Daewoong Pharmaceutical's SGLT-2 inhibitor, Envlo (enavogliflozin), has shown promise as a treatment option for metabolic diseases, offering possibilities beyond simply lowering blood sugar.

According to the results of a phase 3 clinical trial analysis presented at the American Diabetes Association (ADA) 2025 in Chicago, USA, June 20 to 23, Envlo significantly lowered leptin levels compared to dapagliflozin and showed significant improvements in various metabolic parameters, including insulin resistance, fasting insulin, fasting glucose, and urinary glucose-to-creatinine ratio.

Daewoong Pharmaceutical's SGLT-2 inhibitor, Envlo (enavogliflozin), has shown promise as a treatment option for metabolic diseases, offering possibilities beyond simply lowering blood sugar.

According to the results of a phase 3 clinical trial analysis presented at the American Diabetes Association (ADA) 2025 in Chicago, USA, June 20 to 23, Envlo significantly lowered leptin levels compared to dapagliflozin and showed significant improvements in various metabolic parameters, including insulin resistance, fasting insulin, fasting glucose, and urine/creatinine excretion ratio.

In particular, leptin levels were reduced in patients who lost less than 3 percent of their body weight, confirming the possibility of a direct effect on adipocyte function independent of weight change. Korea Biomedical Review spoke with Lee A-reum, the Medical Team Lead at Daewoong Pharmaceutical, who led the presentation of the results, about the significance of the study and its future directions.

Question: What was your primary purpose in attending the ADA?

Answer: We attended the conference to present the results of the significant improvement effects on adipokine and metabolic markers of Envlo, a homegrown SGLT-2 inhibitor, compared to dapagliflozin. Through this event, we announced that Envlo is a treatment option that can positively impact metabolism beyond glycemic control.

Q: In addition to the glycemic-lowering effects of Envlo in the study, we are curious about other clinical endpoints, including weight loss.

A: According to existing phase 3 study results, in addition to its glycemic-lowering effects, Envlo showed significant improvements in various metabolic markers, including lipid profile, insulin resistance, and blood pressure, with weight loss of about 5 percent from baseline.

In particular, the results presented at ADA were based on a pooled analysis of two phase 3 studies compared to the global SGLT-2 inhibitor dapagliflozin, which demonstrated statistically significant improvements in key metabolic endpoints, including leptin, fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and urinary glucose-to-creatinine ratio (UGCR) compared to the active control dapagliflozin. In particular, leptin levels were significantly reduced regardless of weight change, suggesting that Envlo may contribute to improved metabolic function by positively affecting adipocyte function itself.

Q: Why were leptin levels a key comparison?

A: Leptin is a key hormone secreted by adipocytes and is closely linked to appetite and energy metabolism, as well as insulin resistance and cardiovascular risk. In particular, a recent publication by The Lancet Diabetes & Endocrinology Commission implicated leptin in the pathophysiology of “clinical obesity,” making it a central player in the development of obesity and metabolic disease.

In particular, studies have shown that chronic elevations in leptin levels in patients with type 2 diabetes are associated with poor metabolic function and cardiovascular complications. Building on these studies, we sought to evaluate whether Envlo could have a broader range of metabolic effects beyond simply lowering blood glucose, including modulating adipose tissue function and energy homeostasis.

We previously showed that Envlo reduced insulin resistance in patients with type 2 diabetes by secreting more adiponectin and less leptin compared to placebo (presented at the American Society for the Study of Obesity last November). In a follow-up study, we found significant improvements in adipokines, including leptin, and changes in metabolic function with treatment compared to dapagliflozin.

Q: What follow-up studies are planned based on the Envlo data presented at the ADA?

A: As shown in this study, Envlo significantly reduced leptin levels independent of weight change. This is significant because it suggests a possible new mechanism by which Envlo directly affects adipocyte function.

We will continue to investigate the physiological pathways through which these differential effects of Envlo occur and how they may translate into clinical benefits for patients. These studies may ultimately lead to expanded therapeutic applications of Envlo in the future and contribute to more sophisticated patient-specific treatment strategies.