What are SGLT2 Inhibitors?

Have you heard of medications like Jardiance, Farxiga, or Brenzavvy? These drugs belong to a class called SGLT2 inhibitors, which have gained significant popularity in recent years for managing type 2 diabetes.

SGLT2 inhibitors, or sodium-glucose co-transporter 2 inhibitors, are prescription medications that primarily help control blood sugar levels. They work by preventing your kidneys from reabsorbing sugar, leading to increased glucose excretion in urine. This mechanism effectively lowers blood sugar levels.

While initially developed for diabetes management, ongoing research has revealed that these drugs offer even more. Beyond blood sugar control, certain SGLT2 inhibitors have been approved to slow kidney damage in chronic kidney disease (CKD) and reduce the risk of heart complications like heart attacks, strokes, and heart failure.

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Indications: Why are SGLT2 Inhibitors Prescribed?

In recent years, SGLT2 inhibitors have gained significant popularity due to their multifaceted benefits. Beyond diabetes management, their positive impact on heart health and kidney function has made them increasingly favored by healthcare professionals and patients alike.

• Type 2 Diabetes Mellitus (T2DM): SGLT2 inhibitors are primarily prescribed for managing type 2 diabetes mellitus. They can be used as monotherapy or in combination with other antidiabetic agents to help control blood sugar levels.
• Heart Failure: Certain SGLT2 inhibitors have received FDA approval for reducing the risk of cardiovascular death and hospitalization due to heart failure. These medications have proven to be beneficial for patients with heart failure, even if they do not have diabetes.
• Chronic Kidney Disease (CKD): SGLT2 inhibitors are approved for treating chronic kidney disease in adults, whether they have type 2 diabetes or not. These drugs help reduce the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure.

Benefits of SGLT2 Inhibitors

• Glycemic control: SGLT2 inhibitors work by blocking the reabsorption of sugar by your kidneys, leading to lower blood sugar levels. Clinical studies have shown that these medications can reduce A1C levels by around 0.5% to 1.0% on average.
• Weight management: Some patients experience modest weight loss, but it is not guaranteed. It's important to consult your doctor for weight management strategies that include a healthy diet and exercise plan, as SGLT2 inhibitors are not FDA-approved for weight loss.
• Blood pressure reduction: SGLT2 inhibitors can help reduce blood pressure, which is particularly beneficial for patients with hypertension or those at risk of cardiovascular complications.
• Cardiovascular and renal protection: Studies have shown that SGLT2 inhibitors may offer cardiovascular and renal benefits.

Individual responses to SGLT2 inhibitors may vary depending on factors such as baseline A1C levels, adherence to treatment, and lifestyle choices. SGLT2 inhibitors are prescription medications and should only be taken under the supervision of a healthcare professional.

Contraindications: Who Cannot Use SGLT2 Inhibitors?

SGLT2 inhibitors are generally safe for most people, but they may not be suitable for everyone. Certain conditions and circumstances can make these medications inappropriate.

You should avoid SGLT2 inhibitors if you:

• Have type 1 diabetes.
• Have a severe allergy to SGLT2 inhibitors.
• Have severe kidney impairment, end-stage renal disease, or are undergoing dialysis.
• Have a history of diabetic ketoacidosis (DKA).
• Are pregnant or planning to become pregnant.
• Are breastfeeding.

It's essential to discuss your medical history with your healthcare provider to determine if SGLT2 inhibitors are right for you. They can also recommend alternative treatment options if necessary.

Popular SGLT2 Inhibitors

Brenzavvy (Bexagliflozin)

• Use: Used for Type 2 diabetes
• Dose: 20 mg. Take orally once a day, preferably in the morning, with or without food.
• Afficacy: Clinical trials showed that approximately one-third of patients achieved an A1C level below 7% after six months of treatment, whether taken alone or with metformin.

Invokana (Canagliflozin)

• Use: For managing type 2 diabetes, reducing cardiovascular risk, and protecting kidney function in certain patients.
• Dose: 100 mg or 300 mg tablet taken once daily, preferably on an empty stomach.
• Afficacy: Reduces A1C levels by approximately 0.8% to 1% over 6.5 months, alongside diet and exercise.

Farxiga (Dapagliflozin)

• Use: For managing type 2 diabetes, reducing heart failure risk, and protecting kidney function.
• Dose: 5 mg or 10 mg tablet taken once daily, with or without food.
• Afficacy: Clinical trials have shown significant reductions in A1C levels, with a decrease of approximately 0.7% to 0.8% over 24 weeks.

Jardiance (Empagliflozin)

• Use: For managing type 2 diabetes, reducing heart failure risk, and protecting kidney function.
• Dose: 10 mg or 25 mg tablet taken once daily, with or without food.
• Afficacy: Clinical studies showed significant reductions in A1C levels, with a higher percentage of patients achieving the target A1C level compared to those on a placebo.

Steglatro (Ertugliflozin)

• Use: Used for type 2 diabetes.
• Dose: Available in 5 mg and 15 mg tablets, taken once daily, in the morning, with or without food.
• Afficacy: Clinical studies showed significant reductions in A1C levels, ranging from 0.7% to 1.1% over 26 weeks.

Inpefa (Sotagliflozin)

Unlike other SGLT2 inhibitors, this medication is part of a drug class of medications known as sodium-glucose co-transporter 1 and 2 inhibitors, commonly abbreviated as SGLT1/SGLT2 inhibitors.

