SGLT2 inhibitors

SGLT2 inhibitors are a newer class of diabetes medications that help lower blood sugar levels in people with type 2 diabetes mellitus. These drugs work through the kidneys instead of the pancreas, which makes them different from many older diabetes medicines. Over time, SGLT2 inhibitors have also shown important benefits beyond glucose-lowering, including support for heart disease, heart failure, and chronic kidney disease (CKD). Because of these added effects, they are now widely used in endocrinology, cardiology, and general diabetes care.

SGLT2 inhibitors are FDA-approved and commonly prescribed as part of a long-term treatment plan for people at high risk of cardiovascular disease or kidney problems. They may be used alone or in combination with other diabetes medications such as metformin, GLP-1 receptor agonists, or sulfonylureas. While generally well tolerated, they do come with specific side effects and warnings that patients should understand before starting therapy.

SGLT2 inhibitors, also known as sodium-glucose cotransporter-2 inhibitors, are prescription drugs used mainly to treat type 2 diabetes. They lower blood glucose by helping the body remove excess sugar through the urine. This class of drugs is often referred to as “gliflozins.”

Unlike insulin or medications that stimulate insulin release, SGLT2 inhibitors do not depend on how much insulin your body makes. This makes them useful at many stages of type 2 diabetes. They are not approved for type 1 diabetes, although some clinical trials have explored related medications such as sotagliflozin, which also affects SGLT 1.

In addition to improving glycemic control, SGLT2 inhibitors have been shown to reduce hospitalization for heart failure and slow the progression of chronic kidney disease in certain patients. Because of these benefits, healthcare providers may prescribe them even when blood sugar levels are already fairly controlled.

To understand how SGLT2 inhibitors work, it helps to know what the kidneys normally do. As blood passes through the kidneys, glucose is filtered out and then reabsorbed back into the bloodstream. This reabsorption happens through proteins called sodium-glucose cotransporters. One of the most important of these is sodium-glucose cotransporter-2, found in the kidneys.

SGLT2 inhibitors block this transporter. When it is blocked, glucose reabsorption is reduced, and excess sugar leaves the body in the urine as urinary glucose. This lowers blood glucose levels in a steady, insulin-independent way.

Because glucose pulls water with it, these drugs also have a mild diuretic effect. This can lead to lower blood pressure and slight weight loss, which may be helpful for people with obesity or cardiovascular disease. However, the fluid loss can also increase the risk of low blood pressure, especially in people already taking diuretics or who have reduced kidney function.

There are several FDA-approved SGLT2 inhibitors available in the U.S. and Canada. Common medications include:

• Jardiance (empagliflozin)
• Farxiga (dapagliflozin)
• Invokana (canagliflozin)
• Steglatro (ertugliflozin)
• Brenzavvy (bexagliflozin)

Some combination or related agents include Inpefa (sotagliflozin), which affects both SGLT2 and SGLT 1, although its use is more limited. These drugs are sometimes combined with other diabetes medicines to improve blood sugar control.

The main use of SGLT2 inhibitors is to lower blood sugar levels in adults with type 2 diabetes. They help improve long-term glycemic control and reduce A1C levels. Because they work through the kidneys, they can be effective even when insulin production declines over time.

Beyond diabetes, SGLT2 inhibitors are now commonly used to manage heart failure, including in people without diabetes. Studies have shown fewer hospitalizations and better outcomes in certain patients with heart disease. They are also used to slow the progression of chronic kidney disease, especially in people with diabetes and reduced estimated glomerular filtration rate (eGFR).

Healthcare providers may choose SGLT2 inhibitors for patients with multiple risk factors such as obesity, high blood pressure, cardiovascular disease, or CKD. They may be used alone or alongside other diabetes medicines like metformin or GLP-1 therapies.

Like all medications, SGLT2 inhibitors can cause side effects. The most common side effects are related to increased urinary glucose. These include urinary tract infections and genital infections, such as yeast infections. Good hygiene and staying hydrated can help lower this risk.

Other common side effects include increased urination, thirst, and mild dehydration. Because these drugs act as diuretics, some people may experience low blood pressure, dizziness, or lightheadedness, especially when standing up.

More serious but less common side effects include diabetic ketoacidosis, which can happen even when blood sugar levels are not extremely high. Symptoms may include nausea, vomiting, abdominal pain, fatigue, and rapid breathing. This condition requires immediate medical attention.

These are not all of the possible side effects of SGLT2 inhibitors. You should always seek medical advice from your healthcare provider for any questions or concerns about your medical condition or treatment. Read all patient information, medication guides, or drug information sheets that come with this medication. You can also report adverse effects to the Food and Drug Administration at www.fda.gov/medwatch or 1-800-FDA-1088.

SGLT2 inhibitors are generally considered safe and well-tolerated for many people. Large clinical trials and real-world use have shown benefits that often outweigh the risks when prescribed appropriately. However, safety depends on individual health factors, kidney function, and other medications being used.

Because they affect fluid balance and kidney function, careful monitoring is important. Regular blood tests may be needed to check kidney function, blood glucose levels, and ketone levels in some patients. A healthcare team will assess risks and benefits before starting therapy and during long-term use.

Warnings

Before starting SGLT2 inhibitors, it is crucial to discuss any existing health conditions with your healthcare provider. You should be sure that your healthcare provider is aware of all your medical conditions, including if you have:

• Chronic kidney disease or reduced eGFR
• A history of diabetic ketoacidosis
• Frequent urinary tract infections or genital infections
• Low blood pressure or dehydration
• Heart failure or cardiovascular disease
• Liver disease

People who are elderly, on diuretics, or who have multiple risk factors may need closer monitoring.

Contraindications

• SGLT2 inhibitors are not recommended for people with type 1 diabetes due to the increased risk of diabetic ketoacidosis. They are also generally avoided in patients with severely reduced kidney function, end-stage kidney disease, or those on dialysis. A healthcare professional will determine if kidney function is adequate before prescribing these medications.

Drug interactions

When SGLT2 inhibitors are taken with other prescription drugs, over-the-counter medications, vitamins, and supplements, they may change how they work or increase the frequency or severity of side effects. Make sure that you tell your healthcare professional about anything that you are taking to avoid any negative drug interactions, including:

• Diuretics, which may increase the risk of low blood pressure
• Insulin or sulfonylureas, which can raise the risk of hypoglycemia
• Other glucose-lowering diabetes medicines
• Blood pressure medications

Close monitoring may be needed when starting or adjusting doses.