From the Guidelines
For patients with uncontrolled type 2 diabetes who cannot tolerate metformin, a sulfonylurea is the recommended initial alternative medication, as per the World Health Organization guidelines 1. This recommendation is based on a strong recommendation with moderate-quality evidence. The guidelines suggest that sulfonylureas should be given to patients with type 2 diabetes who do not achieve glycemic control with metformin alone or who have contraindications to metformin. However, more recent guidelines from the American College of Physicians 1 suggest that SGLT-2 inhibitors or GLP-1 agonists may be added to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control, with high-certainty evidence. Considering the most recent evidence, the best approach would be to add an SGLT-2 inhibitor or a GLP-1 agonist to lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control who cannot tolerate metformin. Some key points to consider when choosing an alternative medication include:
- The patient's cardiovascular risk profile
- Kidney function
- Weight concerns
- Cost considerations
- Patient preference regarding injection versus oral administration It's essential to weigh these factors and consider the individual patient's needs when selecting the best alternative medication. In terms of specific medications, SGLT-2 inhibitors like empagliflozin or dapagliflozin, and GLP-1 agonists like semaglutide, dulaglutide, or liraglutide, are potential options. Ultimately, the choice of medication should be based on the most recent and highest-quality evidence, as well as individual patient factors.
From the FDA Drug Label
The provided drug label does not directly address the question of the best medication for someone with uncontrolled type two diabetes who is unable to tolerate metformin. The FDA drug label does not answer the question.
From the Research
Alternatives to Metformin for Uncontrolled Type 2 Diabetes
When metformin is contraindicated or not tolerated, several alternative medications can be considered for the treatment of uncontrolled type 2 diabetes.
- The choice of medication depends on various factors, including overall efficacy in A1c reduction, adverse effect profile, cost, and patient preference 2.
- Sulfonylureas, such as glipizide or glimepiride, and dipeptidyl peptidase-4 (DPP-4) inhibitors, such as saxagliptin or linagliptin, are potential alternatives to metformin 3.
- A systematic review found that sulfonylureas were more effective in lowering HbA1c levels, but were associated with a higher risk of hypoglycemia compared to DPP-4 inhibitors 3.
- Another study found that sitagliptin, a DPP-4 inhibitor, was non-inferior to glimepiride, a sulfonylurea, in reducing HbA1c levels, and was associated with a lower risk of hypoglycemia and weight loss 4.
- Combination therapy with a DPP-4 inhibitor, sulfonylurea, and metformin may also be effective in improving HbA1c levels, although this may not be suitable for patients who are intolerant to metformin 5.
Considerations for Selecting an Alternative Medication
When selecting an alternative medication to metformin, several factors should be considered, including: