Japan Study: Imeglimin + DPP-4 Inhibitor Cuts HbA1c by 1%

A Study from Japan Shows a Drug Combination May Dramatically Improve Blood Sugar Control

A study from Japan, conducted at Toho University Graduate School of Medicine in Tokyo, explored whether combining two diabetes medications — imeglimin and a DPP-4 inhibitor — could meaningfully improve blood sugar control in people with Type 2 diabetes. The results, published in Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy in 2025, are generating interest among diabetes specialists worldwide.

What Is Imeglimin — and Why Haven't Americans Heard of It?

Imeglimin is a newer oral diabetes medication approved in Japan in 2021. It works differently from most existing drugs by targeting the mitochondria (the energy centers of cells) to boost insulin secretion and improve how the body uses glucose. While it is not yet FDA-approved in the United States, it represents a new class of diabetes treatment that researchers are watching closely.

DPP-4 inhibitors — sold in the US under brand names like Januvia (sitagliptin), Tradjenta (linagliptin), and Onglyza (saxagliptin) — are among the most commonly prescribed diabetes medications in both Japan and the United States. Japan's prescribing patterns are notably similar to those in the US, making this research especially relevant for American patients.

What the Japanese Researchers Found

Eleven patients with Type 2 diabetes already taking a DPP-4 inhibitor were given 1,000 mg of imeglimin twice daily for 16 weeks. Here's what happened:

• HbA1c dropped from 7.5% to 6.5% — a full percentage point improvement, bringing the average participant to the American Diabetes Association's (ADA) target of below 7%.
• Casual blood glucose improved from 168 mg/dL to 128 mg/dL — moving from a clearly elevated level into a much healthier range. (These measurements were already reported in mg/dL, the standard used in the US.)
• Time in Range (TIR) jumped from 65% to 90% — meaning participants spent significantly more hours each day with blood sugar in a healthy range (typically 70–180 mg/dL). The ADA recommends a TIR goal of above 70% for most adults.
• Time Above Range fell from 34% to just 9% — a dramatic reduction in dangerous high-glucose periods.

Importantly, researchers found that imeglimin improved the body's ability to secrete insulin in response to food (glucose-stimulated insulin secretion), without worsening insulin resistance or disrupting glucagon — the hormone that raises blood sugar.

Why This Matters for US Patients

Many American patients with Type 2 diabetes take DPP-4 inhibitors as their primary medication, yet still struggle to reach their HbA1c targets. This Japanese research suggests that imeglimin could eventually serve as a powerful add-on therapy for exactly this group of patients. The drug's unique mechanism — improving insulin secretion through a different pathway than DPP-4 inhibitors — means the two drugs may work synergistically rather than redundantly.

The improvement in Time in Range is particularly meaningful. US diabetes care is increasingly focused on TIR as a real-world measure of glucose management, especially for patients using continuous glucose monitors (CGMs). A jump from 65% to 90% TIR in just 16 weeks is a clinically significant finding.

Imeglimin is currently under review and investigation for potential markets outside Japan. American patients and their doctors should watch for future FDA submissions and larger clinical trials.

Study Citation

Itsukaichi, Yoshikawa, & Fuchigami. (2025). Effect of Imeglimin, a Novel Anti-Diabetic Agent, on Insulin Secretion and Glycemic Variability in Type 2 Diabetes Treated with DPP-4 Inhibitor: A 16-Week, Open Label, Pilot Study. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. PMID: 39807125. DOI: 10.2147/DMSO.S495930