# Factors Associated with Response to SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Veterans with Type 2 Diabetes Mellitus

**Authors:** Gunjan Arora, Sulman Hashmi, Samson Kaeli, Sarah Azad, Jaskaran Batra, Vijaya Deepika Perugu, Clifton Davis, Cyrus V. Desouza

PMC · DOI: 10.3390/jcm14124092 · 2025-06-10

## TL;DR

This study identifies factors that predict which Veterans with type 2 diabetes will respond well to SGLT-2 inhibitors or GLP-1 receptor agonists.

## Contribution

The study provides insights into baseline characteristics associated with treatment response to SGLT-2i and GLP-1 RA in Veterans with T2DM.

## Key findings

- Patients on GLP-1 RA had higher odds of adequate response compared to those on SGLT-2i.
- Higher baseline HbA1c and older age were significantly associated with better treatment outcomes.
- Achieving both HbA1c and weight reduction defined adequate responders.

## Abstract

Background: SGLT2 inhibitors (SGLT-2i) and GLP1 receptor agonists (GLP-1 RA) are recommended as the first line therapy for the management of type 2 diabetes mellitus (T2DM), particularly in patients with chronic kidney disease (CKD), cardiovascular disease (CVD), and heart failure (HF). Despite their established efficacy, there is limited evidence available to predict which subset of patients will respond favorably to them. We conducted this study to identify baseline characteristics to predict the response to therapy with SGLT-2i and GLP-1 RA. Methods: A retrospective analysis of the medical records was conducted at the Veteran Affairs Medical Center (VAMC) in Omaha, Nebraska, USA. Veterans who had completed 6–12 months of treatment with SGLT-2i or GLP-1 RA were included. Favorable treatment outcomes were a ≥0.5% reduction in glycosylated hemoglobin (HbA1c) or a ≥5% reduction in body weight; and those who achieved both outcomes were classified as adequate responders. Results: Patients in the GLP-1 RA group had 2.11 (95% CI: 1.45, 3.07) times the odds of achieving an adequate response as compared to patients in the SGLT-2i group in the unadjusted analysis, p < 0.001. HbA1c > 8% and older age was significantly associated with achieving an adequate response. Conclusions: Treatment with GLP-1 RA should be considered in Veterans with these characteristics.

## Linked entities

- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), chronic kidney disease (MONDO:0005300), cardiovascular disease (MONDO:0004995), heart failure (MONDO:0005252)

## Full-text entities

- **Genes:** GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}
- **Diseases:** HF (MESH:D006333), CVD (MESH:D002318), T2DM (MESH:D003924), CKD (MESH:D051436)
- **Chemicals:** GLP-1 RA (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12194277/full.md

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Source: https://tomesphere.com/paper/PMC12194277