Experimental diabetes drug delivers a striking 44% reduction in body fat

Diabetes affects millions around the globe, often leading to insulin resistance and fatty liver disease.

HPH-15 lowers diabetes risks with 200 times greater potency than Metformin

HPH-15 lowers diabetes risks with 200 times greater potency than Metformin. (CREDIT: Shutterstock)

Diabetes affects millions around the globe, often leading to insulin resistance and fatty liver disease. Effective treatments must not only control blood sugar but also prevent these serious complications.

A research team from Kumamoto University has now introduced HPH-15, a compound offering fresh possibilities for diabetes care. Unlike standard therapies, it regulates glucose while tackling obesity-related problems, signaling a meaningful advance in treatment.

The compound works by activating AMP-activated protein kinase, or AMPK. This enzyme is vital for energy control in cells. Through this pathway, HPH-15 lowers glucose levels and reduces fat buildup at the same time.

Early lab results revealed remarkable performance. Compared with metformin, one of the most widely used diabetes drugs, HPH-15 achieved equal or better effects with far lower doses, strengthening its promise as a therapy.

Graphical abstract showing HPH-15's performance versus Metformin across various metrics. (CREDIT: Diabetologia)

Tests on liver, muscle, and fat cells confirmed wide-ranging benefits. HPH-15 reliably activated AMPK, improved glucose uptake, and drove GLUT4 proteins to the cell surface—an essential process for healthy blood sugar control.

Even more striking, it reached these outcomes at concentrations 200 times lower than metformin. It also caused equal or less lactic acid buildup, lowering the chance of lactic acidosis, a common metformin concern.

Animal trials added further support. Mice fed high-fat diets responded with improved insulin sensitivity and sharp drops in blood sugar. Levels fell from 11.1 mmol/L to 7.9 mmol/L, even at low doses, results usually seen only with large amounts of metformin.

Beyond blood sugar, HPH-15 shielded against obesity-linked damage. Treated mice showed less fat buildup, healthier livers, and a striking 44% reduction in subcutaneous fat, underscoring the drug’s potential for managing both diabetes and obesity.



“This compound holds transformative potential for diabetes treatment, offering benefits beyond blood sugar regulation,” noted Professor Mikako Fujita from the Faculty of Life Sciences at Kumamoto University. The research, published in the prestigious journal Diabetologia, emphasizes the multifaceted impact of HPH-15.

One of the most critical findings involves the compound’s antifibrotic properties. Liver fibrosis is a common complication in patients with type 2 diabetes, often exacerbated by fat accumulation and chronic inflammation. HPH-15’s ability to reduce fibrosis adds another layer of therapeutic value, setting it apart from existing medications like metformin. These effects could address unmet needs for individuals at risk of severe liver damage.

Safety remains a top priority in diabetes treatment. While metformin has long been a standard therapy, its use is sometimes limited due to side effects, including lactic acidosis.

In contrast, HPH-15’s lower production of lactic acid suggests a safer profile, particularly for patients with underlying health conditions. The compound’s ability to activate AMPK and reduce glucose levels without excessive lactic acid production could represent a safer alternative for a broader range of patients.

Effects of HPH-15 on blood glucose and insulin in HFD-fed mice. (a) Schematic of the mouse experiments. (b) Quantification of random glucose levels in the blood of mice treated with HPH-15 (fed ad libitum). (CREDIT: Diabetologia)

Dr. Hiroshi Tateishi and Professor Eiichi Araki, leading the Kumamoto University research team, emphasize the significance of these findings. “HPH-15 not only matches but exceeds the capabilities of metformin in several key areas, including fat reduction and antifibrotic effects. This positions it as a versatile tool in combating diabetes and its complications,” they explained.

The implications of this research extend beyond individual patients. Type 2 diabetes is a growing global epidemic, contributing to substantial healthcare costs and reduced quality of life for millions.

Current treatment options often focus narrowly on blood glucose levels, leaving other issues like obesity and liver damage inadequately addressed. HPH-15’s multifunctional benefits could redefine diabetes care by offering a holistic approach to managing the condition.

What is Metformin?

Metformin, a medication with roots tracing back hundreds of years, was initially derived from the herb Galega officinalis, traditionally used in Europe for digestive and urinary health.

Lipid level assessment by Oil Red O staining of HepG2 cells treated with HPH-15 or metformin for 16 h followed by exposure to 100 mmol/l d-(+)-glucose for 1 day; the cells were observed using a microscope. (CREDIT: Diabetologia)

In 1918, scientists identified guanidine, a compound in the herb, as a blood sugar-lowering agent, leading to the development of medications like metformin and phenformin. However, concerns over phenformin’s severe side effects and the discovery of insulin overshadowed these drugs.

Decades later, metformin was rediscovered and approved in Europe in the 1950s as a diabetes treatment, gaining FDA approval in the United States in 1995. Today, it is a cornerstone treatment for people with diabetes who cannot manage their blood sugar through lifestyle changes alone.

Beyond managing blood sugar, metformin offers additional benefits for individuals with diabetes, including improved cardiovascular health, reduced mortality from cardiovascular disease, and modest weight loss. These advantages have positioned metformin as one of the most prescribed diabetes medications worldwide.

Researchers have also explored its off-label uses, noting its effectiveness in conditions like prediabetes, gestational diabetes, and polycystic ovary syndrome (PCOS). Additionally, it has shown promise in mitigating weight gain caused by antipsychotic medications, further expanding its clinical applications.

HPH-15's performance versus Metformin in muscle, epididymal fat and liver. (CREDIT: Diabetologia)

Emerging research highlights metformin’s potential benefits for non-diabetic individuals. Studies suggest it may reduce the risk of cancers such as breast, colon, and prostate cancer in those with type 2 diabetes. Metformin has also been linked to a slower rate of cognitive decline, a lower risk of dementia, and fewer strokes in diabetic populations.

Fascinatingly, early studies indicate that metformin might slow aging, prevent age-related diseases, and even increase lifespan by enhancing insulin sensitivity, providing antioxidant effects, and improving vascular health.

However, most studies on metformin have focused on individuals with diabetes or prediabetes, leaving uncertainty about whether these potential benefits extend to the broader population. Ongoing research aims to clarify its impact on non-diabetic individuals and determine whether its unique effects could revolutionize preventative health care and anti-aging therapies.

Although the findings are promising, further research is necessary before HPH-15 can be introduced as a standard treatment. Clinical trials involving human participants will be critical to confirm its efficacy and safety. Nevertheless, these early results mark an important step forward in the fight against diabetes.

As researchers continue to explore the compound’s potential, HPH-15 offers hope for improved outcomes and enhanced quality of life for those living with diabetes.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.


Like these kind of feel good stories? Get The Brighter Side of News' newsletter.


Joshua Shavit
Joshua ShavitScience and Good News Writer

Joshua Shavit
Science & Technology Writer | AI and Robotics Reporter

Joshua Shavit is a Los Angeles-based science and technology writer with a passion for exploring the breakthroughs shaping the future. As a contributor to The Brighter Side of News, he focuses on positive and transformative advancements in AI, technology, physics, engineering, robotics and space science. Joshua is currently working towards a Bachelor of Science in Business Administration at the University of California, Berkeley. He combines his academic background with a talent for storytelling, making complex scientific discoveries engaging and accessible. His work highlights the innovators behind the ideas, bringing readers closer to the people driving progress.