Science's open questions, ranked.

Each comes with the experiment that would settle it.

159OpenThe evidence has not settled it
126ClosingOf the open ones, a trial is under way
20SettledReplicated or established
3,881Trials placedRegistered trials behind these questions
Bench loop prototypeFrom an open question to a lab result, in one loop.Mechanistic modelGaps it can't explainExperiments, arguedYour approvalLab runModel updatesTry it on metformin and liver fat →

Most worth testing next

Ranked by how much the next trial would change what we believe, weighted by what's at stake and what it costs.

  1. 01
    Do sulfonylureas & glinides improve cardiac & vascular function more than other treatments?

    Type 2 & unspecified diabetes

    Opendoubtful

    Would settle itRandomized trial · mechanistic or pharmacology study

    So far: no trial evidence yet

  2. 02
    Does metformin improve liver & MASLD versus placebo?

    Type 2 & unspecified diabetes

    Bench loop: model the mechanism and run the experiment →
    Closinga coin flip

    Would settle itRandomized trial · surrogate-endpoint trial · 19 trials under way

    So far: one result, not yet repeated

  3. 03
    Do sulfonylureas & glinides improve lipids versus placebo?

    Type 2 & unspecified diabetes

    Opena coin flip

    Would settle itRandomized trial · surrogate-endpoint trial

    So far: one result, not yet repeated

  4. 04
    Do statins improve body weight & composition more than other treatments?

    Obesity & overweight

    Closinga coin flip

    Would settle itRandomized trial · surrogate-endpoint trial · 7 trials under way

    So far: one result, not yet repeated

  5. 05
    Does metformin improve blood pressure more than other treatments?

    Type 2 & unspecified diabetes

    Closinga coin flip

    Would settle itRandomized trial · surrogate-endpoint trial · 22 trials under way

    So far: one result, not yet repeated

  6. 06
    Do anti-obesity drugs improve blood pressure versus placebo?

    Obesity & overweight

    Opendoubtful

    Would settle itRandomized trial · surrogate-endpoint trial

    So far: no trial evidence yet

  7. 07
    Do statins improve liver & MASLD more than other treatments?

    Coronary & atherosclerotic disease

    Closingdoubtful

    Would settle itRandomized trial · surrogate-endpoint trial · 19 trials under way

    So far: no trial evidence yet

  8. 08
    Do statins improve body weight & composition versus placebo?

    Obesity & overweight

    Closingdoubtful

    Would settle itRandomized trial · surrogate-endpoint trial · 7 trials under way

    So far: no trial evidence yet

  9. 08
    Do diet, exercise & lifestyle improve liver & MASLD versus placebo?

    Obesity & overweight

    Closinga coin flip

    Would settle itRandomized trial · surrogate-endpoint trial · 14 trials under way

    So far: one result, not yet repeated

  10. 09
    Do investigational compounds improve liver & MASLD more than other treatments?

    Type 2 & unspecified diabetes

    Closinga coin flip

    Would settle itRandomized trial · surrogate-endpoint trial · 5 trials under way

    So far: one result, not yet repeated