TTP399: an investigational liver-selective glucokinase (GK) activator as a potential treatment for type 2 diabetes

ABSTRACT

Introduction: Type 2 diabetes is a complex metabolic disorder defined by hyperglycemia which occurs because of impaired insulin secretion and sensitivity. There is an ongoing need to develop novel therapies that are effective and safe with minimal side effects and long-term durability. TTP399 is a hepatoselective, glucokinase activator with potential for treating type 2 diabetes.

Areas covered: This is a review of the available data regarding the mechanism of action and the pharmacokinetics of TTP399. The efficacy and safety of the drug for treatment of type 2 diabetes will also be examined with an emphasis on the results of a randomized, controlled phase 2 study.

Expert opinion: TTP399 could offer significant advantages over currently available therapies for type 2 diabetes. It successfully lowers glucose without side effects such as hypoglycemia, weight gain or dyslipidemia. Larger trials are required to understand long-term efficacy and safety of this medication in various patient populations and to elucidate its effect on the pathologic processes underpinning type 2 diabetes.

KEYWORDS:

• Glucokinase activator
• type 2 diabetes
• TTP399
• glucose metabolism

Article Highlights

• Glucokinase is an important therapeutic target in Type 2 Diabetes.

• To date compounds targeting this enzyme have produced disappointing results due to hypoglycemia and other adverse events.

• Selectivity for hepatic glucokinase may confer therapeutic benefit.

Declaration of interest

AVella was a VTv Therapeutics LLC Advisory Board Member and lead investigator of the AGATA trial. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Additional information

Funding

This paper was not funded.