What is an alternative medication to glipizide (a sulfonylurea) for managing hyperglycemia?

From the Guidelines

Metformin is a highly recommended alternative medication to glipizide for managing hyperglycemia, due to its effectiveness, safety, and potential cardiovascular benefits, as supported by the most recent evidence 1. As a first-line agent for type 2 diabetes, metformin typically starts at 500 mg once or twice daily with meals, gradually increasing to a maximum of 2000-2500 mg daily divided into two doses to minimize gastrointestinal side effects. Unlike sulfonylureas like glipizide, metformin works by decreasing hepatic glucose production and improving insulin sensitivity rather than stimulating insulin release. This mechanism provides several advantages: metformin is weight-neutral or may promote modest weight loss, carries minimal risk of hypoglycemia, and offers potential cardiovascular benefits, as shown in a study published in Diabetes Care 1. Some key points to consider when prescribing metformin include:

• Monitoring for side effects such as diarrhea and abdominal discomfort, which typically improve over time with gradual dose titration and taking the medication with food.
• Ensuring the patient's estimated glomerular filtration rate (eGFR) is ≥30 mL/min/1.73 m², as metformin may be safely used in people with this level of kidney function 1.
• Periodic testing of vitamin B12 levels, as metformin use is associated with increased risk of vitamin B12 deficiency and worsening of symptoms of neuropathy 1. Other alternatives to glipizide include DPP-4 inhibitors (like sitagliptin), SGLT-2 inhibitors (such as empagliflozin), GLP-1 receptor agonists (like semaglutide), thiazolidinediones (such as pioglitazone), or insulin therapy, depending on the patient's specific needs, comorbidities, and glycemic targets. However, metformin is generally considered the first-line treatment for type 2 diabetes due to its favorable profile, as supported by the most recent evidence 1.

From the Research

Alternative Medications to Glipizide

Several alternative medications to glipizide, a sulfonylurea, are available for managing hyperglycemia in type 2 diabetes. These include:

• Sitagliptin, a dipeptidyl peptidase-4 inhibitor, which can be used alone or in combination with metformin or a thiazolidinedione 2
• Repaglinide, a meglitinide analogue, which stimulates insulin release and can be used as monotherapy or in combination with other antidiabetic agents 3, 4, 5
• Saxagliptin, another dipeptidyl peptidase-4 inhibitor, which can be used alone or in combination with metformin, sulfonylurea, or thiazolidinedione 6
• Nateglinide, a meglitinide analogue, which stimulates insulin release and can be used as monotherapy or in combination with other antidiabetic agents 3

Key Characteristics of Alternative Medications

Some key characteristics of these alternative medications include:

• Sitagliptin: increases insulin secretion, inhibits glucose production, and can be used in combination with metformin or a thiazolidinedione 2
• Repaglinide: stimulates insulin release, reduces postprandial glucose excursions, and can be used in flexible meal schedules 4, 5
• Saxagliptin: increases insulin secretion, reduces hepatic glucose production, and can be used in combination with metformin, sulfonylurea, or thiazolidinedione 6
• Nateglinide: stimulates insulin release, reduces postprandial glucose excursions, and can be used as monotherapy or in combination with other antidiabetic agents 3

Efficacy and Safety of Alternative Medications

The efficacy and safety of these alternative medications have been evaluated in several clinical trials:

• Sitagliptin: shown to be noninferior to glipizide as an add-on agent in patients inadequately controlled on metformin alone, with a similar incidence of hypoglycemia and body weight gain compared to placebo 2
• Repaglinide: shown to achieve similar glycaemic control to glibenclamide and better glycaemic control than glipizide, with a lower incidence of severe hypoglycaemia 4, 5
• Saxagliptin: shown to lower HbA1c levels by about 0.5% when used alone, and to be well tolerated with common side effects including upper respiratory tract infection, headache, and urinary tract infection 6
• Nateglinide: shown to stimulate insulin release and reduce postprandial glucose excursions, with a similar incidence of hypoglycemia compared to repaglinide 3