Type 2 diabetes — GSK-3 beta

GSK-3 beta inhibition would reduce tau hyperphosphorylation and slow decline in mild-to-moderate Alzheimer's.

CSF p-tau181 dropped by 28% but ADAS-Cog showed no difference from placebo; the high-dose arm was halted for safety.

Why it matched: shares GSK3B · shared focus: GSK-3 beta · similar wording

GPR40 agonism would boost glucose-stimulated insulin secretion without the hypoglycemia risk of sulfonylureas.

Efficacy was strong in rodent models but did not replicate in primate islet studies.

Why it matched: same research area · similar wording · mechanism: Metabolic & insulin signalling · failed the same way: Held in the model species, not beyond it

Twelve weeks of endurance exercise, vitamin D, or both would reduce insulin resistance (HOMA-IR) in middle-aged adults with type 2 diabetes.

Across 61 participants randomised to control, exercise, vitamin D or both, none of the interventions improved HOMA-IR, the primary outcome; only fasting glucose fell in the combined group (−11.9%).

Why it matched: same research area · mechanism: Metabolic & insulin signalling

Mice lacking the GPR21 receptor would resist diet-induced obesity and have better glucose tolerance, as an earlier knockout line showed.

A new GPR21 knockout line made with TALEN gene editing did not keep the better metabolic profile on a normal or high-fat diet.

Why it matched: mechanism: Metabolic & insulin signalling · failed the same way: Held in the model species, not beyond it