Ten, an associate professor of pediatrics and the study’s lead author.
The recent research investigated whether tirzepatide, a drug used for diabetes and obesity (also found in Zepbound and Mounjaro), could alleviate the symptoms of CGL. Tirzepatide is given as a weekly injection, potentially lessening the treatment burden and pain experienced by patients. Additionally, it is significantly more affordable than metreleptin.
The first patient in the study, a 23-year-old man who had avoided painful daily leptin and insulin treatments for two years, experienced a drop in his average blood glucose from 252 to 128 milligrams per deciliter after just three weeks on the maximum tirzepatide dosage. Initially, his blood glucose levels were healthy in only 8% of readings, but after starting tirzepatide, he maintained healthy levels in 93% of readings—effectively normalizing his levels without needing insulin injections.
The second participant, a 64-year-old woman who needed additional insulin shots because leptin alone couldn’t manage her blood sugar, reached normal blood glucose levels using tirzepatide alone.
“What surprised us was that after stopping leptin and switching to tirzepatide, the patient was incredibly well-controlled, likely even better than when she was taking leptin,” Buettner remarked. “Leptin plays a crucial role in the body, being produced solely by fat tissue, so treating patients with CGL with leptin seemed logical. Interestingly, GLP1, which tirzepatide mimics, is not produced in fat tissue, and while it’s intended to enhance insulin sensitivity, we didn’t expect it to work so effectively in CGL patients.”
Both tirzepatide and leptin influence the brain, but they do so via different signaling pathways affecting various neurons across distinct brain regions. This implies that the interactions between leptin and GLP1 signaling are likely more complicated than previously thought.
The research team is planning a larger study to confirm these initial findings, although enrolling enough patients could prove difficult due to the rarity of the condition.
If the findings are validated in more extensive trials, tirzepatide could become a simpler and potentially cheaper treatment option for those with CGL. However, Buettner emphasized that further studies are necessary to explore both the long-term effectiveness and safety of tirzepatide for this specific group and for other leptin-deficient conditions.
