What is the recommended approach for using Januvia (Sitagliptin), Actos (Pioglitazone), Glimepiride, and Jardiance (Empagliflozin) in a patient with type 2 diabetes?

From the Guidelines

The recommended approach for managing type 2 diabetes with Januvia (Sitagliptin), Actos (Pioglitazone), Glimepiride, and Jardiance (Empagliflozin) is to initiate metformin first, then add a second agent based on patient-specific factors, with Jardiance often preferred as a second-line agent due to its cardiovascular and renal benefits.

• Metformin should be started at a dose of 500mg once or twice daily, gradually increasing to 1000mg twice daily as tolerated.
• If glycemic targets are not achieved with metformin alone, a second agent should be added, with Jardiance (10-25mg daily) often preferred due to its cardiovascular and renal benefits, particularly in patients with established cardiovascular disease or kidney disease.
• Januvia (100mg daily, adjusted for renal function) may be added or substituted if SGLT2 inhibitors are contraindicated.
• Glimepiride (1-8mg daily) should be used cautiously due to hypoglycemia risk, particularly in elderly patients or those with irregular eating patterns.
• Actos (15-45mg daily) is generally considered a later option due to its side effect profile, including fluid retention, weight gain, and fracture risk.
• When combining these medications, monitor for specific adverse effects, such as hypoglycemia with glimepiride, urinary tract infections and volume depletion with Jardiance, heart failure exacerbation with Actos, and adjust doses based on renal function for Januvia and Jardiance, as recommended by the American Diabetes Association 1.
• Regular monitoring of HbA1c every 3-6 months helps guide therapy adjustments, and a person-centered shared decision-making approach should guide the choice of pharmacologic agents, considering factors such as cardiovascular and renal comorbidities, hypoglycemia risk, and individual preferences 1.

From the Research

Combination Therapy for Type 2 Diabetes

The use of Januvia (Sitagliptin), Actos (Pioglitazone), Glimepiride, and Jardiance (Empagliflozin) in combination for the treatment of type 2 diabetes can be considered based on the patient's individual characteristics and medical history.

• Sitagliptin and Pioglitazone: According to 2, Sitagliptin can be used in combination with a thiazolidinedione (such as Pioglitazone) when treatment with either drug alone provides inadequate glucose control.
• Glimepiride: While there is no direct evidence provided for the use of Glimepiride in combination with the other three medications, it is a sulphonylurea that can be used to treat type 2 diabetes.
• Empagliflozin: As stated in 3, Empagliflozin has been shown to reduce mortality in patients with type 2 diabetes and significant cardiovascular risk factors, although its hypoglycaemic effect is moderate.

Recommended Approach

When considering combination therapy, the following points should be taken into account:

• DPP-4 inhibitor plus SGLT-2 inhibitor: As discussed in 4 and 5, combining a DPP-4 inhibitor (such as Sitagliptin) and an SGLT-2 inhibitor (such as Empagliflozin) appears to be an attractive approach, with complementary glucose-lowering effects and no significant increase in hypoglycaemia risk.
• Patient characteristics: The choice between a gliptin and a gliflozin may be guided by individual patient characteristics, such as obesity, hypertension, and renal impairment, as mentioned in 6.
• Fixed-dose combinations: Fixed-dose combinations of a DPP-4 inhibitor and an SGLT-2 inhibitor, such as saxagliptin-dapagliflozin and linagliptin-empagliflozin, are available and may simplify anti-hyperglycaemic therapy and improve drug compliance, as noted in 4 and 5.