Improved metabolic efficacy of a dual amylin and calcitonin receptor agonist when combined with semaglutide or empagliflozin

Nov 22, 2022European journal of pharmacology

Better metabolism with a combined amylin-calcitonin receptor activator and semaglutide or empagliflozin

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Abstract

Treatment with KBP-066A and semaglutide lowered body weight by 21% in combination, compared to 13% and 9.7% with each drug alone.

KBP-066A paired with semaglutide significantly reduced body weight in high-fat diet rats.
The combination of KBP-066A and semaglutide demonstrated greater efficacy than either drug alone.
KBP-066A in combination with semaglutide or the SGLT2 inhibitor empagliflozin lowered fasting blood glucose and HbA1C levels in diabetic rats.
The findings suggest KBP-066A may enhance the effects of existing diabetes and obesity treatments.

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Pharmacotherapies for obesity and type 2 diabetes (T2D) are thought to bridge the gap between lifestyle modification and the weight loss obtained with bariatric surgery. Although the effect of monotherapies, namely amylin and glucagon-like peptide-1 receptor (GLP-1R) agonists, has shown great potential, combination therapy is now becoming a strategy to optimize efficacy for weight management while minimizing adverse effects. This study investigated a dual amylin and calcitonin receptor agonist (DACRA); KBP-066A in combination with the GLP-1R agonist semaglutide or the sodium-glucose co transporter-2 inhibitor (SGLT2i) empagliflozin for anti-obesity and anti-diabetic treatment. The effect of KBP-066A, semaglutide, and empagliflozin alone and in combination was studied with respect to their impact on body weight, food intake, and glucose metabolism in high-fat diet (HFD) and Zucker diabetic fatty (fa/fa) (ZDF) rats. Treatment with KBP-066A and semaglutide lowered body weight by 13% and 9.7%. In contrast, a combination of both KBP-066A + semaglutide reduced body weight by 21% in HFD rats demonstrating superiority compared to monotherapies alone. A combination of KBP-066A with semaglutide or empagliflozin significantly lowered fasting blood glucose, and HbA1C (%) levels in ZDF rats. The complementary action by KBP-066A to GLP-1R agonist and SGLT2i on BW, food intake and glucose control endorsed the potential of DACRAs as an add-on therapy to therapeutic options for T2D and obesity.

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Improved metabolic efficacy of a dual amylin and calcitonin receptor agonist when combined with semaglutide or empagliflozin

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