I recently came across an interesting mnemonic: Ben Stiller Took Meg Griffin’s Dog Across Some Bridge. This puts in order, diabetes medication classes, from most effective, to least effective at decreasing A1c levels. The classes are as follows:
Biguanides
Sulfonylureas
Thiazolidinediones (TZDs)
Meglitinides
Glucagon-like peptide-1 receptor agonists (GLP1s)
Dipeptidyl peptidase-4 inhibitors (DPP4s)
Alpha Glucosidase inhibitors (AGIs)
Sodium/glucose cotransporter 2 inhibitors (SGLT2s)
Bile Acid Sequesters
First, we should define what A1c is. There are different types of hemoglobin, the protein that transports oxygen throughout our blood. The main kind in humans is called Hemoglobin A, which slowly bonds with glucose, forming hemoglobin A1c. I can’t find where the term “1c” comes from exactly. This process of adding a sugar molecule to hemoglobin happens spontaneously and slowly and creates a glycated hemoglobin. As your blood sugar increases, so does your hemoglobin A1c. The key here is that this is a process so your A1c levels are showing a weighted average over 120 days of your blood glucose levels. Neat. So managing that by decreasing that weighted average in Type 2 Diabetics in the following medication is important. Double neat. Let’s dive into the nine classes.
Biguanides are aptly first, as Metformin/Glucophage is a biguanide and is the third most prescribed medication in the US. It is available in two combination forms, with Sitagliptin: Janumet and with Empagliflozin: Synjardy. There are many benefits of biguanides. Their main MOA is the decrease of gluconeogenesis (the creation of glucose from non-glucose precursors) and the increase of peripheral utilization of glucose. It also improves your lipid profile (cholesterol) and reduces macrovascular risk. Common side effects of Metformin are GI-related, namely diarrhea. There is actually an extended-release type for this but it’s expensive.
Sulfonylureas are next. An example here is Glyburide/Glynase also known as Glibenclamide. This is the 200th most prescribed medication. Another is Glipizide/Glucotrol which is more popular (49th). Lastly we have Glimepiride/Amaryl (87th) which actually dropped 25 spots from 2019 to 2020. Sulfonylureas can cause weight gain and are metabolized in the liver and kidney. They can increase macrovascular risk yet Glipizide/Glucotrol is better for the elderly. THey work by increasing the secretion of insulin.
Next, the mouthful that are Thiazolidinediones or TZDs for short. These work by increasing the storage of fatty acids, so cells become more dependent on their oxidation of carbohydrates, specifically glucose. Examples here are the -glitazones. We have Pioglitazone/Actos (168th) as an example here. Like sulfonylureas, they can cause weight gain.
In fourth place we have the Meglitinides. There are two notable examples, Repaglinide/Prandin which you can take with renal failure and Nateglinide/Starlix which you can take with hepatic failure. Neither are on the top 300 list. Meglitinides are insulin secretagogues which means they increase insulin secretion.
In fifth place, we have the first of four of the long-named classes. Enter the glucagon-like peptide-1 receptor agonists. Whoa. We can call them GLP-1 for short. Remember that glucagon is secreted by alpha cells in the pancreas to increase blood sugar. They have a benefit over sulfonylureas and meglitinides as they have a lower risk of causing hypoglycemia. The GLP-1s all end in “-tide.” Examples are Dulaglutide/Trulicity (96), Semaglutide/Ozempic/Wegovy at 129, which should skyrocket as it has recently been used widely as a weight loss drug, and lastly Liraglutide/Victoza (146). These can cause nausea, vomiting, and diarrhea as well as gastroparesis. Wegovy is the higher-dose version of Ozempic and is marketed as an anti-obesity medication; it’s been in short supply recently in the US.
In sixth place we have the dipeptidyl peptidase-4 inhibitors or DPP-4 for short; they all end in -gliptin. Our first example here is Sitagliptin/Januvia (74). It can be combined with Metformin to create Janumet (154). The other two in the top 300 are Linagliptin/Tradjenta (293) and Alogliptin/Nesina (295). Side effects include pancreatitis, URI symptoms, and joint pain. Linagliptin/Tradjenta can be used in renal failure.
In seventh we have the Alpha-glucosidase inhibitors or AGI for short. These work by decreasing carbohydrate absorption in the GI tract. You want to avoid alcohol with these. An example here is Acarbose/Precose which is not on the top 300 list.
The penultimate eighth spot are the sodium/glucose cotransporter 2 inhibitors or SGLT2 for short. These all end in -flozin. Examples here are Empagliflozin/Jardiance (102), Dapagliflozin/Farxiga (217), and Canagliflozin/Invokana (294). You can combine Empagliflozin & Metformin to create Synjardy (238). These can cause weight loss alongside biguanides and GLP-1s. You want to avoid low carb diets and excessive alcohol here because you can go into DKA. SGLT2s along with TZDs can increase the risk of fractures. You also want strong kidney function to take these.
Our ninth and final spot are the elusive Bile Acid Sequesters. These are adjunctive only, meaning they are added onto something else. An example here is Colesevelam/Welchol. Don’t take these with gastroparesis. These can cause constipation and decreased vitamin ADEK absorption.
So there we have it! The nine classes of diabetes medications.