medicine
“While primary care physicians may still adhere to the old idea that metformin is the ‘first choice,’ I think most endocrinologists have been using GLP-1 receptor agonists and SGLT2 inhibitors as best-in-class treatments for nearly a decade,” says Michael Uzman, M.D., a double-certified endocrinologist at A1Endocrinology in Las Vegas.
Dr. Menachem Jacobs, medical co-founder of Outlive Biology and resident physician at Yale New Haven Hospital in Connecticut, agrees. “Recently…I changed my strategy. My priority now is to protect my kidneys and heart immediately,” he says. “My go-to drugs for patients with kidney disease or heart failure are SGLT2 inhibitors or GLP-1 agonists. They really save the organ.”
Here we will introduce the main diabetes treatment drugs.
Biguanides
Metformin is the only drug in its class available in the United States and the only antidiabetic drug for prediabetes recommended by the American Diabetes Association (ADA) for some high-risk adults. It works by reducing the amount of sugar your liver makes and increasing your body’s use of insulin.
Side effects of metformin include nausea, diarrhea, and vomiting, but it is often effective when taken with food. People with decreased kidney function, heart failure, or alcohol dependence should not take metformin. Long-term use can cause vitamin B12 deficiency.
GLP-1 receptor agonist
These drugs mimic the natural hormone that tells your body to produce insulin when you eat. It also slows down digestion and reduces appetite, which helps in significant weight loss. Most are taken as injections, but some are available as tablets.
This class of drugs includes:
- Dulaglutide (Trulicity)
- Exenatide (Byetta)
- Liraglutide (Victoza)
- Lixisenatide (Adrixin)
- Semaglutide (Ozempic, Rybelsus)
Side effects of GLP-1 receptor agonists include nausea, vomiting, diarrhea, and rarely pancreatitis.
dual and triple agonists
These are newer, more powerful drugs that target multiple hormone receptors to lower blood sugar levels and promote weight loss. Dual agonists target both GLP-1 and GIP receptors. Triple agonists targeting GLP-1, GIP, and glucagon receptors are currently in clinical trials.
This class of drugs includes:
Possible side effects of tirzepatide include nausea, vomiting, diarrhea, and constipation.
SGLT2 inhibitor
Sodium-glucose cotransporter 2 (SGLT2) inhibitors work by preventing the kidneys from reabsorbing sugar, allowing it to be excreted in the urine. These drugs are highly recommended for people with heart failure or chronic kidney disease.
This class of drugs includes:
- Bexagliflozin (Brenzavi)
- Canagliflozin (Invokana)
- Dapagliflozin (Faciga)
- Empagliflozin (Jardiance)
- Ertugliflozin (Steglatro)
DPP-4 inhibitor
Dipeptidyl peptidase-4 (DPP-4) inhibitors help the body release more insulin when needed by blocking the enzyme that breaks down incretin hormones.
This class of drugs includes:
- Alogliptin (Nesina)
- Linagliptin (Trajenta)
- Saxagliptin
- Sitagliptin (Januvia)
Side effects of DPP-4 inhibitors include headaches, nausea, and joint pain. People who already have heart disease may also be at increased risk of pancreatitis and heart failure.
Sulfonylurea
These are some of the oldest diabetes medications. It works by stimulating the pancreas to release more insulin. Although effective and inexpensive, they carry a higher risk of hypoglycemia (low blood sugar) and weight gain.
This class of drugs includes:
- Glimepiride Glipizide
- Glyburide (DiaBeta)
Side effects of sulfonylureas include nausea, skin reactions (such as itching or rash), and diarrhea. These drugs are not recommended for people with kidney or liver disease.
Meglitinide
Meglitinides also work by promoting insulin release in the pancreas. They work fast. Possible side effects include hypoglycemia and weight gain.
Drugs in this class are repaglinide and nateglinide.
Thiazolidinedione
Thiazolidinediones (TZDs) improve insulin sensitivity, allowing the body to use insulin more effectively. It is now prescribed less frequently because of potential risks such as heart failure and bone fractures.
This class of drugs includes pioglitazone (Actos) and rosiglitazone.
D2 Argonist
Bromocriptine (Cycloset, Parlodel) is a supplemental oral medication that helps lower blood sugar levels in people with type 2 diabetes. Side effects include blurred vision, headache, and nausea. These side effects may disappear as your body gets used to the drug.
insulin
Insulin therapy may be required if oral medications or non-insulin injections alone cannot control blood sugar levels. Insulin works as a replacement for a hormone that your body doesn’t produce in enough.
“Most people with type 2 diabetes who require insulin start with a single injection of long-acting (basal) insulin once a day,” says endocrinologist Kathleen Dungan, M.D., of The Ohio State University Wexner Medical Center in Columbus.
