A Review of the Action of Diabetes Drugs

Last month I promised in a post on the importance of lifestyle that I was working on a review of diabetes medications – well, here it is! This is a tricky undertaking, especially since many medications are actually combinations of more than one. I’ve decided to show you exactly where, in the process of carbohydrate/glucose metabolism, medications act.

Process of carbohydrate metabolism

To start I should detail carbohydrate metabolism as follows:

  1. Eat potato
  2. Potato passes from stomach into small intestine
  3. Enzymes break down carbohydrate molecules (starch in the potato) liberating glucose
  4. Glucose is absorbed into your bloodstream, raising blood glucose levels
  5. Pancreas beta cells respond by releasing insulin (in type 1 diabetes and advanced type 2 diabetes insulin production is depleted)
  6. Insulin guides the absorption of glucose into muscle and liver cells for storage, bringing blood glucose levels down to normal range (in type 2 diabetes, cells lose sensitivity to insulin, leaving excess glucose circulating in blood)
  7. Cells use stored glucose for energy and absorb more glucose from blood, lowering blood glucose levels (in type 1 and type 2 diabetes, excess glucose removed by kidneys into urine when blood glucose levels are near 200 mg/dl)
  8. Pancreas alpha cells release glucagon, stimulating liver to balance blood glucose by dumping stored glucose back into blood (in type 2 diabetes the liver can be stimulated to release glucose even when glucose blood levels are higher))

Diabetes medications

Now, here’s a very brief review of available diabetes medications pinned to the steps listed above.

*Amylin memetics (injectable Symlin) is involved in steps #2, #4 and #8, slowing stomach emptying, reducing glucose absorption, and suppressing glucagon. This medication has a risk for hypoglycemia (low blood glucose).

*Alpha-glucosidase inhibitors (Precose, Glycet) are involved in step #3 by slowing the breakdown of starches and some sugars, reducing the amount of glucose available and slowing the absorption of glucose into the bloodstream.

*DPP-4 inhibitors (Onglyza, Januvia, Tradjenta, Nesina) and GLP-1 analogs (injectable Tanzium, Trulicity, Byetta and Byduron, Victoza and Saxenda, Adlyxin) are involved in steps #5 and #7 by stimulating the release of insulin when blood glucose is high, and by suppressing the release of glucose from liver cells.

*Sulfonylureas (Diabenese, Glucotrol, Micronase, Glynase, Diabetea, Amaryl) and Meglitinides (Prandin, Starlix) are involved in step #5 stimulating the pancreatic beta cells to produce more insulin. Both Sulfonylureas and Meglitinides carry a risk for hypoglycemia.

*Biguanides (metformin, Foramet, Glucophage, etc.) and Thiazolidinediones (Avandia, ACTOS) are involved in steps #6 and #8 by improving cell sensitivity to insulin, and suppressing glucose release from the liver.

Sodium-glucose transporter 2 (SGLT2) inhibitors (Invokana, Farxiga, Jardiance) are involved in step #7 by promoting the discharge of excess glucose into urine at a lower blood glucose level than what naturally occurs at around 200 mg/dl.

Insulin, of course, is injected (or inhaled) primarily at step #5, although long acting insulin plays a regulating role not related to food. All forms of insulin carry a risk for hypoglycemia.

There are many other options generally combining the medications listed above. Additionally, I have not included drugs called bile acid sequestrants, which seem to improve blood glucose control combined with other diabetes meds. This list leaves a lot of information unaddressed, but I thought showing the various “targets” in carbohydrate/ glucose metabolism would be interesting.

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