Even if the weight loss is similar, the amount of leptin decrease is about twice that… Diabetes drug 'Enblo' suggests differences in metabolic effects between SGLT-2 inhibitor classes, improving insulin resistance… "Expected to develop into a treatment that goes beyond blood sugar control and encompasses metabolic health."
A study showed that Daewoong Pharmaceutical's (069620) new diabetes drug 'Enblo' lowered blood leptin levels about twice as much as dapagliflozin, a drug in the same SGLT-2 inhibitor class. Although the weight loss and blood sugar improvement effects of the two drugs were similar, the leptin reduction and insulin resistance index improvement were greater in the Enblo treatment group.
Daewoong Pharmaceutical (CEO Chang-jae Lee and Seong-soo Park) announced on the 28th that the research results of Enblo (ingredient name: inavogliflozin) were published in the international academic journal 'Cardiovascular Diabetology'.
The researchers conducted an integrated analysis of two Enblo phase 3 clinical trials announced in 2022. Changes were compared among 427 patients with type 2 diabetes who participated in 'ENHANCE-M', a metformin combination therapy study, and 'ENHANCE-D', a metformin/gemigliptin triple combination therapy study, after receiving Enblo or dapagliflozin for 24 weeks.
As a result of the analysis, the change in blood leptin levels after 24 weeks was -2.08μg/L in the Enblo administration group and -1.09μg/L in the dapagliflozin administration group. The decrease in the Enblo administration group was approximately twice as large, and this difference was maintained even after statistically correcting for the difference in body weight change between the two administration groups. Daewoong Pharmaceutical explained this as a result suggesting differences in metabolic effects between drugs that cannot be explained by weight loss alone.
The change in insulin resistance index (HOMA-IR) in the Enblo administration group was -1.36, which was significantly improved compared to the dapagliflozin administration group (-1.05). Changes in leptin moved in the same direction as changes in HOMA-IR, insulin, and C-peptide, an indicator of insulin secretion. The explanation is that as leptin levels decrease, insulin metabolism indicators also tend to improve. On the other hand, there was no difference between the two drugs in glycated hemoglobin (HbA1c) and weight change.
Leptin is an appetite control hormone that is secreted from fat cells and helps maintain body fat at a constant level. Patients with type 2 diabetes, especially those with obesity, often have high blood leptin levels due to 'leptin resistance', which means the brain does not properly receive signals even when sufficient leptin is secreted. This tends to occur along with insulin resistance.
Until now, a decrease in leptin was thought to be a phenomenon accompanying weight loss. In this study, the extent of leptin reduction varied depending on the drug even after correcting for differences in weight change, providing evidence to explore the possibility of Enblo improving metabolic function. However, the researchers explain that the mechanism of action and long-term clinical significance must be confirmed through additional research.
Ryu Young-sang, a professor in the Department of Endocrinology and Metabolism at Chosun University, explained, "This study is meaningful in that Enblo lowered leptin to a greater extent than dapagliflozin even after correcting for body weight changes, and also showed significant improvement in insulin resistance indicators," adding, "Additional research is needed to identify the mechanism of action of these changes in the future."
Corresponding author Park Cheol-young, professor of endocrinology at Kangbuk Samsung Hospital, said, "Adipose tissue dysfunction and insulin resistance are closely linked to cardiovascular, kidney, and metabolic health, so these results can serve as a basis for exploring the metabolic role of Enblo from a CKM (cardiovascular-kidney-metabolic) perspective." He added, "The long-term clinical significance needs to be confirmed through follow-up research."
Park Hyeong-cheol, head of ETC Marketing Division at Daewoong Pharmaceutical, said, "It is significant in that Enblo showed differentiated metabolic characteristics by showing a difference in the extent of leptin reduction in direct comparison with the same SGLT-2 inhibitor class of drugs." He added, "As SGLT-2 inhibitors are evaluated as important drugs in CKM (cardiovascular-renal-metabolic) management, Enblo will also continue to create evidence in line with this trend."
Enblo is a type 2 diabetes treatment of the SGLT-2 inhibitor series developed by Daewoong Pharmaceutical. It works by lowering blood sugar by inhibiting glucose reabsorption in the kidneys and excreting sugar through urine.
