Type 2 Diabetes and Pre-Diabetes

Diabetes affects over 38 million Americans. Type 2 diabetes mellitus (T2DM) is responsible for over 90% of these cases. Reports suggest that metformin is the most frequently prescribed T2DM medication due to its ability to lower glucose effectively while producing few side effects.  

In TRIPLN^®, NuSirt combines metformin with L-leucine and sildenafil. All three of TRIPLN^®’s components independently converge upon the sirtuin signaling pathway (either directly or indirectly) and generate a synergistic positive feedback loop in TRIPLN^® to increase insulin sensitivity. Moreover, while metformin primarily acts on the liver, the effects of L-leucine and sildenafil are more broadly distributed. Thus, the synergistic, wide-reaching effects of TRIPLN^® make it a promising alternative to metformin. 

Additionally, while metformin targets hyperglycemia, TRIPLN^® has shown promise in treating other conditions associated with diabetes, including hypertension, MAFLD/MASH, and obesity. While other classes of anti-diabetics, like GLP-1 receptor agonists and SGLT2 inhibitors, also alleviate these conditions, their tolerability profiles make them undesirable for many patients. 

By contrast, TRIPLN^® appears to be well-tolerated. Patients taking metformin alone report mild, dose-dependent gastrointestinal side effects, such as nausea, vomiting, and diarrhea. Because TRIPLN^® uses a lower amount of metformin to produce the same level of glycemic control, the incidence even of these mild side effects should shrink.  

We have completed one Phase 2 trial using TRIPLN^® to treat T2DM, with promising results. We have also evaluated TRIPLN^®’s potential in patients with pre-diabetes.