Park Chul-young, a leading endocrinologist at Kangbuk Samsung Hospital, led a post-hoc analysis project that uncovered adipokine improvements in existing clinical trial data — yielding three top-journal publications without a single new trial
"Global pharmaceutical companies pour enormous capital into large-scale research, but in Korea it costs more than 10 billion won ($7.5 million) just to conduct a single approval trial — making it difficult to pursue the same research model as global firms. The three published papers validated academic data through different analytical designs: a reduced renal function subgroup for blood glucose findings, a placebo-controlled group for adipokine findings, and a comparator drug group, among others."
Park Chul-young, a professor of endocrinology at Kangbuk Samsung Hospital, made those remarks Oct. 12 in an interview, explaining the significance of the "Data Generation Project" — a post-hoc analysis of phase 3 clinical trial data for Enablo (generic name: enavogliflozin), South Korea's 36th domestically developed new drug.
Park, a former president of the Korean Society for the Study of Obesity and currently the media and public relations director of the Korean Diabetes Association, is one of the country's foremost authorities on endocrine and metabolic diseases. He conceived and led the project with a focus on the organic link between diabetes treatment and obesity-related metabolic disorders.
The project, which Park spearheaded, brought together endocrinologists from four university hospitals — Hong Sang-mo of Guri Hanyang University Hospital, Ryu Young-sang of Chosun University Hospital, and Kim Kyung-soo of Bundang CHA Hospital — who formed an advisory panel and conducted post-hoc analyses of existing clinical data starting in 2024.
The results have been substantial. The research team completed presentations at five major international conferences, including the American Diabetes Association and the Endocrine Society, and went on to publish all three papers in Cardiovascular Diabetology, an international journal in the cardiovascular and diabetes field with an impact factor of 15.6.
Given that a single new approval trial typically costs more than 10 billion won, the three top-journal papers derived from existing phase 3 data represent clinical and academic value equivalent to roughly 30 billion won in research and development investment. In a domestic pharmaceutical and biotech ecosystem where limited capital often stunts follow-up research, the project has been recognized for establishing an academic evidence base for a Korean-developed drug through global journal placement — without the cost of a new trial.
"A single trial has a limited number of subjects, which makes it difficult to look closely at clinical indicators beyond the primary endpoints," Park said. "If you pool existing studies to secure a larger sample, you gain statistical power and can derive additional academic evidence." He described the project as a practical model for overcoming the funding and revenue constraints facing late-entry drugs while still building core clinical evidence.
The most notable academic finding was the rediscovery of adipokines — biomarkers that had been measured in the original trials but never analyzed. Adipokines are substances secreted by fat cells that play a role in regulating metabolic diseases.
"When we received the existing clinical data, we found measurements that had been taken but never used in the published analyses," Park said. "The most representative indicators were adipokines such as adiponectin and leptin. Through in-depth analysis of those, we were able to identify new possibilities for enavogliflozin to improve metabolic markers."
The three published papers validated their findings through different analytical designs: a reduced renal function subgroup, a placebo-controlled group, and a comparator drug group.
In the renal function subgroup analysis, enavogliflozin showed a statistically significant blood glucose-lowering effect compared with the comparator dapagliflozin, with a tendency to maintain stable efficacy even in patients with reduced kidney function.
A placebo-controlled study involving 160 patients with type 2 diabetes found that 24 weeks of enavogliflozin treatment not only increased adiponectin levels associated with weight loss, but also produced a weight-independent improvement — leptin levels fell significantly compared with the placebo group even after adjusting for the degree of weight reduction.
Finally, a pooled analysis of data from two phase 3 trials — ENHANCE-M and ENHANCE-D — covering 427 patients confirmed a greater reduction in blood leptin levels compared with the dapagliflozin group, with the gap remaining nearly twofold even after adjusting for weight loss. Reductions in HOMA-IR, a marker of insulin resistance, were also confirmed in both the enavogliflozin group (−1.36) and the dapagliflozin group (−1.05), and leptin reduction showed a significant positive correlation with improvements in HOMA-IR, insulin, and C-peptide levels.
Park interpreted the clinical significance of these biomarker changes as evidence of "qualitative improvement in fat cells." He said the root cause of chronic disease lies in fat cell dysfunction — specifically the abnormal proliferation and dysfunction of body fat, rather than weight figures alone. "In fat cells that have deteriorated from accumulated excess energy, beneficial hormones decrease while inflammatory cytokines increase, disrupting the hormonal system," he said.
"Leptin is a key hormone for maintaining weight homeostasis, but in patients with metabolic disorders it becomes excessively elevated and stops working — a condition known as leptin resistance," Park added. "The fact that enavogliflozin improved this can be interpreted as a signal of normalization in fat cell function."
However, because the findings are based on post-hoc, exploratory analyses, overinterpretation should be avoided. Enablo's officially approved indication remains blood glucose control in patients with type 2 diabetes, and changes in biomarkers do not in themselves constitute evidence of weight loss or obesity treatment efficacy.
"We confirmed changes in adiponectin and leptin through blood tests, but determining whether this reflects a direct mechanism of the drug is a question we are only beginning to address," Park said. "We are currently continuing animal studies to verify the underlying basic mechanisms."
Park also outlined a realistic strategy for the longer-term goal of positioning the drug as a global standard treatment. Large-scale trials directly measuring outcomes such as cardiovascular events or dialysis progression require enormous costs. "Given that the renal and cardiovascular protective effects of drugs in the same class have already been academically established, a practical approach for a late-entry Korean new drug would be to build the evidentiary link through real-world evidence — such as big data analysis from the National Health Insurance Service," he said.
silverpaper@heraldcorp.com
