Comparable weight loss, yet approximately double the reduction in 'leptin'—suggesting class-specific metabolic variations among SGLT-2 inhibitors.
New diabetes drug 'Enblo' also improves insulin resistance, raising expectations as a therapy spanning beyond glycemic control to broader metabolic health.
Daewoong Pharmaceutical (069620) announced on the 28th that research results showing its novel diabetes drug "Enblo" (generic name: enavogliflozin) lowered blood leptin levels by approximately twice the magnitude of dapagliflozin, a fellow SGLT-2 inhibitor, have been published in the international journal Cardiovascular Diabetology.
The research team conducted a pooled analysis of two Phase III clinical trials for Enblo published in 2022. They evaluated 427 type 2 diabetes patients who participated in "ENHANCE-M," a study on metformin combination therapy, and "ENHANCE-D," a study on triple combination therapy with metformin and gemigliptin. Patients were administered either Enblo or dapagliflozin for 24 weeks, and subsequent changes were compared.
According to the analysis, the change in blood leptin levels after 24 weeks was -2.08 μg/L for the Enblo-treated group compared to -1.09 μg/L for the dapagliflozin group. The reduction in the Enblo group was approximately twice as large, and this difference persisted even after statistically adjusting for variations in weight loss between the two cohorts. Daewoong Pharmaceutical stated that these findings indicate class-specific metabolic effects that cannot be fully explained by weight loss alone.
The homeostasis model assessment of insulin resistance (HOMA-IR) score also showed a statistically significant improvement in the Enblo group (-1.36) compared to the dapagliflozin group (-1.05). Changes in leptin moved in tandem with HOMA-IR, insulin, and C-peptide—an indicator of insulin secretion. The data indicated that lower leptin levels correlated with improved insulin metabolism markers. Conversely, there were no differences between the two drugs in terms of glycated hemoglobin (HbA1c) or weight change.
Leptin is an appetite-regulating hormone secreted by fat cells that helps maintain constant body fat. Patients with type 2 diabetes, particularly those with obesity, frequently exhibit high blood leptin levels due to "leptin resistance," wherein the brain fails to properly process the signals despite adequate leptin secretion. This condition often coexists with insulin resistance.
Historically, reductions in leptin were considered a secondary consequence of weight loss. However, this study demonstrated differential leptin reductions between drugs even after controlling for weight changes, establishing a foundation to explore Enblo's potential in improving metabolic function. Nevertheless, the research team noted that the underlying mechanisms and long-term clinical implications require further investigation.
Professor Ryu Young-sang of Chosun University Hospital's Department of Endocrinology and Metabolism noted, "This study is significant in that Enblo demonstrated a greater reduction in leptin and significant improvements in insulin resistance markers compared to dapagliflozin, independent of weight change. Further research is needed to elucidate the mechanisms driving these changes."
Corresponding author Professor Park Chul-young of Kangbuk Samsung Hospital's Department of Endocrinology and Metabolism stated, "Adipose tissue dysfunction and insulin resistance are closely linked to cardiovascular, renal, and metabolic health. These findings can serve as a basis for exploring Enblo's metabolic role from a CKM (Cardiovascular-Kidney-Metabolic) perspective, though the long-term clinical significance warrants confirmation through follow-up studies."
Park Hyung-chul, head of Daewoong Pharmaceutical's ETC Marketing Division, remarked, "This holds great significance as Enblo demonstrated differentiated metabolic characteristics by showing a distinct reduction in leptin levels in a head-to-head comparison within the same SGLT-2 inhibitor class. Given that SGLT-2 inhibitors are valued as pivotal agents in CKM management, we will continue to build clinical evidence in alignment with this paradigm."
Enblo is a type 2 diabetes treatment developed by Daewoong Pharmaceutical belonging to the SGLT-2 inhibitor class. It lowers blood glucose by inhibiting glucose reabsorption in the kidneys and excreting excess sugar through urine.
