From the Guidelines
For patients who cannot tolerate metformin, a sulfonylurea such as glipizide or glyburide is often considered a good first-line alternative for type 2 diabetes, as recommended by the American Diabetes Association standards of medical care in diabetes 1.
Key Considerations
- Glipizide is typically started at 5 mg once daily before breakfast, with a maximum dose of 40 mg daily (usually divided if over 15 mg) 1.
- These medications work by stimulating insulin release from pancreatic beta cells, effectively lowering blood glucose levels.
- When prescribing sulfonylureas, be aware of potential hypoglycemia, especially in elderly patients or those with irregular eating patterns.
- Weight gain is another common side effect.
Alternative Options
- Other alternatives include DPP-4 inhibitors (like sitagliptin 100 mg daily), which have a lower risk of hypoglycemia and are weight-neutral, or SGLT-2 inhibitors (such as empagliflozin 10-25 mg daily), which offer cardiovascular benefits and promote weight loss.
- The choice should be individualized based on the patient's comorbidities, hypoglycemia risk, cost considerations, and specific contraindications.
Evidence-Based Recommendations
- The American Diabetes Association recommends a patient-centered approach, including assessment of efficacy, hypoglycemia risk, effect on weight, side effects, cost, and patient preferences 1.
- A table detailing characteristics of all available glucose-lowering agents in the United States that may guide individualized treatment choices is available in section 8 of the Standards 1.
From the FDA Drug Label
The efficacy of INVOKANA was compared to a dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin), both as add-on combination therapy with metformin HCl and sulfonylurea, and a sulfonylurea (glimepiride), both as add-on combination therapy with metformin HCl
The FDA drug label does not answer the question.
From the Research
Alternative First-Line Diabetic Medications
If a patient is intolerant of metformin, another good first-line diabetic medication to consider is:
- Sitagliptin, a dipeptidyl peptidase-4 inhibitor, which has been shown to be effective in improving glycemic control in patients with type 2 diabetes 2, 3, 4, 5, 6.
Efficacy and Safety of Sitagliptin
The efficacy and safety of sitagliptin have been demonstrated in several studies, including:
- A 52-week clinical trial that showed sitagliptin to be non-inferior to glipizide as an add-on agent in patients inadequately controlled on metformin alone 6.
- A 24-week trial that found sitagliptin to significantly improve glycemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycemic control with glimepiride or glimepiride plus metformin therapy 3.
- A 26-week study that demonstrated the addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated 5.
Benefits of Sitagliptin
The benefits of sitagliptin include: