What is the preferred order of prescribing oral hyping (hypoglyceric) medications, specifically oral anti-diabetic (diabetes) medications, for the treatment of diabetes mellitus?

From the Guidelines

The preferred order for prescribing oral diabetes medications typically begins with metformin as first-line therapy for most patients with type 2 diabetes, as it is the optimal first-line drug unless there are prevalent contraindications 1. The choice of metformin is based on its ability to decrease hepatic glucose production and improve insulin sensitivity, with the added benefits of weight neutrality or modest weight loss and low hypoglycemia risk.

Key Considerations

• The usual starting dose of metformin is 500 mg once or twice daily, gradually increasing to 1000 mg twice daily as tolerated.
• If metformin alone is insufficient to achieve glycemic targets, second-line options should be considered based on patient-specific factors such as cardiovascular risk, renal function, hypoglycemia risk, cost considerations, and weight concerns 1.
• A person-centered shared decision-making approach should guide the choice of pharmacologic agents for adults with type 2 diabetes, considering the effects on cardiovascular and renal comorbidities; effectiveness; hypoglycemia risk; impact on weight, cost and access; risk for adverse reactions and tolerability; and individual preferences 1.

Second-Line Options

• Sodium-glucose cotransporter-2 (SGLT2) inhibitors like empagliflozin (10-25 mg daily) or glucagon-like peptide-1 (GLP-1) receptor agonists are recommended for patients with established cardiovascular disease or high cardiovascular risk.
• Sulfonylureas (like glipizide 5-20 mg daily) or dipeptidyl peptidase-4 (DPP-4) inhibitors (like sitagliptin 100 mg daily) are alternative second-line options.

Third-Line Therapy

• Third-line therapy typically involves adding another agent from a different class, while considering the patient's comorbidities and preferences.
• Thiazolidinediones (like pioglitazone 15-45 mg daily) may be considered later in the treatment algorithm due to concerns about fluid retention and fracture risk.

Treatment Approach

• Treatment should be individualized based on efficacy, side effect profile, cost, and patient preferences, with regular monitoring and adjustment as needed 1.
• Early combination therapy can be considered in adults with type 2 diabetes at treatment initiation to shorten time to attainment of individualized treatment goals 1.
• The glucose-lowering treatment plan should consider approaches that support weight management goals for adults with type 2 diabetes 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION There is no fixed dosage regimen for the management of diabetes mellitus with glyburide tablets or any other hypoglycemic agent Patients Receiving Other Oral Antidiabetic Therapy:Transfer of patients from other oral antidiabetic regimens to glyburide tablets should be done conservatively and the initial daily dose should be 2. 5 to 5 mg. When transferring patients from oral hypoglycemic agents other than chlorpropamide to glyburide tablets no transition period and no initial or priming dose are necessary When transferring patients from chlorpropamide, particular care should be exercised during the first two weeks because the prolonged retention of chlorpropamide in the body and subsequent overlapping drug effects may provoke hypoglycemia.

The preferred order of prescribing oral hypoglycemic medications is not explicitly stated in the provided drug labels. However, the labels provide guidance on transferring patients from other oral antidiabetic therapies to glyburide or saxagliptin.

• Transfer from other oral antidiabetic agents: The labels suggest that transfer from other oral antidiabetic agents to glyburide should be done conservatively, with an initial daily dose of 2.5 to 5 mg.
• No specific order: There is no specific order of prescribing oral hypoglycemic medications mentioned in the labels.
• Caution with chlorpropamide: Particular care should be exercised when transferring patients from chlorpropamide to glyburide due to the risk of hypoglycemia. 2

From the Research

Preferred Order of Presing Oral Hypoglycemic Medications

The preferred order of prescribing oral hypoglycemic medications, specifically oral anti-diabetic medications, for the treatment of diabetes mellitus is as follows:

• Metformin is the first-line pharmacological therapy for type 2 diabetes, as stated by 3 and 4.
• For second-line therapy, the American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) guidelines recommend SGLT2 inhibitors or GLP1 RAs for patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease 3.
• For patients without these conditions, the ADA/EASD lists five options of noninsulin second-line therapy without a suggested hierarchy of use, including DPP4 inhibitors, sulfonylureas, and thiazolidinediones 3.
• The American Association of Clinical Endocrinologists/American College of Endocrinology lists nine hierarchical options, with GLP1 RAs as the first recommended therapy, followed by SGLT2 inhibitors and DPP4 inhibitors, and sulfonylureas as the last option 3.
• The choice of second-line therapy should be based on a comprehensive assessment of the risks and benefits, taking into account patient-specific factors such as cardiovascular risks, risk of hypoglycemia, metabolic changes, and cost 4.

Comparison of Second-Line Therapies

A comparison of second-line therapies, including sulfonylureas and DPP4 inhibitors, suggests that:

• Sulfonylureas have a higher efficacy in lowering HbA1c, but may have a higher risk of hypoglycemic events 4.
• DPP4 inhibitors may be considered as a clinically stable choice for second-line therapy, especially in patients with a high risk of hypoglycemia 4.
• The STEPS approach (safety, tolerability, efficacy, price, and simplicity) can be used to evaluate pharmacotherapy options for type 2 diabetes mellitus 5.

Controversies and Debates

There are controversies and debates regarding the use of sulfonylureas as a first-line add-on to metformin therapy, with some arguing that they should no longer be considered a first-line option due to the availability of newer drugs with equal glucose-lowering efficacy and greater safety 6.

• The use of metformin as the first-line therapy for type 2 diabetes has been questioned, with some arguing that other anti-hyperglycemic medications may exhibit additional advantages in certain populations 7.
• However, metformin remains a widely used and effective treatment option, and its initiation should not be delayed, especially in patients with high-risk profiles 7.