From the Guidelines
After metformin failure in a diabetic patient, the most appropriate next medication choice is to add an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications, as recommended by the American College of Physicians 1. This recommendation is based on high-certainty evidence and prioritizes the reduction of morbidity, mortality, and improvement of quality of life. When selecting between these two options, several factors should be considered, including:
- Cardiovascular disease status: For patients with established cardiovascular disease, either an SGLT-2 inhibitor or a GLP-1 receptor agonist would be preferred due to their cardiovascular benefits 1.
- Weight loss concerns: GLP-1 agonists offer significant weight loss benefits and may be preferred for patients primarily concerned with weight loss.
- Cost considerations: While newer agents like SGLT-2 inhibitors and GLP-1 agonists are preferred, sulfonylureas or DPP-4 inhibitors may be considered if cost is a major concern, though they lack the cardiovascular benefits of newer agents.
- Comorbidities and side effect profile: The choice of medication should be individualized based on patient-specific factors, including comorbidities, side effect profile, and patient preferences 1. Key medications to consider include:
- SGLT-2 inhibitors like empagliflozin or dapagliflozin, which offer cardiovascular and renal protective effects, modest weight loss benefits, and low hypoglycemia risk.
- GLP-1 receptor agonists like semaglutide, which provide significant weight loss benefits and cardiovascular benefits, particularly in patients with established cardiovascular disease.
From the FDA Drug Label
In this 26-week trial, 1,091 adult patients with type 2 diabetes mellitus were randomized to VICTOZA 0.6 mg, VICTOZA 1.2 mg, VICTOZA 1. 8 mg, placebo, or glimepiride 4 mg (one-half of the maximal approved dose in the United States), all as add-on to metformin. Treatment with VICTOZA 1. 2 mg and 1.8 mg as add-on to metformin resulted in a significant mean HbA1c reduction relative to placebo add-on to metformin and resulted in a similar mean HbA1c reduction relative to glimepiride 4 mg add-on to metformin
The diabetic medication to start a patient on if they have failed metformin (biguanide) therapy is liraglutide (VICTOZA), as an add-on to metformin.
- The recommended starting dose is 0.6 mg/day, which can be increased in weekly intervals by 0.6 mg to reach 1.2 mg or 1.8 mg for patients randomized to these higher doses.
- Liraglutide 1.2 mg and 1.8 mg have been shown to result in a significant mean HbA1c reduction relative to placebo and similar to glimepiride 4 mg, both as add-on to metformin 2.
From the Research
Diabetic Medication Options After Metformin Failure
When a patient fails to achieve adequate glycemic control with metformin, several second-line medication options can be considered. The choice of medication depends on various factors, including the patient's clinical characteristics, comorbidities, and potential side effects.
Medication Options
- Sulfonylureas (SUs): SUs can still be effective in patients who have failed metformin therapy, as they can stimulate beta-cell function and improve glycemic control 3. However, they may have a higher risk of hypoglycemia and weight gain.
- Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: DPP-4 inhibitors are a viable option as a second-line therapy, with similar glycemic efficacy to SUs and a lower risk of hypoglycemia 4, 5, 6.
- Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: SGLT2 inhibitors have additional benefits, including weight loss, blood pressure reduction, and cardiovascular risk reduction, making them a favorable option for patients with these comorbidities 4, 5, 6.
- Thiazolidinediones (TZDs): TZDs can also be considered as a second-line therapy, although they may have a higher risk of side effects, such as weight gain and fluid retention 4, 6.
- Glucagon-Like Peptide 1 (GLP-1) Agonists: GLP-1 agonists are another option, although they may have a higher risk of gastrointestinal side effects and are typically more expensive than other options 6.
- Basal Insulin: Basal insulin can be considered for patients who require more intensive glucose control, although it may have a higher risk of hypoglycemia and weight gain 6.
Patient-Specific Factors
When choosing a second-line medication, patient-specific factors should be taken into account, such as: