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| Potential Oral Incretin / Islet Therapy |
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MBX-2982 is a potential first-in-class treatment for type 2 diabetes that targets G protein-coupled receptor 119 (GPR119), a receptor that interacts with bioactive lipids known to stimulate glucose-dependent insulin secretion. Preclinical data indicate that MBX-2982 is a potent selective orally-active GPR119 agonist that functions through a unique dual mechanism of action. First, it acts directly on the beta cell to increase insulin secretion. In addition, MBX-2982 stimulates release of the incretin GLP-1 from the gut. This dual action is unique and may offer improved glucose homeostasis over existing diabetes therapies, with potential for weight loss and improved islet health.
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MBX-2982 has completed three Phase 1 studies and is currently in Phase 2 testing. An initial Phase 1 study in normal healthy volunteers demonstrated rapid absorption, excellent exposure, and a half life consistent with once-daily dosing of MBX-2982. The second and third Phase 1 studies (multiple ascending dose trials in pre-diabetic subjects) examined MBX-2982 pharmacokinetics and glucose excursion effects following a mixed meal, using two alternate formulations. In both studies, MBX-2982 was rapidly absorbed and showed a statistically significant reduction in glucose excursions. In all studies to date, MBX-2982 was safe and generally well tolerated with no serious adverse events, adverse event trends or dose-limiting toxicities. These results provide clinical validation for the potential therapeutic benefits of MBX-2982 as a type 2 diabetes treatment.
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| The stimulation of GLP-1 release may mimic the benefits of incretin analogues such as exenatide (a GLP-1 analogue marketed as Byetta®). Unlike exenatide, however, MBX-2982 can be delivered orally. In addition, MBX-2982 may provide additional benefit when used in combination with a DPP-4 inhibitor such as sitagliptin (Januvia®), or other oral therapies. |
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| Other follow-on compounds for GPR119 are actively being developed. |
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