Potential Effects of Metformin on Aging and Age-Related Conditions: Small-Scale Clinical Studies and Secondary Analysis of Controlled Clinical Studies (R01 Clinical Trial Optional) | PA 18 025

Frequently Asked Questions (FAQs)

What is the purpose of NIH funding opportunity PA-18-025?

PA-18-025 supports NIH R01 applications that test whether metformin (a widely used diabetes medication) has clinically meaningful effects on aging biology and age-related conditions beyond its established antihyperglycemic role. The focus is on human, translational evidence that can clarify whether metformin could delay harmful age-related changes, reduce risk for age-associated diseases, or extend healthspan.

Why is metformin being studied in the context of aging?

The opportunity is based on hints from multiple clinical studies across different patient groups suggesting metformin may influence physiologic pathways relevant to aging. NIH is seeking research that moves beyond suggestive associations toward clearer, mechanism-informed evidence in humans.

What grant mechanism is used for this opportunity?

The mechanism is an NIH R01 research project grant.

Is a clinical trial required under this FOA?

No. The FOA is designated “Clinical Trial Optional.” Applicants may propose a clinical trial if it fits the scientific aims, but a clinical trial is not required.

What kinds of projects does the FOA prioritize?

The FOA is designed around two main project types: (1) small-scale physiologic studies in humans and (2) secondary analyses of existing data and/or stored biospecimens from controlled clinical intervention studies involving metformin.

What is meant by “small-scale physiologic studies in humans” in this announcement?

These are carefully controlled human studies intended to measure metformin-related changes in human physiology, functional outcomes, or biomarkers linked to aging processes. They are not positioned as large, definitive clinical endpoint trials; instead, they aim to produce strong mechanistic or translational evidence at a practical, relatively small scale.

Are large clinical endpoint trials the main goal of this FOA?

No. The opportunity emphasizes controlled, mechanistically informative human evidence rather than large, definitive trials designed primarily around major clinical endpoints.

What does “secondary analysis” mean for this funding opportunity?

Secondary analysis refers to using existing datasets and/or stored biospecimens from controlled clinical intervention studies to ask new questions relevant to aging. Examples described include reanalyzing data from prior randomized controlled trials or other controlled interventions where metformin was used, and testing banked samples for cellular or molecular markers that were not part of the original primary outcomes.

Do projects need to generate new data, or can they use existing resources?

Both approaches are supported. Applicants may propose new small-scale controlled human studies, or they may conduct rigorous secondary analyses using existing controlled-study data and/or stored biospecimens.

What kinds of outcomes or measurements are encouraged?

The FOA highlights measurements of human physiology, functional outcomes, and biomarkers linked to aging processes, as well as cellular or molecular markers measurable in stored biospecimens. The overall intent is to understand metformin’s effects on human biology in ways that could plausibly matter for aging and age-related decline.

Does the FOA focus on identifying who benefits most from metformin?

Yes. A central goal is to identify which populations may be most likely to benefit from metformin in the context of aging and age-related conditions.

Does NIH want researchers to treat “older adults” as a single uniform group?

No. The announcement explicitly encourages examining subgroup differences rather than treating older adults as a homogeneous population.

What kinds of subgroup or population characteristics are of interest?

The FOA encourages analyses of subgroup differences, risk profiles, comorbidities, baseline metabolic status, and other characteristics that might predict response to metformin or change the risk-benefit balance.

Is the research expected to be translational?

Yes. The emphasis is on translational aging research with controlled human evidence, designed to clarify effects of metformin on aging biology and age-related conditions.

What is NIH hoping to learn about metformin’s mechanisms in humans?

NIH is interested in clarifying metformin’s physiologic and cellular effects in humans, particularly effects that could reveal new molecular targets relevant to aging biology.

If metformin is not ultimately the best intervention for aging, is this research still valuable?

Yes. The FOA notes that even if metformin itself is not the best long-term intervention, understanding what it does in people could reveal pathways and targets for future therapeutics.

What type of federal assistance category is associated with this opportunity?

The opportunity is categorized under education and health-related federal assistance.

What CFDA numbers are associated with this FOA?

The FOA is associated with CFDA numbers 93.393 and 93.866.

Who is eligible to apply?

Eligibility is broad and includes many organization types that can hold NIH grants, including: state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses.

Are any additional organization categories explicitly highlighted as eligible?

Yes. The FOA explicitly highlights additional eligible categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, regional organizations, and non-U.S. (foreign) entities.

Are non-U.S. (foreign) entities eligible?

Yes. Non-U.S. (foreign) entities are listed among eligible applicants.

Does the excerpt specify an award ceiling or number of expected awards?

No. The provided listing excerpt does not specify an award ceiling or the expected number of awards.

Where should applicants look for budget expectations or institute-specific priorities?

Because the excerpt does not provide budget expectations, receipt dates, or institute-specific priorities, applicants would typically consult the full NIH announcement and any related institute guidance for those details.

When was this opportunity created, and what closing date is shown in the source information?

The administrative details shown indicate the opportunity was created on 2017-11-01 and lists an original closing date of 2020-05-07 (reflecting the historical posting information provided).

What is the overall emphasis of PA-18-025 in one sentence?

It is a targeted call for controlled, human-focused translational aging research to clarify whether metformin meaningfully influences aging biology, identify who might benefit most, and extract actionable molecular insights from its effects in people.