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For adults with osteoporosis, how would Abaloparatide compare with an appropriate control on fractures and serious adverse events over two years?

A preregistered, independently replicated controlled study in adults with osteoporosis, measuring fractures and serious adverse events over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults undertaking exercise, how would Beta-alanine compare with an appropriate control on reproducible exercise performance over six months?

A preregistered, independently replicated controlled study in adults undertaking exercise, measuring reproducible exercise performance over six months, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would Bimagrumab compare with an appropriate control on physical function alongside body composition over one year?

A preregistered, independently replicated controlled study in adults with obesity, measuring physical function alongside body composition over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with musculoskeletal injury, how would BPC-157 compare with an appropriate control on validated recovery and serious adverse events over six months?

A preregistered, independently replicated controlled study in adults with musculoskeletal injury, measuring validated recovery and serious adverse events over six months, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults undertaking exercise, how would Caffeine compare with an appropriate control on performance alongside sleep and adverse effects over three months?

A preregistered, independently replicated controlled study in adults undertaking exercise, measuring performance alongside sleep and adverse effects over three months, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would Cagrilintide compare with an appropriate control on weight-related health outcomes over one year?

A preregistered, independently replicated controlled study in adults with obesity, measuring weight-related health outcomes over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would CagriSema compare with an appropriate control on weight-related health outcomes versus its individual components over one year?

A preregistered, independently replicated controlled study in adults with obesity, measuring weight-related health outcomes versus its individual components over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with diabetic kidney disease, how would Canagliflozin compare with an appropriate control on kidney failure and cardiovascular outcomes over two years?

A preregistered, independently replicated controlled study in adults with diabetic kidney disease, measuring kidney failure and cardiovascular outcomes over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults after cancer treatment, how would Circulating Tumor DNA compare with an appropriate control on survival when used to guide care over three years?

A preregistered, independently replicated controlled study in adults after cancer treatment, measuring survival when used to guide care over three years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults without diabetes, how would Continuous Glucose Monitoring compare with an appropriate control on patient-important health outcomes over one year?

A preregistered, independently replicated controlled study in adults without diabetes, measuring patient-important health outcomes over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults undertaking resistance training, how would Creatine compare with an appropriate control on physical function and falls over one year?

A preregistered, independently replicated controlled study in older adults undertaking resistance training, measuring physical function and falls over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with chronic kidney disease, how would Dapagliflozin compare with an appropriate control on kidney failure and mortality over two years?

A preregistered, independently replicated controlled study in adults with chronic kidney disease, measuring kidney failure and mortality over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults in senolytic research, how would Dasatinib compare with an appropriate control on physical function and serious adverse events over one year?

A preregistered, independently replicated controlled study in older adults in senolytic research, measuring physical function and serious adverse events over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would DNA Methylation compare with an appropriate control on prediction of functional health beyond standard risk factors over five years?

A preregistered, independently replicated controlled study in older adults, measuring prediction of functional health beyond standard risk factors over five years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with type 2 diabetes, how would Dulaglutide compare with an appropriate control on cardiovascular outcomes over two years?

A preregistered, independently replicated controlled study in adults with type 2 diabetes, measuring cardiovascular outcomes over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For people with inherited mitochondrial disease, how would Elamipretide compare with an appropriate control on physical function and serious adverse events over one year?

A preregistered, independently replicated controlled study in people with inherited mitochondrial disease, measuring physical function and serious adverse events over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with heart failure, how would Empagliflozin compare with an appropriate control on hospitalization and mortality over two years?

A preregistered, independently replicated controlled study in adults with heart failure, measuring hospitalization and mortality over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with muscle wasting, how would Enobosarm compare with an appropriate control on physical function and serious adverse events over one year?

A preregistered, independently replicated controlled study in adults with muscle wasting, measuring physical function and serious adverse events over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would Everolimus compare with an appropriate control on infection-related clinical outcomes and serious adverse events over one year?

A preregistered, independently replicated controlled study in older adults, measuring infection-related clinical outcomes and serious adverse events over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with type 2 diabetes, how would Exenatide compare with an appropriate control on cardiovascular outcomes over two years?

A preregistered, independently replicated controlled study in adults with type 2 diabetes, measuring cardiovascular outcomes over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would Fisetin compare with an appropriate control on physical function and serious adverse events over one year?

A preregistered, independently replicated controlled study in older adults, measuring physical function and serious adverse events over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity and obstructive sleep apnea, how would GLP-1 medicines for sleep apnea compare with an appropriate control on sleep apnea severity over one year?

A preregistered, independently replicated controlled study in adults with obesity and obstructive sleep apnea, measuring sleep apnea severity over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would Ibutamoren compare with an appropriate control on physical function and metabolic safety over one year?

A preregistered, independently replicated controlled study in older adults, measuring physical function and metabolic safety over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults in postoperative recovery, how would Ipamorelin compare with an appropriate control on recovery of bowel function and serious adverse events over one month?

A preregistered, independently replicated controlled study in adults in postoperative recovery, measuring recovery of bowel function and serious adverse events over one month, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults undertaking exercise, how would L-Citrulline compare with an appropriate control on reproducible exercise performance over six months?

