Table 1.

Challenges to drug development in type 2 diabetes

Unclear heterogeneity of the disease

Type 2 diabetes is used as a “catch-all” diagnosis.

Metabolic state changes with disease progression.

Disease subclassification is not routine in clinical practice.

Molecular pathogenesis is not fully elucidated.

Cost of drug development

Comparison with standard of care requires larger studies to demonstrate clinical benefit.

Proof of cardiovascular safety demands costly and complex trials.

Impact on diabetes complications takes too long to achieve.

The multiplicity of available pharmacological options constrains the therapeutic niche for novel agents, undermining viability.

Inadequacy of current practices

Preclinical models may not be relevant to the human situation.

Modulating glycemia may not be the critical end point.

Emergence of side effects in humans threatens new agents, as hyperglycemia does not confer immediate serious risk and can be controlled via other means. Initial evaluation of these side effects in phase 1 and 2 trials may be inefficient, insufficient, and expensive.