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What Medications Can Be Used As a Substitute for Metformin

By Matt Knouff ; Updated July 27, 2017

Metformin is a prescription medication used for treatment of type 2 (non-insulin dependent) diabetes. Other medications may be considered if metformin does not adequately treat your type 2 diabetes.


Types of medications for treating type 2 diabetes include dipeptidyl-peptidase 4 inhibitors such as Onglyza and Januvia, glucagon-like peptide 1 agonists such as Byetta, meglitinides such as Prandin and Starlix, sulfonylureas such as Glucotrol, Amaryl and Glynase, thiazolidinediones such as Avandia and Actos and alpha-glucosidase inhibitors such as Precose and Glyset.


DPP-4 inhibitors, GLP-1 agonists, meglitinides and sulfonylureas increase insulin production, thiazolidinediones increases the effectiveness of insulin without increasing insulin production and alpha-glucosidase inhibitors blocks certain stomach enzymes that make the body more sensitive to insulin.


Byetta is available only as an injectable. The other types of medications are taken orally.

Side Effects

Sulfonylureas and thiazolidediones may cause weight gain. DPP-4 inhibitors increase risk of respiratory infections. Consult your pharmacist or physician for a more comprehensive list of side effects for each particular medication.

Lactic Acidosis

Metformin may cause lactic acidosis, which is a condition caused by excessive buildup of lactic acid in the body. Symptoms of lactic acidosis include weakness, drowsiness, decreased heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, lightheadedness and fainting. Other types of type 2 diabetes medications are not associated with development of lactic acidosis.

Diabetic Ketoacidosis

Metformin is contraindicated in cases of diabetic ketoacidosis, a condition caused by a shortage of insulin in the body. DDP-4 inhibitors, GLP-1 agonists, meglitinides and sulfonylureas should be considered in lieu of metformin in cases of diabetic ketoacidosis, because these medications increase production of insulin.

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