What medication can be added to a maximum dose of Metformin (Metformin hydrochloride)?

From the Guidelines

When adding a medication to maximum-dose metformin, consider sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1 RA, or basal insulin, with the choice based on patient factors and drug-specific effects. The selection of the medication to be added should be guided by the patient's clinical characteristics, such as the presence of established ASCVD or indicators of high ASCVD risk, other comorbidities, and risk for specific adverse drug effects, as well as safety, tolerability, and cost 1. Some key considerations include:

• A1C target and risk of hypoglycemia
• Weight considerations, with GLP-1 agonists or SGLT-2 inhibitors being beneficial for weight loss
• Kidney function, with SGLT-2 inhibitors offering additional protection for patients with heart failure or kidney disease
• Cardiovascular or kidney disease history, which may influence the choice of medication The medications that can be added to metformin work through different mechanisms, including:
• Sulfonylureas, which stimulate insulin release
• DPP-4 inhibitors, which prevent incretin hormone breakdown
• GLP-1 agonists, which increase insulin secretion and reduce glucagon
• SGLT-2 inhibitors, which increase glucose excretion through urine
• Thiazolidinediones, which improve insulin sensitivity
• Basal insulin, which can be considered for patients with severe hyperglycemia or catabolic features 1. Ultimately, the choice of medication should be determined by a healthcare provider based on the individual patient's health profile.

From the Research

Medication Options to Add to Metformin

• Sodium-glucose cotransporter-2 (SGLT2) inhibitors: These medications have been shown to be effective in reducing the risk of all-cause mortality compared to sulfonylureas in patients with type 2 diabetes taking metformin 2.
• Dipeptidyl peptidase-4 (DPP-4) inhibitors: Adding DPP-4 inhibitors to metformin has been found to be effective in improving glycemic control, with a greater decrease in HbA1c levels compared to increasing the metformin dose alone 3.
• Sulfonylureas: While sulfonylureas are commonly used in the treatment of type 2 diabetes, they have been found to be associated with a higher risk of all-cause mortality compared to SGLT2 inhibitors in patients taking metformin 2.
• Glucagon-like peptide-1 (GLP-1) receptor agonists: These medications have been shown to have significant positive effects on glycemia, as well as added benefits in patients with obesity, renal disease, heart failure, and cardiovascular disease 4.

Considerations for Adding Medications to Metformin

• The choice of medication to add to metformin should be based on individual patient factors, such as the presence of cardiovascular disease, renal disease, or other comorbidities 2.
• The potential for gastrointestinal adverse effects with metformin should be considered when deciding whether to increase the metformin dose or add another medication 5.
• The effectiveness of increasing the metformin dose versus adding another medication should be evaluated on a case-by-case basis, taking into account the individual patient's response to treatment and potential side effects 5, 3.