 Let's start with the most common medication on the market, Metformin. It's first line treatment after a diagnosis of type 2. Plenty of studies have shown its effects in decreasing blood glucose levels and potentiating the effects of insulin, but a full picture of its mechanisms of action still eludes us. Here are three things we know it does, it decreases output of glucose from the liver, it decreases absorption of glucose from the GIT, and it increases glucose uptake in skeletal muscle cells. Most of this is thought to occur via its action on AMPK, an enzyme that plays an important role in cellular energy management. Solvenolureas are next in line, these have a well defined mechanism of action. So this outline here is a pancreatic beta cell. This is an ion channel specific for potassium. If ATP hops on here, the channel is closed, and if solvenolurea hops on it'll have the same effect. Closing this channel leads to a build up of potassium inside the cell, and because there's now a higher proportion of cations in the cell, the charge will become less negative for overall, closer to the charge outside of the cell, and hence the cell will depolarise. Depolarisation causes these calcium channels to open up, allowing calcium to rush into the cell, and influx of calcium in a pancreatic beta cell causes secretion of insulin. As a quick summary, solvenolureas, the second line, type 2 diabetes, oral agent, increase the amount of insulin released by beta cells. After trying these both, if the patient's HPA1c still doesn't look much good, you can add a third oral therapy. The options are broader here. We'll start with the gliptins. To understand how these work, we need to know about glucagon like peptide, or GLP1. When certain food hits the GIT, GLP1 gets released from cells in the gut wall, then heads to the pancreas to stimulate the release of insulin. Which sounds great, but after it's released, GLP1 is quickly degraded by an enzyme called dipeptidal peptidase 4, or DPP4. The gliptins inhibit this enzyme, and thus increase the presence of GLP1. Next up in the recommendations are the glyphosins. These inhibit a transporter in the kidney called Sodium Glucose Co-Transporter 2, or SGLT2. This transporter is one of the key players responsible for getting glucose back into the blood after it's been filtered into the nephron tubules. If you block that transporter, you'll end up with less glucose in the blood, and more being peed out. You ripper. The way I like to remember it is this drug flows in, and glucose flows out in your urine. The next recommendation is an easy one to comprehend. They essentially act as analogs for GLP1, who we mentioned before. They are the tides, such as lyraglutide. They copy the action of glucagon like peptide, and that's why we give them names like lyraglutide. The algorithm I'm following only recommends the following two drugs, if the others are contraindicated, but I will chuck them in here for completeness. So we've got acarbose, a drug that inhibits an enzyme called alpha-glucosidase. Alpha-glucosidase usually breaks down long chains of carbohydrates to a size which can then be absorbed through the intestine wall and into the blood. The problem with this drug is that if you block this enzyme, you've got these long chain carbohydrates going straight through you, and this leads to the adverse drug effects of flatulence in 78% of people who take the drug. So you can understand why it's not that popular. And lastly, the glitterzones, which also go by the unpronounceable name of thiazolidinodions, or TZDs, I'm never going to say that again. These activate a nuclear receptor, which promotes transcription of genes relating to metabolism of carbohydrates, the utilization of energy. So they encourage cells to use glucose for their oxidative purposes, thereby reducing the amount in circulation. The glitterzones were shown to have an association with increased fluid retention and have thus fallen out of favor a few years ago. So as of 2017, that's it for oral diabetic medications. Remember, algorithms like this can be useful, but risk-providing prescribes is a formula to be relied on overpatient-specific care. Okay, thanks for watching, hit subscribe, and we'll see you next time.