From the Guidelines
If a patient is intolerant to metformin, consider alternative glucose-lowering medications such as SGLT-2 inhibitors or GLP-1 receptor agonists, which have been shown to have cardioprotective effects and can be used as first-line therapy in patients with established cardiovascular disease or high risk 1. When selecting an alternative medication, consider the patient's specific needs and comorbidities, including renal function, weight considerations, and hypoglycemia risk. Some key points to consider when choosing an alternative medication include:
- SGLT-2 inhibitors, such as empagliflozin or dapagliflozin, may decrease the risk of cardiovascular events and heart failure hospitalization 1.
- GLP-1 receptor agonists, such as semaglutide or dulaglutide, may decrease the risk of cardiovascular events and promote weight loss 1.
- DPP-4 inhibitors, sulfonylureas, and insulin therapy may be considered as alternative options, but should be used with caution and individualized based on patient preferences and comorbidities 1. It is essential to individualize treatment based on efficacy, side effect profile, cost, and patient preferences to ensure optimal glycemic control and adherence. In patients with chronic kidney disease, metformin may be used with caution, and the dose should be reduced or withdrawn based on the estimated glomerular filtration rate (eGFR) 1. Ultimately, the choice of alternative medication should prioritize the patient's morbidity, mortality, and quality of life outcomes.
From the FDA Drug Label
VICTOZA has been studied as monotherapy and in combination with one or two oral anti-diabetic medications or basal insulin.
The patient can proceed with liraglutide (VICTOZA) monotherapy if intolerant to metformin, as it has been studied as monotherapy in adults with type 2 diabetes mellitus.
- The dose of VICTOZA can be started at 0.6 mg/day and increased in weekly intervals by 0.6 mg to reach 1.2 mg or 1.8 mg.
- Treatment with VICTOZA 1.8 mg and 1.2 mg resulted in a statistically significant reduction in HbA1c compared to glimepiride 2.
From the Research
Alternatives to Metformin
If a patient is intolerant to metformin, there are several alternative pharmacological options available.
- The study 3 discusses various pharmacological options for persons with type 2 diabetes who cannot take metformin and do not accept/require insulin.
- Another study 4 suggests that efforts should be made to maintain metformin before considering a shift to another drug therapy, and discusses strategies to overcome metformin gastrointestinal intolerance, including the use of extended-release metformin and alternative pharmacological therapies.
Choice of Alternative Therapy
The choice of alternative therapy to metformin depends on various factors, including the patient's specific needs and medical history.
- A systematic review and meta-analysis 5 compared the treatment effects of different glucose-lowering drugs as initial monotherapy for type 2 diabetes patients with contraindications or intolerance to metformin, and found that GLP-1RAs showed an integrated beneficial effect on all outcomes.
- Another study 6 found that SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and major cardiovascular adverse events compared to other classes of glucose-lowering drugs.
Combination Therapy
Combination therapy with other glucose-lowering drugs may also be considered for patients who are intolerant to metformin.
- A study 7 found that the combination of GLP-1 RAs, DPP-4i, and SGLT-2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas.
- The same study 7 also found that GLP-1 RAs can significantly reduce body weight and basic insulin dosage, while DPP-4i and SGLT-2i have a lower risk of hypoglycemia.
Considerations for Treatment
When choosing an alternative therapy to metformin, several factors should be considered, including the patient's cardiovascular risk profile and the potential benefits and risks of different treatment options.