Up to 85.2% of type 2 diabetes mellitus (T2DM) patients are overweight or obese7, which increases risks of comorbidities like fatty liver disease and insulin resistance. Metformin is the first-line treatment for T2DM and acts via the AMP-activated protein kinase (AMPK) pathway. Another compound, HPH-15, is also found to act on the AMPK pathway, hence proposed as an alternative treatment to metformin. Toma et al. investigated the glucose-lowering effects of HPH-15 in high-fat diet (HFD)-fed mice, which mimics physiological changes observed in diabetic patients8. Results showed significant reductions in random and fasting blood glucose, as well as insulin levels with 10 mg/kg and 100 mg/kg HPH-15 treatment to comparable levels as 300 mg/kg metformin. Insulin sensitivity increased to similar levels as metformin and liver lipid accumulation also decreased significantly, which addresses the crucial aspects of fatty liver disease and insulin resistance in diabetes management. HPH-15 also exhibited unique subcutaneous fat deposition reduction and antifibrotic effects in the liver. This study shows that HPH-15 has comparable and additional effects at much lower doses than metformin, highlighting its potential for patients with diabetes complicated by obesity and fatty liver.
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