There are many types of medication for type 2 diabetes. For a long time, a drug called metformin was the first choice for almost everyone. Although metformin is still often the first medicine physicians prescribe, many doctors are shifting to other medicines as first-line options.
“While primary care physicians may still follow the old idea that metformin is ‘first line,’ I think most endocrinologists have been using GLP-1 receptor agonists and SGLT2 inhibitors as best-in-class therapy for nearly a decade,” says Michael Uzmann, MD, a dual board-certified endocrinologist and internist at A1Endocrinology in Las Vegas.
Menachem Jacobs, MD, the medical cofounder at Outlive Biologyand a resident physician at Yale New Haven Hospital in Connecticut, agrees. “Recently … I shifted my strategy. I am now making it my top priority to safeguard the kidneys and heart right away,” he says. “My go-to medications for patients with renal disease or heart failure are SGLT2 inhibitors or GLP-1 agonists. Organs are really saved by them.”
Here are the main classes of diabetes medications.
Biguanides
Metformin is the only drug in this class available in the United States, and the only antidiabetic medication for prediabetes recommended for some high risk adults by the American Diabetes Association (ADA). It works by lowering the amount of sugar your liver makes and helping your body use insulin better.
Possible side effects of metformin include nausea, diarrhea, and vomiting, though taking it with food often helps. People with decreased kidney function, heart failure, or alcohol dependence should not take metformin. Long-term use may lead to vitamin B12 deficiency.
GLP-1 Receptor Agonists
These drugs mimic a natural hormone that tells your body to make insulin when you eat. They also slow down digestion and reduce appetite, which can help with significant weight loss. Most are taken as injections, though one is available as a pill.
Medications in this class include:
dulaglutide (Trulicity)
exenatide (Byetta)
liraglutide (Victoza)
lixisenatide (Adlyxin)
semaglutide (Ozempic, Rybelsus)
Possible side effects of GLP-1 receptor agonists include nausea, vomiting, diarrhea, and, rarely, pancreatitis.
Dual and Triple Agonists
These are newer, powerful medications that target multiple hormone receptors to lower blood sugar and drive weight loss. Dual agonists target both GLP-1 and GIP receptors. Triple agonists that target GLP-1, GIP, and glucagon receptors are currently in clinical trials.
Medications in this class include:
Possible side effects of tirzepatide include nausea, vomiting, diarrhea, and constipation.
SGLT2 Inhibitors
Sodium-glucose cotransporter-2 (SGLT2) inhibitors work by preventing the kidneys from reabsorbing sugar, allowing it to be excreted in urine. These drugs are strongly recommended for people with heart failure or chronic kidney disease.
Medications in this class include:
bexagliflozin (Brenzavvy)
canagliflozin (Invokana)
dapagliflozin (Farxiga)
empagliflozin (Jardiance)
ertugliflozin (Steglatro)
Possible side effects of SGLT2 inhibitors include urinary frequency, dizziness, vaginal yeast infections, urinary tract infections, and dehydration. In rare cases, these medications can cause serious complications like low blood pressure or diabetic ketoacidosis.
DPP-4 Inhibitors
Dipeptidyl peptidase-4 (DPP-4) inhibitors help the body release more insulin when needed by blocking the enzyme that breaks down incretin hormones.
Medications in this class include:
alogliptin (Nesina)
linagliptin (Tradjenta)
saxagliptin
sitagliptin (Januvia)
Possible side effects of DPP-4 inhibitors include headaches nausea, and joint pain. People with an existing heart condition may also be at increased risk for pancreatitis or heart failure.
Sulfonylureas
These are some of the oldest diabetes medications. They work by stimulating the pancreas to release more insulin. While effective and inexpensive, they carry a higher risk of hypoglycemia (low blood sugar) and weight gain.
Medications in this class include:
glimepiride glipizide
glyburide (DiaBeta)
Possible side effects of sulfonylureas include nausea, skin reactions (such as itching or rash), and diarrhea. These medications are not recommended for people with kidney or liver disease.
Meglitinides
Meglitinides also work by triggering the pancreas to release more insulin. They work quickly. Possible side effects include hypoglycemia and weight gain.
Medications in this class are: repaglinide and nateglinide.
Thiazolidinediones
Thiazolidinediones (TZDs) help improve insulin sensitivity, allowing your body to use insulin more effectively. They’re prescribed less frequently today due to potential risks like heart failure and bone fractures.
Medications in this class include: pioglitazone (Actos) and rosiglitazone.
D2 Argonist
Bromocriptine (Cycloset, Parlodel) is a supplemental oral medication that can help lower blood sugar levels in patients with type 2 diabetes. Side effects include blurred vision, headache, and nausea. These side effects may go away as your body adjusts to the medicine.
Insulin
If oral medications and non-insulin injectables aren’t enough to manage your blood sugar levels, you may need insulin therapy. Insulin acts as a replacement for the hormone your body isn’t producing enough of.
“Most patients with type 2 diabetes who require insulin start with a single injection of long-acting (basal) insulin given once daily,” says Kathleen Dungan, MD, an endocrinologist at the Ohio State University Wexner Medical Center in Columbus.