Continuous Ketone Monitoring for the Safe Use of Sodium-glucose Cotransporter-2 Inhibitors in Type 1 Diabetes (R01 Clinical trial Required) | RFA DK 23 011

Opportunity Information: Apply for RFA DK 23 011

This NIH grant opportunity (RFA-DK-23-011) supports R01 clinical trials that focus on making sodium-glucose cotransporter-2 inhibitors (SGLT2i) safer to use in people living with type 1 diabetes (T1D) by integrating continuous ketone monitoring (CKM) into real-world clinical care. SGLT2 inhibitors were originally developed for type 2 diabetes, but they have shown meaningful benefits beyond glucose lowering, including protection for the heart and kidneys in people with and without diabetes. Even so, SGLT2i are not currently approved for T1D because they can raise the risk of diabetic ketoacidosis (DKA), a serious and potentially life-threatening complication. Despite this regulatory and safety concern, the drugs are increasingly being used off-label in T1D, which creates an urgent need for practical risk-mitigation approaches that allow patients to benefit from these therapies while reducing DKA risk.

The central idea behind the funding announcement is that CKM, a newer and rapidly evolving technology, may provide early warning when ketone levels begin to rise, enabling timely intervention before a patient progresses to full DKA. The NOFO is therefore looking for short-term clinical trials that develop, refine, and test strategies for combining CKM with SGLT2i therapy in T1D. Projects should generate actionable evidence on safety (especially DKA prevention and early detection) while also examining glucose outcomes when SGLT2i are used with structured ketone surveillance and response plans. The expectation is not just to study CKM as a gadget, but to demonstrate how it can be integrated into clinical workflows, patient education, and treatment decision-making in a way that can be disseminated and adopted.

Examples of the kinds of research topics the NOFO highlights include evaluating how different insulin delivery approaches interact with SGLT2i and ketone dynamics. This can involve people using automated insulin delivery systems (closed-loop), more traditional pump therapy (open-loop), or multiple daily injections, with the goal of identifying insulin strategies that minimize ketone accumulation risk without losing the glycemic and potential cardio-renal advantages of SGLT2i. Another major theme is the creation and testing of clinical protocols for what to do when ketones rise, such as clear algorithms for additional insulin dosing, carbohydrate intake, hydration, temporary SGLT2i interruption, sick-day management, and thresholds for escalation to urgent evaluation. In other words, the research should move beyond observation and directly test risk-reduction playbooks that clinicians and patients can follow.

Administratively, this is a discretionary grant program run by the National Institutes of Health under the R01 mechanism, and it explicitly requires a clinical trial. The original application closing date listed is 2024-06-27. The opportunity lists an award ceiling of $500,000 and indicates expected awards will be made (the posted field shows "ExpectedAwards:" without a number, but it signals that NIH anticipates making awards). The assistance listing is under CFDA 93.847, and the activity category is health (also tagged food and nutrition, health), aligning it with diabetes and metabolic disease research priorities.

Eligibility is broad and includes many common NIH applicant categories: state, county, and local governments; public and private institutions of higher education; nonprofit organizations (both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses) as well as small businesses; independent school districts; special district governments; public housing authorities/Indian housing authorities; and Native American tribal governments (federally recognized) and tribal organizations (other than federally recognized governments). The announcement also emphasizes inclusion of a wide range of additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and even non-U.S. entities (foreign organizations), reflecting NIH interest in diverse institutional participation and potentially broader generalizability of findings.

Overall, the grant is aimed at a very practical clinical problem: SGLT2 inhibitors may offer meaningful benefits for people with T1D, but DKA risk has limited approval and safe uptake. By funding clinical trials that integrate continuous ketone monitoring with clear intervention protocols, the NIH is seeking evidence-based pathways that can reduce risk, improve safety monitoring, and guide clinicians on how to use (or potentially justify future use of) SGLT2i in T1D with stronger safeguards in place.

• The National Institutes of Health in the food and nutrition, health sector is offering a public funding opportunity titled "Continuous Ketone Monitoring for the Safe Use of Sodium-glucose Cotransporter-2 Inhibitors in Type 1 Diabetes (R01 Clinical trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.847.
• This funding opportunity was created on 2024-01-30.
• Applicants must submit their applications by 2024-06-27. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $500,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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