By inhibiting SGLT-1 in the intestines, it reduces the absorption of glucose from your diet, and by inhibiting SGLT-2 in your kidneys, it increases the excretion of glucose in your urine. Its impact on glucose regulation may contribute to cardiovascular benefits, as suggested by clinical trials demonstrating a significant reduction in the risk of death and hospitalizations related to heart failure.

Inpefa's is not approved for lowering blood glucose levels in those with diabetes. However, it is possible to experience decreases in blood glucose as a side effect while using this medication.

• Use: For reducing heart failure risk, and protecting kidney function
• Dose: Available in 200 mg and 400 mg tablets, taken once daily, about 1 hour before breakfast or the first meal of the day.
• Afficacy: Clinical trials demonstrated significant reductions in the risk of death and hospitalizations related to heart failure.

Combination Medications

SGLT2 Inhibitor and Metformin

Combination pills that contain both an SGLT2 inhibitor and metformin are commonly prescribed for the management of type 2 diabetes. These medications work together to effectively control blood sugar levels by targeting different aspects of glucose metabolism.

By combining these two medications, you get a dual action against high blood sugar. The SGLT2 inhibitor reduces the amount of glucose that gets reabsorbed, and metformin decreases the amount of glucose produced by the liver. This combined effect often leads to better blood sugar control than using either medication alone.

• SGLT2 Inhibitors: These medications work by preventing the kidneys from reabsorbing glucose back into the body. Instead, the excess glucose is excreted in the urine, leading to lower blood sugar levels.
• Metformin: This drug primarily reduces the amount of glucose produced by the liver. It also improves the body's sensitivity to insulin, allowing the body to use insulin more effectively.

Examples include:

• Invokamet: canagliflozin (Invokana) and metformin
• Xigduo XR: dapagliflozin (Farxiga) and metformin
• Synjardy: empagliflozin (Jardiance) and metformin
• Segluromet: ertugliflozin (Steglatro) and metformin

SGLT2 Inhibitor and DPP-4 Inhibitors

Combination pills that include SGLT2 inhibitors and DPP-4 inhibitors provide a dual mechanism to enhance glycemic control in patients with Type 2 diabetes.

Combination drugs of SGLT2 inhibitors and metformin offer a multifaceted approach to managing Type 2 diabetes. By addressing both glucose production and excretion, these medications provide enhanced glycemic control, weight management benefits, cardiovascular and renal protection, and improved patient adherence. This combination therapy is a valuable option for patients seeking effective and convenient diabetes management.

• SGLT2 Inhibitors: SGLT2 inhibitors promote the excretion of excess glucose through urine, thereby lowering blood sugar levels.
• DPP-4 Inhibitors: These medications prolong the action of incretin hormones, leading to increased insulin production and decreased glucagon levels, which collectively help lower blood sugar levels.

Combining SGLT2 inhibitors and DPP-4 inhibitors in a single pill leverages the complementary mechanisms of both drug classes, offering several benefits:

• Enhanced Glycemic Control: The dual action helps to lower blood glucose levels more effectively than either drug alone, providing better overall glycemic control.
• Reduced Risk of Hypoglycemia:The mechanism of DPP-4 inhibitors is glucose-dependent, meaning they enhance insulin release only when blood glucose levels are high, reducing the risk of hypoglycemia.
• Weight Management: SGLT2 inhibitors often promote modest weight loss, which can be beneficial for patients managing Type 2 diabetes.
• Cardiovascular and Renal Benefits:SGLT2 inhibitors have been shown to provide cardiovascular and renal protection, which adds an extra layer of benefit for patients at risk of heart and kidney complications.

Examples include:

• Glyxambi: empagliflozin (Jardiance) and linagliptin (Trajdenta)
• Steglujan: ertugliflozin (Steglatro) and sitagliptin (Januvia, Zituvio)
• Synjardy: empagliflozin (Jardiance) and metformin
• Qtern: dapagliflozin (Farxiga) and saxagliptin (Onglyza)

Combination pills of SGLT2 inhibitors and DPP-4 inhibitors provide a robust approach to managing Type 2 diabetes by addressing blood sugar levels through multiple mechanisms. They offer enhanced glycemic control, reduced hypoglycemia risk, weight management benefits, and cardiovascular and renal protection, making them a valuable option for many patients.

Site Effects of SGLT2 Inhibitors

While SGLT2 inhibitors are generally well-tolerated, like all medications, they can cause side effects.

Common Side Effects

• Increased urination: This is a common side effect due to how SGLT2 inhibitors work.
• Yeast infections: Women may be more susceptible to yeast infections.
• Urinary tract infections: The increased urination can sometimes lead to urinary tract infections.
• Dehydration: Due to increased urination, it's important to stay hydrated.
• Increased thirst: This is often related to increased urination.

Serious Side Effects

While rare, some serious side effects can occur. It's essential to contact your healthcare provider immediately if you experience any of the following:

• Diabetic ketoacidosis: This is a serious condition characterized by high levels of ketones in the blood. Symptoms include nausea, vomiting, abdominal pain, shortness of breath, and fruity-smelling breath.
• Hypoglycemia: Although less common with SGLT2 inhibitors compared to other diabetes medications, it can still occur, especially when combined with insulin or other blood sugar-lowering drugs. Symptoms include shaking, sweating, dizziness, and confusion.
• Severe allergic reactions: These are rare but can be life-threatening. Symptoms include difficulty breathing, swelling of the face, lips, tongue, or throat, and rash.
• Bone fractures: Some studies have suggested a possible increased risk of bone fractures, particularly in women.