Symbolic representation of the amputation risk associated with diabetes medication.

SGLT2 Inhibitors and Amputation Risk: What You Need to Know About Diabetes Medication Safety

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Mira Elwood in Health & Wellness November 2025 • 4 min read.

"New research links a common class of diabetes drugs to an increased risk of lower limb amputation. Learn about the potential risks and what this means for your health."


For individuals managing type 2 diabetes, maintaining a delicate balance between effective treatment and potential side effects is crucial. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become increasingly popular for their ability to lower blood sugar levels. However, a recent study published in The BMJ has raised concerns about a potential link between these medications and an elevated risk of lower limb amputation and diabetic ketoacidosis when compared to glucagon-like peptide 1 (GLP1) receptor agonists.

SGLT2 inhibitors work by preventing the kidneys from reabsorbing glucose back into the blood, which results in excess glucose being excreted through urine. While effective at managing blood sugar, this mechanism may also carry unintended consequences. Understanding these potential risks is vital for both patients and healthcare providers.

This article aims to break down the key findings of the study, explore the implications for individuals with diabetes, and provide actionable information to help you make informed decisions about your treatment plan.

Understanding the Study: Linking SGLT2 Inhibitors and Amputation Risk

Symbolic representation of the amputation risk associated with diabetes medication.

An international research team analyzed data from Sweden and Denmark, focusing on 17,213 patients who initiated SGLT2 inhibitors and another 17,213 patients who began taking GLP1 receptor agonists between July 2003 and December 2016. The participants, all over the age of 35, had no prior prescriptions for either drug class and no history of severe kidney problems or pancreatic disorders.

The study tracked several outcomes, including lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis. After accounting for numerous factors such as disease history, other medications, and socioeconomic indicators, the researchers found a significant association:

  • Increased Amputation Risk: SGLT2 inhibitors were linked to a twofold increase in the risk of lower limb amputation (2.7 vs 1.1 events per 1000 person years; hazard ratio 2.32 (95% confidence interval 1.37 to 3.91)).
  • Elevated Ketoacidosis Risk: The study also showed a higher risk of diabetic ketoacidosis (1.3 ν 0.6; 2.14 (1.01 to 4.52)) compared to GLP1 receptor agonists.
  • No Significant Increase in Other Risks: Interestingly, the study did not find a significant increase in the risk of bone fracture, acute kidney injury, serious urinary tract infection, venous thromboembolism, or acute pancreatitis.
While the study highlights potential risks, it's important to acknowledge its limitations. The observational nature of the research means that the scientists cannot definitively establish a cause-and-effect relationship. Unmeasured factors could have influenced the results. Additionally, the study looked at SGLT2 inhibitors as a class rather than as individual drugs, which means that certain medications within the class may pose a higher or lower risk.

Making Informed Decisions: What This Means for You

If you are currently taking an SGLT2 inhibitor, it is essential to have an open and honest conversation with your healthcare provider. Do not stop taking your medication without consulting your doctor, as this could lead to dangerous fluctuations in your blood sugar levels. Instead, discuss your concerns, review the potential risks and benefits of your current treatment plan, and explore alternative options if necessary. Regular foot exams and proactive management of any existing risk factors are crucial for minimizing potential complications.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1136/bmj.k4828, Alternate LINK

Title: Sglt2 Inhibitors For Diabetes Are Linked To Increased Risk Of Lower Limb Amputation

Subject: General Engineering

Journal: BMJ

Publisher: BMJ

Authors: Zosia Kmietowicz

Published: 2018-11-14

Everything You Need To Know

1

What are SGLT2 inhibitors, and how do they work?

SGLT2 inhibitors are a class of medications used to treat type 2 diabetes. They work by preventing the kidneys from reabsorbing glucose back into the blood. As a result, excess glucose is excreted through urine, which helps lower blood sugar levels. However, this mechanism can also carry unintended consequences, as highlighted by recent research.

2

What are the key findings of the study regarding SGLT2 inhibitors and amputation risk?

The study revealed a significant association between SGLT2 inhibitors and an increased risk of lower limb amputation. Specifically, the research showed a twofold increase in amputation risk for patients taking SGLT2 inhibitors compared to those taking GLP1 receptor agonists. The study also indicated a higher risk of diabetic ketoacidosis with SGLT2 inhibitors.

3

How does the risk of lower limb amputation compare between SGLT2 inhibitors and GLP1 receptor agonists?

The study found that patients taking SGLT2 inhibitors had a significantly higher risk of lower limb amputation compared to those taking GLP1 receptor agonists. The hazard ratio was 2.32, indicating that SGLT2 inhibitors were linked to a more than double the risk of amputation compared to GLP1 receptor agonists. The study reported 2.7 events per 1000 person years for SGLT2 inhibitors versus 1.1 events per 1000 person years.

4

Besides amputation risk, what other health risks were associated with SGLT2 inhibitors in the study?

In addition to the increased risk of lower limb amputation, the study also found a higher risk of diabetic ketoacidosis among patients taking SGLT2 inhibitors. There was no significant increase in the risk of bone fracture, acute kidney injury, serious urinary tract infection, venous thromboembolism, or acute pancreatitis observed in the study.

5

If I'm taking an SGLT2 inhibitor, what steps should I take in light of this research?

If you are currently taking an SGLT2 inhibitor, it is essential to have an open and honest conversation with your healthcare provider. Do not stop taking your medication without consulting your doctor. Discuss your concerns, review the potential risks and benefits of your current treatment plan, and explore alternative options if necessary. Also, regular foot exams and proactive management of any existing risk factors are crucial for minimizing potential complications.

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