Closer Look at Diabetes Medications: DPP-4 Inhibitors vs. SGLT2 Inhibitors

Type 2 diabetes is a chronic condition marked by high blood sugar levels due to the body's inefficient use of insulin. It's different from type 1 diabetes, which usually begins in childhood and involves insufficient insulin production. Type 2 diabetes often develops in adults and is linked to lifestyle factors like poor diet, limited physical activity, and obesity. This condition can cause serious health issues such as heart disease, kidney damage, and nerve problems. Managing type 2 diabetes involves lifestyle changes, medications, and regular blood sugar checks.

Among the medications used to treat type 2 diabetes, two key classes are DPP-4 inhibitors and SGLT2 inhibitors. Understanding how these drugs work is vital for both patients and healthcare providers.

• DPP-4 Inhibitors

  These drugs enhance the body's natural ability to lower blood sugar levels. They work by helping the body produce more insulin and reduce the production of glucose in the liver.

• SGLT2 Inhibitors

  These medications assist the kidneys in removing excess glucose through urine. They do this by preventing glucose from being reabsorbed back into the blood from the kidneys.

In the treatment plan for type 2 diabetes, these medications are often used alongside lifestyle adjustments and other medications. This combined approach is crucial for effectively managing blood sugar levels and minimizing the risk of diabetes-related complications.

DPP-4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) inhibitors are identifiable by their generic names, which typically end in “gliptin.” Some common examples include:

• Sitagliptin (brand name: Januvia, Zituvio)
• Saxagliptin (brand name: Onglyza)
• Linagliptin (brand name: Tradjenta)
• Alogliptin (brand name: Nesina)

Mechanism of action: Targetting the DPP-4 enzyme

DPP-4 inhibitors work by inhibiting the DPP-4 enzyme, which breaks down key hormones like GLP-1 and GIP. By preserving the levels of these hormones, these medications help in enhancing the body's natural ability to regulate blood sugar levels.

• Hormones affected by DPP-4
  • Glucagon-Like Peptide-1 (GLP-1): This hormone enhances insulin secretion from the pancreas in response to eating, thereby lowering blood sugar levels. GLP-1 also slows gastric emptying and promotes a feeling of fullness.
  • Gastric Inhibitory Polypeptide (GIP): GIP also stimulates insulin release in response to food intake, though its role is more complementary to GLP-1.
• Impact of DPP-4 inhibition on these hormones
  By inhibiting the DPP-4 enzyme, DPP-4 inhibitors prevent the rapid breakdown of GLP-1 and GIP. This leads to increased levels of these hormones in the body, which in turn results in enhanced insulin secretion and better blood sugar control. The prolonged action of GLP-1 and GIP also helps in reducing appetite and slowing the absorption of nutrients from the gut, contributing to better overall glucose management.

Effectiveness of DPP-4 inhibitors

DPP-4 inhibitors are often chosen for patients who need additional help in managing their diabetes beyond what diet, exercise, and other medications provide.

Impact on weight: Unlike some diabetes medications that may cause weight gain, DPP-4 inhibitors are generally weight-neutral. This means they do not typically lead to weight gain or loss, which can be a significant advantage for many patients.

Comparison with GLP-1 agonists: While effective, DPP-4 inhibitors are sometimes considered less potent than GLP-1 agonists, another class of diabetes medication. GLP-1 agonists tend to have a more pronounced effect on lowering blood sugar and promoting weight loss. However, they may also have more side effects.

Other considerations: DPP-4 inhibitors are known for having fewer side effects compared to some other diabetes medications, making them a suitable option for many patients. However, they can be more expensive than other treatment options, which might be a consideration in treatment planning.

It's important to remember that the effectiveness of DPP-4 inhibitors, like all medications, can vary from person to person. Healthcare providers assess their suitability and effectiveness on an individual basis, taking into account each patient's unique health profile and diabetes management needs.

Side effects

• Cold symptoms
• Urinary tract infection or UTI
• Inflammation of your nose and throat
• Headaches
• Upset stomach, nausea
• Joint pain
• Hypoglycemia

SGLT2 Inhibitors

Sodium-glucose cotransporter-2 (SGLT2) inhibitors typically end in “gliflozin,” are a class of medications frequently used to lower high blood sugar levels in people with type 2 diabetes. These drugs are often prescribed alongside dietary changes and exercise.

