Should treatment with Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) be delayed in patients with Hemoglobin A1c (HbA1c) levels above 11%?

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From the Guidelines

It is not recommended to wait before starting an SGLT2 inhibitor (SGLT2i) if a patient's A1c is above 11%, as the most recent evidence suggests that SGLT2 inhibitors can be safely added to other antihyperglycemic medications when glycemic targets are not met, regardless of the initial A1c level. According to the 2025 standards of care in diabetes, treatment intensification, deintensification, or modification, as appropriate, for people not meeting individualized treatment goals should not be delayed 1. The 2021 guideline on diabetes management in chronic kidney disease also supports the use of SGLT2 inhibitors in patients with high A1c levels, as they provide significant cardiovascular and renal benefits, modest weight loss, and additional glucose control 1.

Key Considerations

  • SGLT2 inhibitors can be added to other antihyperglycemic medications when glycemic targets are not met, regardless of the initial A1c level 1
  • The cardiovascular and kidney benefits of SGLT2 inhibitors are seen across all categories of albuminuria and CKD, despite reduced glucose-lowering efficacy at lower eGFR 1
  • Patients initiating SGLT2 inhibitors should be educated on potential adverse effects, including modest volume contraction, blood pressure reduction, and weight loss 1

Treatment Approach

  • SGLT2 inhibitors like empagliflozin, dapagliflozin, or canagliflozin can be safely added to the treatment regimen, even in patients with high A1c levels
  • Insulin therapy may still be necessary to rapidly lower blood glucose levels, but SGLT2 inhibitors can provide additional benefits once glucose levels have improved and stabilized
  • The choice of treatment should be individualized, taking into account the patient's specific needs and medical history, as well as the potential risks and benefits of each medication 1

From the Research

SGLT2i Initiation with High A1c Levels

  • The decision to initiate SGLT2i treatment in patients with A1c levels above 11 should be based on individual patient needs and circumstances, as there is no straightforward answer to this question.
  • According to the study 2, insulin is often considered the preferred treatment for patients with type 2 diabetes and HbA1c levels exceeding 9%, but this may not always be the case.
  • The study 2 also suggests that GLP-1 receptor agonists may offer superior benefits to insulin in terms of HbA1c reduction, particularly in patients with higher baseline HbA1c levels.
  • Another study 3 found that the combination of a GLP-1 agonist and an SGLT2 inhibitor has additive effects on lowering HbA1c and systolic blood pressure, and may also reduce cardiovascular events and renal decompensation.
  • However, the study 4 recommends that insulin therapy be considered for patients with type 2 diabetes and HbA1c levels ≥ 10%, especially when diet, physical activity, and other antihyperglycemic agents have been optimally used.

Considerations for SGLT2i Treatment

  • The study 5 discusses the management of patients with type 2 diabetes and high A1c levels, and suggests that treatment intensification, including the use of GLP-1 receptor agonists and SGLT2 inhibitors, may be necessary to achieve glycemic control.
  • The study 6 reviews the efficacy and safety of GLP-1 receptor agonists, including their use in combination with SGLT2 inhibitors, and found that they are effective in lowering HbA1c and weight, with a low risk of hypoglycemia.
  • The study 3 highlights the potential benefits of combining SGLT2 inhibitors with GLP-1 receptor agonists, including improved glycemic control and reduced cardiovascular risk.
  • Ultimately, the decision to initiate SGLT2i treatment in patients with high A1c levels should be based on a comprehensive assessment of the patient's individual needs and circumstances, taking into account factors such as the presence of cardiovascular or renal disease, and the potential benefits and risks of treatment 3, 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Combination Treatment of SGLT2 Inhibitors and GLP-1 Receptor Agonists: Symbiotic Effects on Metabolism and Cardiorenal Risk.

Diabetes therapy : research, treatment and education of diabetes and related disorders, 2018

Research

EADSG Guidelines: Insulin Therapy in Diabetes.

Diabetes therapy : research, treatment and education of diabetes and related disorders, 2018

Research

Management of the T2D Patient With High A1C.

The Journal of family practice, 2019

Research

GLP-1 receptor agonists: an updated review of head-to-head clinical studies.

Therapeutic advances in endocrinology and metabolism, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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