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Only pramlintide is approved with insulin. However, its short half\u2010life limits efficacy, requiring multiple daily injections and increasing hypoglycaemia risk. New strategies are needed to improve glycaemic control. Dual amylin and calcitonin receptor agonists are potent insulin sensitizers developed for Type 2 diabetes (T2D) as they improve glucose control, reduce body weight, and attenuate hyperglucagonemia. However, it is uncertain if they could be used to treat T1D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Sprague Dawley rats received a single intravenous injection of streptozotocin (STZ) (50\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) to induce T1D. Humulin (1\u2009U\/200\u2009g\u00b7day<jats:sup>\u22121<\/jats:sup> or 2\u2009U\/200\u2009g\u00b7day<jats:sup>\u22121<\/jats:sup>) was continuously infused, while half of the rats received additional KBP\u2010336 (4.5\u00a0nmol\u00b7kg<jats:sup>\u22121<\/jats:sup> Q3D) treatment. Bodyweight, food intake, and blood glucose were monitored throughout the study. An oral glucose tolerance test was performed during the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Treatment with Humulin or Humulin + KBP\u2010336 improved the health of STZ rats. Humulin increased body weight in STZ rats, but KBP\u2010336 attenuated these increases and maintained a significant weight loss. The combination exhibited greater blood glucose reductions than Humulin\u2010treated rats alone, reflected by improved HbA1c levels and glucose control. The combination prevented hyperglucagonemia, reduced amylin levels, and increased pancreatic insulin content, indicating improved insulin sensitivity and beta\u2010cell preservation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The insulin sensitizer KBP\u2010336 lowered glucagon secretion while attenuating insulin\u2010induced weight gain. Additionally, KBP\u2010336 may prevent hypoglycaemia and improve insulin resistance, which could be a significant advantage for individuals with T1D seeking therapeutic benefits.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16329","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:38:38Z","timestamp":1708475918000},"page":"1829-1842","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Are insulin sensitizers the new strategy to treat Type 1 diabetes? 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