Dual amylin and calcitonin receptor agonist treatment improves insulin sensitivity and increases muscle-specific glucose uptake independent of weight loss

Are insulin sensitizers the new strategy to treat Type 1 diabetes? A long‐acting dual amylin and calcitonin receptor agonist improves insulin‐mediated glycaemic control and controls body weight

“…KBP-336 reduced fasting blood glucose levels, similarly to lean controls, when combined with either dose of Humulin. These data indicate that KBP-336 improves insulin sensitivity and thereby lowers insulin requirements, which is in line with recent studies showing that DACRAs improved insulin sensitivity in T2D rats during a hyperinsulimic glucose clamp (Larsen et al, 2022;Larsen, Melander, et al, 2023).…”

“…Moreover, pancreatic and insulin were elevated in rats treated with KBP-336. It has previously been suggested that the DACRA salmon calcitonin improved pancreatic beta-cell function and beta-cell area in diabetic rats (Feigh et al, 2012), which together with the insulin-sensitizing effect (Larsen, Melander, et al, 2023) and the present findings could imply the KBP-336 contributes to pancreatic beta-cell preservation. This, coupled with the enhanced insulin sensitivity caused by KBP-336, raises the possibility of using KBP-336 as a standalone treatment.…”

“…As a result, there is no clear evidence on whether KBP-336 can reduce the risk of hypoglycaemia. Interestingly, DACRAs are insulin sensitizers (Larsen, Melander, et al, 2023), which is opposite to the insulinotropic action of GLP-1 analogues (Holst, 2007;Ladenheim, 2015;Vilsbøll et al, 2008). Therefore, the likelihood of hypoglycaemic events should be lower with DACRAs than with GLP-1 analogues, which stimulate postprandial insulin secretion.…”

“…Therefore, it is essential to validate the dosing regimen further and potentially decrease insulin dose when administering a DACRA, because it improves insulin sensitivity and thus reduces insulin requirements (Larsen, Melander, et al, 2023). However, the effects on blood glucose levels were maintained, even after switching to a pump with an adjusted Humulin dose on day 21.…”

“…diabetes (Larsen et al, 2022;Larsen, Melander, et al, 2023). Moreover, treatment with the DACRA, salmon calcitonin, was proposed to enhance the function of pancreatic beta-cells and increase beta-cell area in Zucker diabetic fatty (ZDF) rats (Feigh et al, 2012).…”