A preregistered, independently replicated controlled study in adults undertaking exercise, measuring reproducible exercise performance over six months, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For asymptomatic adults, how would Liquid Biopsy compare with an appropriate control on cancer mortality and harms from follow-up procedures over five years?

A preregistered, independently replicated controlled study in asymptomatic adults, measuring cancer mortality and harms from follow-up procedures over five years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would Liraglutide compare with an appropriate control on maintenance of weight-related health benefits over two years?

A preregistered, independently replicated controlled study in adults with obesity, measuring maintenance of weight-related health benefits over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with type 2 diabetes, how would Lixisenatide compare with an appropriate control on cardiovascular outcomes over two years?

A preregistered, independently replicated controlled study in adults with type 2 diabetes, measuring cardiovascular outcomes over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would Mazdutide compare with an appropriate control on weight-related health outcomes over one year?

A preregistered, independently replicated controlled study in adults with obesity, measuring weight-related health outcomes over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults without diabetes, how would Metformin compare with an appropriate control on healthy lifespan and functional outcomes over five years?

A preregistered, independently replicated controlled study in adults without diabetes, measuring healthy lifespan and functional outcomes over five years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with metabolic dysfunction, how would MOTS-c compare with an appropriate control on validated metabolic and functional outcomes over one year?

A preregistered, independently replicated controlled study in adults with metabolic dysfunction, measuring validated metabolic and functional outcomes over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would Nicotinamide mononucleotide compare with an appropriate control on physical function and serious adverse events over one year?

A preregistered, independently replicated controlled study in older adults, measuring physical function and serious adverse events over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would Nicotinamide riboside compare with an appropriate control on physical function and serious adverse events over one year?

A preregistered, independently replicated controlled study in older adults, measuring physical function and serious adverse events over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would Orforglipron compare with an appropriate control on weight-related health outcomes over one year?

A preregistered, independently replicated controlled study in adults with obesity, measuring weight-related health outcomes over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with metabolic liver disease, how would Pemvidutide compare with an appropriate control on liver-related clinical outcomes over two years?

A preregistered, independently replicated controlled study in adults with metabolic liver disease, measuring liver-related clinical outcomes over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with metabolic dysfunction, how would Resveratrol compare with an appropriate control on validated metabolic health outcomes over one year?

A preregistered, independently replicated controlled study in adults with metabolic dysfunction, measuring validated metabolic health outcomes over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would Retatrutide compare with an appropriate control on weight-related health outcomes and serious adverse events over one year?

A preregistered, independently replicated controlled study in adults with obesity, measuring weight-related health outcomes and serious adverse events over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would Semaglutide compare with an appropriate control on cardiovascular events over at least two years?

A preregistered, independently replicated controlled study in adults with obesity, measuring cardiovascular events over at least two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For people with genetically defined obesity, how would Setmelanotide compare with an appropriate control on sustained hunger and health outcomes over one year?

A preregistered, independently replicated controlled study in people with genetically defined obesity, measuring sustained hunger and health outcomes over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults without a transplant indication, how would Sirolimus compare with an appropriate control on functional health and serious infections over two years?

A preregistered, independently replicated controlled study in older adults without a transplant indication, measuring functional health and serious infections over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with heart failure, how would Sotagliflozin compare with an appropriate control on hospitalization and mortality over two years?

A preregistered, independently replicated controlled study in adults with heart failure, measuring hospitalization and mortality over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would Spermidine compare with an appropriate control on cognitive function over two years?

A preregistered, independently replicated controlled study in older adults, measuring cognitive function over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with metabolic liver disease, how would Survodutide compare with an appropriate control on liver-related clinical outcomes over two years?

A preregistered, independently replicated controlled study in adults with metabolic liver disease, measuring liver-related clinical outcomes over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would Taurine compare with an appropriate control on physical function and cardiometabolic outcomes over one year?

A preregistered, independently replicated controlled study in older adults, measuring physical function and cardiometabolic outcomes over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with osteoporosis, how would Teriparatide compare with an appropriate control on fractures and serious adverse events over two years?

A preregistered, independently replicated controlled study in adults with osteoporosis, measuring fractures and serious adverse events over two years, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with HIV-associated lipodystrophy, how would Tesamorelin compare with an appropriate control on health outcomes alongside body composition over one year?

A preregistered, independently replicated controlled study in adults with HIV-associated lipodystrophy, measuring health outcomes alongside body composition over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with severe infection, how would Thymosin alpha 1 compare with an appropriate control on mortality and serious adverse events over three months?

A preregistered, independently replicated controlled study in adults with severe infection, measuring mortality and serious adverse events over three months, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with tissue injury, how would Thymosin beta 4 compare with an appropriate control on validated healing and functional outcomes over six months?

A preregistered, independently replicated controlled study in adults with tissue injury, measuring validated healing and functional outcomes over six months, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For adults with obesity, how would Tirzepatide compare with an appropriate control on weight-related health outcomes over at least one year?

A preregistered, independently replicated controlled study in adults with obesity, measuring weight-related health outcomes over at least one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.

For older adults, how would Urolithin A compare with an appropriate control on physical function over one year?

A preregistered, independently replicated controlled study in older adults, measuring physical function over one year, with complete adverse-event reporting and a clinically meaningful between-group result would support reassessment. A credible null result or serious harm would also require reassessment.