Progress in diabetes treatment used to take decades. The first effective treatment for diabetes, insulin, entered the market in the 1920s. It took 30 years for a new treatment, sulfonylureas, to be introduced in 1955. Another 40 years later, in 1995, metformin became available. Since then, the story has changed remarkably. From the late ’90s on, the increase in new diabetes medications has been exponential. Particularly in the last decade, we’ve seen several new diabetes treatments emerge. Specifically, there’s been an explosion of non-insulin therapies, including: GLP-1 receptor agonists DPP-4 inhibitors SGLT2 inhibitors GLP-1 Receptor Agonists When we eat food and it reaches the small intestine, the small intestine responds by releasing GLP-1 (glucagon-like peptide 1), a type of hormone called an incretin that tells our bodies we’re full. GLP-1 receptor agonists are non-insulin injectable medications that reproduce and enhance the effectiveness of GLP-1. This extra punch of GLP-1 lowers blood sugar, suppresses appetite, and causes weight loss. Currently, the Food and Drug Administration (FDA) has approved several GLP-1 receptor agonists for the treatment of type 2 diabetes: Exenatide (Byetta, Bydureon) Albiglutide (Tanzeum) Dulaglutide (Trulicity) Liraglutide (Victoza) Lixisenatide (Adlyxin) Side effects of GLP-1 receptor agonists include gastrointestinal symptoms like nausea, vomiting and diarrhea. These effects tend to diminish over time. There have been some reports of kidney damage or failure, and there may be an increased risk of acute pancreatitis, but these serious side effects are rare. DPP-4 Inhibitors DDP-4 (dipeptidyl peptidase-4) inhibitors are oral medications that trigger the pancreas to release insulin by stopping the deactivation of GLP-1. That raises GLP-1 levels. Similar to GLP-1 receptor agonists, this lowers blood sugar, suppresses your appetite, and can cause weight loss. The FDA has approved four DPP-4 inhibitors to date: Sitagliptin (Januvia) Saxagliptin (Onglyza) Linagliptin (Tradjenta) Alogliptin (Nesina) There are also several medications available that combine DPP-4 inhibitors and other diabetes drugs. Side effects of DPP-4 inhibitors include slight increased risk of an upper respiratory tract infection, such as a stuffy nose or a sore throat, and of a urinary tract infection, like pain or burning during urination. You may also experience joint pain. SGLT2 Inhibitors SGLT (sodium-glucose cotransporter) 2 inhibitors are also oral drugs that treat diabetes. They help with a process that sends extra sugar out of your body through your urine. This results in weight loss, lower blood pressure, and lower blood sugar. The FDA has approved several SGLT2 inhibitors to treat type 2 diabetes: Canagliflozin (Invokana) Dapagliflozin (Farxiga) Empagliflozin (Jardiance) There are a few medications out there that combine SGLT2 inhibitors with other diabetes drugs, too. Side effects include a complication of diabetes called ketoacidosis, which occurs from too many acids, called ketones, in the blood. These medications also increase the risk of serious urinary tract and yeast infections. Considering These Treatments Now that there are so many options, differentiating what medication to prescribe—and when—has become difficult. Of course, there’s insurance coverage to consider, too. When I choose a medication for a patient, I consider the risks and benefits. In the American Diabetes Association (ADA) guidelines, there’s a clear preference to stick with the tried and true treatments, like metformin, insulin, and sometimes sulfonylureas. Newer therapies don’t yet have a place in the guidelines because it’s hard for the ADA to adopt, encourage, and highly recommend treatments that have no long-term data on safety. There are some niches where these new treatments are useful. They can be effective treatments for patients who are personally resistant to trying insulin. These drugs can also cause weight loss, so they may benefit patients who need to lose weight to control their diabetes. But patients need to be relatively close to their hemoglobin A1c goals for these medicines to help them. GLP-1 receptor agonists reduce hemoglobin A1c by about 1%, and DPP-4 inhibitors and SGLT2 inhibitors reduce A1c levels by 0.6 to 0.8%. In contrast, metformin, the standard diabetes treatment, reduces A1c levels 1 to 1.5%. Another thing to keep in mind is that diet and exercise together can reduce hemoglobin A1c by well over 1.5%—with no cost and no side effects. Since these new treatments have recently come to the market, there’s a lot we’re still learning about them. As time passes, perhaps we’ll find more ways they can be used to benefit patients. For now, as a general physician, I prescribe diet, exercise, and the treatment standards of metformin, insulin, and sulfonylureas to my patients with diabetes.