# Optimizing the Safety of the Newer Diabetes Medications in Patients with Diabetes and Kidney Disease

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $778,487

## Abstract

Sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-
1RA) are rapidly changing the therapeutic landscape for patients with diabetes and kidney disease, but are
underutilized in high-risk populations. Randomized controlled trials (RCTs) have robustly demonstrated the
cardiovascular and renoprotective benefits of these agents. For the first time in decades, we have new drugs to
slow kidney disease progression, yet newer medication classes are still underprescribed in patients with DKD.
One of the major prescribing barriers is the lack of safety data in real-world patients with DKD, a
complex, older population with multimorbidity and polypharmacy, who are at greater risk for adverse events
and drug-drug interactions (DDIs), but who are underrepresented or excluded from RCTs. This dearth of safety
data cannot be addressed by RCTs, since the RCTs were powered for effectiveness, not safety, did not
represent real-world patients with DKD who are an older, frailer population, and did not address DDIs in this
population with a high burden of polypharmacy. Yet, over time, these drugs should and will be prescribed to a
broader spectrum of patients with DKD. Methodologically rigorous studies using large, national healthcare
databases are an ideal vehicle to address these knowledge gaps with much larger sample sizes than in RCTs
across the broad spectrum of patients with DKD. Our overarching goal is to develop a framework to optimize
the safety of newer diabetes medications in real-world patients with DKD. We will investigate kidney-related
and other safety outcomes that were not systematically evaluated in RCTs in patients with DKD, using a new-
user, active comparator cohort approach (Aim 1). We will develop two safety monitoring approaches to assess
both anticipated and unanticipated adverse event signals associated with the newer diabetes medications as
they are used in real-world patients with DKD (Aim 2). Patients with DKD are at higher risk for DDIs since they
are older with impaired kidney function and have more multimorbidity and polypharmacy. We propose a novel
two-stage screening approach to detect and evaluate clinically relevant drug-drug interactions that could affect
the safety profile of newer diabetes medications in patients with DKD (Aim 3). This proposal will advance our
understanding of these drugs’ safety and, thus, will help overcome barriers to prescribing in patients with DKD
who may largely benefit from them. The filling of critical knowledge gaps and new insights regarding safe
prescribing will significantly influence the clinical management of patients with DKD.

## Key facts

- **NIH application ID:** 10799382
- **Project number:** 1R01DK135706-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Julie Paik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $778,487
- **Award type:** 1
- **Project period:** 2024-04-19 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799382

## Citation

> US National Institutes of Health, RePORTER application 10799382, Optimizing the Safety of the Newer Diabetes Medications in Patients with Diabetes and Kidney Disease (1R01DK135706-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10799382. Licensed CC0.

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