I decided to take a break from doing my antibiotic series of brush letter pharm to do a review of our glucose lowering agents instead. This short review will cover mechanism of action, side effects, weight effects and A1c lowering of our 6 big classes: Biguanide, DPP-4, GLP-1 agonists, Meglitinides, Sulfonylureas and TZDs (side note, it is very difficult to find consistent reporting of A1c lowering of these agents, I did my best to report generally what I've seen in most literature). And before you ask, yes, I left out insulin on purpose. I'll cover that sometime in the future. Enjoy!

Biguanides: Metformin
oral agent

• A1c lowering: 1-2%
• MOA: decrease hepatic glucose output, decrease glucose absorption and enhance insulin sensitivity. Work better on fasting blood glucose levels (FBG).
• Side effects: nausea, diarrhea, cramping, rare/life-threatening lactic acidosis esp. in patients with hepatic or renal impairment
• Effects on weight: neutral/loss

Sulfonylureas: Glipizide, Glimepiride, Glyburide
oral agent

• A1c lowering: 0.8-1%
• MOA: increase insulin secretion from pancreatic beta cells by regulating ATP-sensitive K+ channels. Have effects on both fasting and post-prandial glucose (PPG).
• Side effects: hypoglycemia, weight gain
• Effects on weight: gain

Meglitinides: Repaglinide, Nateglinide
oral agent

• A1c lowering: 0.7-1%
• MOA: Regulate ATP-sensitive K+ channels on pancreatic beta cells to help improve insulin secretion (same MOA as sulfonylureas, different binding site). Reduces PPG more than FBG.
• Side effects: hypoglycemia, weight gain
• Effects on weight: gain

SGLT-2 Inhibitors: Canagliflozin, Empagliflozin, Dapagliflozin
oral agent

• A1c lowering: 0.8-1%
• MOA: inhibit SGLT-2 in the proximal tubule of the kidney which prevents reabsorption of glucose and subsequently causes glucose to be excreted from the body through urination
• Side effects: hypotension, polyuria, yeast infections, UTIs
• Weight: loss

DPP-4 Inhibitors: Sitagliptin, Saxagliptin, Linagliptin, Alogliptin
oral agent

• A1c lowering: 0.5%
• MOA: Inhibits DPP-4, enzyme that breaks down incretin hormone GLP-1. Potentiating action of GLP-1 leads to increased satiety, slowing of gastric emptying (therefore decreased appetite), and increased insulin secretion through glucose-dependent matters. Reduce PPG more so than FBG.
• Side effects: nausea, otherwise generally well-tolerated
• Effects on weight: neutral

GLP-1 receptor agonists: Exenatide, Liraglutide, Lixisenatide, Dulaglutide
injectable agent

• A1c lowering: 0.8-1%
• MOA: Potentiate the action of incretin hormone GLP-1 which leads to increased satiety, slowing of gastric emptying (therefore decreased appetite), and increased insulin secretion through glucose-dependent matters. Reduces PPG more than FBG.
• Side effects: nausea, diarrhea, cramping
• Effects on weight: loss

TZDs: pioglitazone, rosiglitazone
oral agent

• A1c lowering:1-1.25%
• MOA: inhibits PPAR-y which encourages storage of fatty acids and utilization of glucose. Enhances insulin sensitivity. Works on both FBG and PPG levels.
• Side effects: fluid retention (can lead to acute decompensated HF), fractures
• Effects on weight: gain