SGLT2 Inhibitors for Type 1 Diabetes: Pros, Cons, and Off-Label Use Explained

Author: Ariel Warren, RDN, LD ,CDCES

Hey there! Have you heard of SGLT2 inhibitors? They’re a type of medication typically used to treat type 2 diabetes, but there’s been a lot of talk about whether they could also be used for people with type 1 diabetes – even though it’s technically not approved by the FDA.

So, what are the pros and cons of using SGLT2 inhibitors for type 1 diabetes? Let’s break it down.

On the plus side, SGLT2 inhibitors have been shown to help lower blood glucose levels in people with type 1 diabetes. This could lead to better control of the condition and overall improved health. Plus, these drugs are associated with weight loss, which is great news for people with type 1 diabetes who may struggle with their weight. SGLT2 inhibitors may also reduce the amount of insulin needed to manage blood glucose levels, which could help lower the risk of hypoglycemia. And there’s even some evidence to suggest that SGLT2 inhibitors may have cardiovascular benefits, such as reducing the risk of heart failure and cardiovascular death.

But as with any medication, there are also some potential drawbacks to consider. One major concern is the increased risk of diabetic ketoacidosis (DKA), a serious condition that can be life-threatening. SGLT2 inhibitors can also increase the risk of genital and urinary infections, which can be particularly problematic for people with type 1 diabetes who are already at higher risk of infections. Additionally, these drugs can cause dehydration and low blood pressure, which can be especially dangerous for people with type 1 diabetes who may already be at risk of low blood pressure due to autonomic neuropathy. And perhaps the biggest downside is that there’s limited long-term data on the safety and efficacy of using SGLT2 inhibitors for type 1 diabetes, so it’s difficult to know for sure what the risks and benefits are.

Mechanism of Action for SGLT2 Inhibitors

SGLT2 inhibitors work by blocking a protein called sodium-glucose co-transporter 2 (SGLT2), which is responsible for reabsorbing glucose in the kidneys. By blocking this protein, SGLT2 inhibitors cause excess glucose to be excreted in the urine, which can help lower blood glucose levels.

In people with type 2 diabetes, SGLT2 inhibitors also help to improve insulin sensitivity and reduce insulin resistance. However, their exact mechanism of action in people with type 1 diabetes is not yet fully understood.

It’s important to note that while SGLT2 inhibitors can be effective in lowering blood glucose levels, they are not a cure for diabetes and should always be used in conjunction with other treatments and lifestyle modifications. As with any medication, it’s important to discuss the potential benefits and risks with your doctor before starting treatment.

While there may be some potential benefits to using SGLT2 inhibitors for type 1 diabetes, there are also some serious risks to consider. If you’re thinking about this off-label use, it’s important to talk to your healthcare provider and weigh the pros and cons before making any decisions.

So, what are the pros and cons of using SGLT2 inhibitors for type 1 diabetes? Let’s break it down by each individual drug. As of May 22, 2023, there are five FDA-approved SGLT2 inhibitors available: canagliflozin (Invokana), dapagliflozin (Farxiga), Steglatro (ertugliflozin), empagliflozin (Jardiance), and the most recent, bexagliflozin Brenzavvy).

Below are the pros and cons of each SGLT2 inhibitor for people with type 1 diabetes:

1. Canagliflozin (Invokana)

Pros:

• Improved glycemic control
• Weight loss
• Reduced risk of cardiovascular disease
• Lowered blood pressure

Cons:

• Increased risk of urinary tract infections and genital mycotic infections
• Increased risk of lower limb amputations
• Risk of dehydration and electrolyte imbalances
• Potential increase in bone fractures
• Increased risk of ketoacidosis

2. Dapagliflozin (Farxiga)

Pros:

• Improved glycemic control
• Weight loss
• Reduced risk of cardiovascular disease
• Lowered blood pressure

Cons:

• Increased risk of urinary tract infections and genital mycotic infections
• Increased risk of dehydration and electrolyte imbalances
• Increased risk of ketoacidosis