• Canagliflozin (brand name: Invokana)
• Bexagliflozin (brand name: Brenzavvy)
• Dapagliflozin (brand name: Farxiga)
• Empagliflozin (brand name: Jardiance)
• Ertugliflozin (brand name: Steglatro)

Beyond diabetes—heart and kidney health: In addition to their role in diabetes management, certain SGLT2 inhibitors have gained FDA approval for use in chronic kidney disease (CKD) and heart failure. These approvals are based on evidence showing that SGLT2 inhibitors can lower the risk of heart attack, stroke, or worsening heart failure, even in individuals without diabetes. Furthermore, some of these medications have been recognized for their ability to slow the progression of kidney disease.

Mechanism of action: Targetting the SGLT2 protein

This drug class works by targeting a protein in your kidney called SGLT2, which plays a key role in reabsorbing glucose from urine into your bloodstream. By inhibiting SGLT2, these medications prevent the reabsorption of glucose, leading to increased excretion of glucose in your urine.

Lowering blood sugar levels by inhibiting glucose reabsorption: SGLT2 inhibitors block the action of the SGLT2 protein. This inhibition leads to excess glucose being excreted in urine instead of being reabsorbed.

Insulin independence: A key advantage of SGLT2 inhibitors is their ability to lower blood sugar levels independently of insulin. This is an important aspect, as many individuals with type 2 diabetes have insulin resistance, where their body doesn't use insulin effectively.

Effectiveness of SGLT2 inhibitors

Clinical studies have consistently shown that SGLT2 inhibitors can effectively lower hemoglobin A1c levels, a key indicator of blood sugar control. They also contribute to weight loss and can help in reducing blood pressure, making them a multi-faceted option for diabetes management.

Benefits beyong diabetes control: In addition to their primary role in managing blood sugar levels, SGLT-2 inhibitors have demonstrated significant benefits in slowing the progression of kidney disease. They are particularly effective in reducing the incidence of heart failure and the risk of kidney failure and mortality in individuals with both chronic kidney disease (CKD) and type 2 diabetes.

Kidney protection in non-diabetic CKD patients: The protective effects of these inhibitors extend to kidney health in patients with CKD who do not have diabetes, underlining their broad therapeutic potential.

Impact on heart health: There's growing evidence that certain SGLT-2 inhibitors can also benefit heart health. This is particularly true for individuals with a history of heart disease, where these medications have been linked to a lower risk of heart failure and a reduction in hospitalizations due to heart-related complications.

Side effects

• Urinary tract infection or UTI
• Increased urination
• Genital yeast infection
• Low glucose levels in your blood, or hypoglycemia
• Dehydration
• Low blood pressure
• Weight loss
• Increased blood ketone levels, also known as ketoacidosis

Things to consider when choosing between the two

Choosing between DPP-4 inhibitors and SGLT2 inhibitors for the treatment of type 2 diabetes depends on various factors, including the individual patient's health profile, specific treatment goals, and potential side effects. Here's a general guide on how to choose between the two:

Patient's Health Profile

• Kidney Function: SGLT2 inhibitors are often preferred in patients with certain kidney conditions due to their renal protective effects.
• Cardiovascular Health: SGLT2 inhibitors have shown benefits in reducing the risk of heart failure and cardiovascular events, making them a preferred choice for patients with existing heart conditions.
• Risk of Hypoglycemia: Both DPP-4 inhibitors and SGLT2 inhibitors have a low risk of hypoglycemia, but this might be a more significant concern in combination with other medications like sulfonylureas or insulin.

Treatment Goals

• Blood Sugar Control: Both classes are effective in lowering blood sugar, but SGLT2 inhibitors might offer greater reduction in A1c levels.
• Additional Health Benefits: If there's a need for additional health benefits like cardiovascular protection or renal protection, SGLT2 inhibitors might be preferred.

Potential Side Effects

• DPP-4 Inhibitors: Generally well-tolerated; potential side effects include upper respiratory tract infections, headache, and joint pain.
• SGLT2 Inhibitors: Risks include urinary tract infections, fungal infections, and a small increased risk of diabetic ketoacidosis.

Cost and Insurance Coverage

• SGLT2 inhibitors are often more expensive than DPP-4 inhibitors, and insurance coverage might influence the choice.

Brenzavvy an affordable SGLT2 inhibitor for type 2 diabetes&mash;available exclusively through Marley Drug for $59.95

Speak with your doctor

It’s recommended to talk to your doctor about whether to take DPP-4 inhibitors or SGLT2 inhibitors for type 2 diabetes to ensure a personalized therapy plan. As the choice between these drug classes depends on various factors, including your overall health, preferences, potential side effects, and specific comorbidities.

Speaking with your healthcare provider allows for a thorough assessment of these considerations, ensuring that the appropriate medication aligns with your health and goals for managing your condition.