Interestingly, there is evidence that underlying insulin sensitivity in part modulates the response of metformin on proliferation, with more beneficial effects observed in patients with homeostatic model assessment for insulin resistance (HOMA-IR) > 2.8, indicating that tumors from patients with insulin resistance were more receptive to metformin [105,106], likely because metformin has been shown to reduce several markers of metabolic health, including body weight, HOMA-IR, cholesterol, and leptin [101,107]. The gene discussed is INS; the disease is Insulin resistance.