3. Steglatro (ertugliflozin)

Pros:

• Improved glycemic control
• Reduced risk of cardiovascular disease
• Lowered blood pressure

Cons:

• Increased risk of urinary tract infections and genital mycotic infections
• Increased risk of dehydration and electrolyte imbalances
• Potential increase in bone fractures
• Increased risk of ketoacidosis

4. Empagliflozin (Jardiance)

Pros:

• Improved glycemic control
• Reduced risk of cardiovascular disease
• Lowered blood pressure
• Potential reduction in all-cause mortality

Cons:

• Increased risk of urinary tract infections and genital mycotic infections
• Increased risk of dehydration and electrolyte imbalances
• Potential increase in bone fractures
• Increased risk of ketoacidosis

5. Bexagliflozin (Brenzavvy)

Pros:

• Improved glycemic control
• Reduced risk of cardiovascular disease
• Lowered blood pressure

Cons:

• Increased risk of urinary tract infections and genital mycotic infections
• Increased risk of dehydration and electrolyte imbalances
• Potential increase in bone fractures
• Increased risk of ketoacidosis

It’s important to note that the benefits and risks of SGLT2 inhibitors can vary depending on the individual, and should be discussed with a healthcare provider before starting treatment.

Key Points to Takeaway about SGLT2 Inhibitors:

• SGLT2 inhibitors are a type of medication used to treat type 2 diabetes, but some doctors are prescribing them off-label for people with type 1 diabetes to help manage blood glucose levels.
• The five SGLT2 inhibitors currently approved by the FDA for use in the United States are canagliflozin (Invokana), dapagliflozin (Farxiga), Steglatro (ertugliflozin), empagliflozin (Jardiance), and the most recent, bexagliflozin Brenzavvy).
• Each of these drugs has its own set of pros and cons, so it’s important to weigh the potential benefits against the risks and side effects before starting a new medication.
• Lifestyle changes, such as making dietary modifications and incorporating exercise into your routine, should always be the first line of defense for managing type 1 diabetes.
• If you’re considering an SGLT2 inhibitor, talk to your doctor about whether it might be a good option for you, and be sure to monitor your blood glucose levels and report any side effects or symptoms of DKA.
• Remember that managing type 1 diabetes is a complex and ongoing process, and what works for one person may not work for another. It’s important to work closely with your healthcare team to develop a personalized treatment plan that takes into account your individual needs and goals.

References:

1. American Diabetes Association. Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44(Suppl 1):S15-S33. doi:10.2337/dc21-S002.
2. American Diabetes Association. Living with Diabetes: Medications – SGLT2 inhibitors. https://www.diabetes.org/diabetes/medication-management/blood-glucose-lowering-medications/sodium-glucose-cotransporter-2-inhibitors. Accessed May 14, 2023.
3. National Institute of Diabetes and Digestive and Kidney Diseases. Type 1 Diabetes. https://www.niddk.nih.gov/health-information/diabetes/overview/type-1-diabetes. Accessed May 14, 2023.
4. National Institute of Diabetes and Digestive and Kidney Diseases. Type 2 Diabetes. https://www.niddk.nih.gov/health-information/diabetes/overview/type-2-diabetes. Accessed May 14, 2023.
5. Råstam J, Jönsson T, Lidfeldt J, Nerbrand C, Nilsson PM. Use of SGLT2 inhibitors in clinical practice: Effectiveness, safety, and perspectives. Endocrinol Diabetes Metab. 2022;5(2):e00237. doi:10.1002/edm2.237.
6. Rosenstock J, Ferrannini E. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors. Diabetes Care. 2015;38(9):1638-1642. doi:10.2337/dc15-1380.
7. US Food and Drug Administration. FDA approves new treatment for hospital-acquired and ventilator-associated bacterial pneumonia. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-hospital-acquired-and-ventilator-associated-bacterial-pneumonia. Accessed May 14, 2023.