History of Popular Medications for Type 2 Diabetes


Do you ever wonder how some of the treatments used to manage type 2 diabetes were created? We know that the ultimate goal is to keep your glucose levels within a healthy range and delay or prevent any other health issues. 

But as a person with type 2 diabetes, gaining a little extra knowledge on why the medications used to treat your chronic illness doesn’t hurt. In fact, you can use the info in this article to educate others—even your own doctor—on why these medications were created in the first place. It’s also helpful to understand just how far we’ve come when it comes to treating type 2 diabetes. 

As your read and consider trying new medications to treat your type 2 diabetes, remember that each medication may work better for you than others. Please consult your doctor about which one may be best for you. 

Let’s start with the most common one: metformin. 


You know metformin is the first medication doctors prefer to prescribe after your diagnosis. But metformin’s history is quite interesting. While there are diabetes medications that aren’t prescribed often nowadays, metformin is one that has truly stood the test of time. Here’s some interesting history behind this popular yet inexpensive treatment for type 2 diabetes. 

Metformin was derived from a European herbal plant called Goat’s Rue, which was shown to lower blood glucose in the early 20th century. While this plant was used to treat diabetes in the 1920s and 30s, its toxicity and the discovery of insulin led to it being discontinued as a real treatment. 

In 1957, Jean Sterne, a French physician was the first person to use metformin to treat diabetes. But even then, metformin hardly got any attention due to the risk of lactic acidosis. It wasn’t until the mid-90s that metformin’s benefits were being rediscovered after the UK Prospective Diabetes Study. It investigated if there were any benefits, specifically cardiovascular ones, of metformin when used for intensive glucose treatment. 

In 1998, it was approved under the name Glucophage, by the U.S. Food and Drug Administration (FDA), and became the first line of treatment for type 2 diabetes. Today, metformin remains the first line of treatment because, in addition to being effective at improving blood glucose levels and helping reduce A1C by 1-2 percent, there’s no risk of hypoglycemia, helps with weight loss and it’s inexpensive. 


Sulfonylureas (SFUs) are the second most common treatment for type 2 diabetes, but the longest-used. SFUs lower blood glucose by squeezing insulin out of the pancreas and helps improve insulin sensitivity. This class of drugs was discovered in the 1940s after researchers found that people being treated for typhoid were experiencing hypoglycemia. In the mid-50s, tolbutamide was introduced as the first sulfonylurea in Germany. Several other first-generation SFUs such as tolazamide, chlorpropamide and acetohexamide were discovered around the same time. In the mid-80s, second-generation SFUs that are still used today—glyburide and glipizide—was introduced in the U.S., followed by the third-generation glimepiride which was approved in 1995. 

Just like with metformin, the UKPDS study showed SFUs benefit people with diabetes by reducing the risk of microvascular complications and the ADVANCE (Action in Diabetes and Vascular Disease) study showed it actually improved that aspect of health, particularly diabetic nephropathy (diabetic kidney disease). 

Nearly 60 years later, SFUs are still useful in helping people with type 2 diabetes improve their blood glucose levels. They can help reduce A1C by 1-2 percent and are also ideal because they’re inexpensive. However, some precautions for using them include the risk of hypoglycemia and slight weight gain. Also, after years of use, their effectiveness may decline. 


Insulin—the most widely known medication used to treat diabetes—was discovered in 1921 by Frederick Banting and his assistant, Charles Best. Prior to its discovery, people with diabetes were put on very strict diets—near-starvation diets–with few carbs. Banting and Best derived insulin from a dog’s pancreas and used it to save the lives of animals and later, humans with diabetes. 

Years later, insulin from pigs and cattle was used and in 1978, human insulin was created by using E. Coli bacteria in its production. In the early-80s, Eli Lilly and Company started producing Humulin R/Regular and N/NPH, these products becoming the first commercially available biosynthetic human insulin.

Analog insulin was a game-changer after the first short-acting insulin analog, lispro, was approved by the FDA in 1996. The other short-acting insulin, aspart was approved in 2000. Long-acting insulin analogs glargine and detemir were approved in 2000 and 2005, respectively. Even though they’re more expensive than human insulin, analog insulins have proven to be more predictable and take effect quicker than human insulin, and are preferable to human insulin. Human insulin can clump when injected into the skin, which can slow absorption and make it unpredictable. 

Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs) 

GLP-1s are a relatively new medication for type 2 diabetes. They improve blood  glucose levels by suppressing the release of glucagon (the hormone that raises blood glucose), delaying gastric emptying and suppressing appetite. 

The first GLP-1, exenatide (Byetta), was approved in 2009 by the FDA. Exenatide was directed to be taken twice per day before morning and evening meals. Over the last decade, other GLP-1s have become available. Some GLP-1s can be taken once per week and others once per day. Also, GLP-1s were injectables until 2019 when the oral semaglutide, Rybelsus, became available as an oral medication to be taken at least an hour before meals. 

GLP-1s have fast-become a preferred treatment by people with diabetes and doctors alike. In addition to improving blood glucose levels, they aid in weight loss, have cardiovascular benefits and have a low risk of causing hypoglycemia. The main side effect of this medication is nausea, but that can be dependent on the dosage and how it’s titrated for use. 

SGLT-2 Inhibitors 

SGLT-2 inhibitors are another newer class of medications. The first one, canagliflozin (Invokana), was approved by the FDA in 2013. A year later, dapagliflozin (Farxiga) was approved for use. SGLT-2s prevent the reabsorption of glucose in the kidneys and excrete the excess glucose through urine. 

Discovered in the late 1800s by German physician Joseph von Mering, it was shown that ingesting high levels of SGLT-2s improved glycemic control in animals with diabetes and also humans, when given high doses. 

Today, there are several brands of SGLT-2s available. But also, beyond its blood glucose-lowering effects, several landmark trials have shown that SGLT-2s have renal (kidney) and cardiovascular benefits, particularly reducing the risk of heart failure. Side effects can include a higher risk for urinary tract infections since these medications push glucose through the urine. It can also be combined with other medications such as metformin and insulin and is ideal for people with type 2 diabetes who are experiencing kidney issues. 

Thiazolidinediones (TZDs)

In the early 80s, Takeda Pharmaceuticals, based in Japan, discovered TZDs while researching another drug compound for people with type 2 diabetes. After making analog versions of it and testing them on rodents, the first TZDs were created and were shown to improve blood glucose levels and lipids. In 1997, troglitazone was approved for use but later removed because it caused liver damage. Two years later, rosiglitazone and pioglitazone were approved for type 2 diabetes treatment. In 2010, rosiglitazone’s approval was met with caution because of the possibility of it causing myocardial ischemia—meaning your heart isn’t getting enough blood and oxygen. Pioglitazone also has warnings for a slight risk in the increase of bladder cancer and has a side effect of edema, but it is approved to be used alone or in combination with other diabetes medications. It also shouldn’t be used in patients with heart failure. 

DPP-4 Inhibitors 

DPP-4 inhibitors benefit people with type 2 diabetes by increasing the hormone incretin, which helps stimulate the decrease in blood glucose levels by suppressing the glucagon hormone. Studies on the effectiveness of these drugs on blood glucose levels began in the 90s and continued into the 2000s. They were also studied alongside GLP-1s due to the similarities they share in regards to the incretin hormone. The first DPP-4 inhibitor, sitagliptin, was approved by the FDA in 2006. 

These medications are used mainly as an add-on to metformin when metformin alone isn’t effective in managing type 2 diabetes. It can also be the first line of medication in people who have renal issues and for people who can’t tolerate metformin. 

What’s Next for Medications for T2D Medications? 

Research is ever-evolving in the search for the next breakthrough in medications for people with type 2 diabetes. Check out this article on what’s on the horizon, including an exciting medication that’s shown to be more effective than insulin and GLP-1s in terms of weight loss, reducing A1C and reducing the risks of cardiovascular and renal diseases. 

Educational content related to type 2 diabetes is made possible with support from Lilly Diabetes. Beyond Type 2 maintains full editorial control of all content published on our platforms.

WRITTEN BY T'ara Smith, MS, Nutrition Education, POSTED 04/07/22, UPDATED 10/11/22

T’ara was diagnosed with type 2 diabetes in July 2017 at the age of 25. Since her diagnosis, she focused her academic studies and career on diabetes awareness and living a full life with it. She’s excited to have joined the Beyond Type 1 team to continue her work. Two years later, T'ara discovered she'd been misdiagnosed with type 2 and actually has latent autoimmune diabetes in adults (LADA). Outside the office, T’ara enjoys going to the movies, visiting parks with her dog, listening to BTS and cooking awesome healthy meals. T’ara holds an MS in Nutrition Education from American University.