See Diabetes mellitus for treatment and disease info Also see Insulin production and effects
Biguanides (metformin)
BIguanides are insulin sensitisers, and they are the preferred initial agent for monotherapy in T2DM. it is most effective in overweight, obese people as it contributes to weight loss. It must be taken with food to reduce stomach and bowel ADRs
MOA
Metformin inhibits mitochondrial respirtation and increases amp/atp ration, which activates hepatic and muscle AMPK which is a cellular signal that the cell needs more energy. this inhibits hepatic gluconeogenesis, increases insulin mediated peripheral glucose uptake in muscle and fat, and increases enterocyte glucose use.
As it increases the amount of lactate at the detriment of pyruvate, there is more lactate in blood, which can be bad for weakened kidneys. it also enhances glucose uptake in skeletal muscle, but the greatest effect is in the GI tract and liver
These are generally helpful
Insulin secretagogues (gliclazide, glibenclamide)
These are sulphonylureas, which stimulate insulin secretion from pancreatic ß-cells. It is useless in ß-cells which do not function. it is ineffective in insulin resistance, may be ineffective in obesity and hypoglycaemic events may occur.
GLP-1 receptor agonists (dulaglutide, wegovy, ozempic, etx)
These are GLP-1 agonists and other molecules in this family.
These are a components of the incretin effect, which is when eating and waiting for food releases the incretin effect which in turn leads to reduced glucagon. Just remember that this leads to greater insulin release following oral vs iv glucose due to incretins.
Incretin hormones include:
- Glucose-dependent insulotropic peptide (GIP)
- Glucagon like peptide-1 (GLP-1)
MoA for insulin release
Incretins work by binding to the GLP-1 receptor, which increases cAMP levels which increases insulin release
Effects
Incretins do a lot, here is a list,
- enhances glucose dependant insulin secretion.
- Helps delay and regulate gastric emptying
- reducing peak BGC
- Promotes satiety and reduced appetite
- Reduces postprandial glucagon secretion
- This in turn decreases hepatic glucose output
- Provides cardiac benefits
Metabolisis
Incretins are metabolised via the DPP-4 enzyme, which can be inhibitor be vildagliptin
levels of GLP-1 in disease and adressing this
the levels or response to GLP-1 can be reduced in disease, such as diabetes which leads to both reduced levels, and in T2DM inpaired response to GIP and GLP-1.
We can increase this by using, 1. using GLP-1 receptor agonists, or 2. using DPP-IV inhibitors.
Dulaglutide
This is recombinant synthetic analogue of exendin-4 which was isolated from salivary gland venom of the gila monster.
It is resistant to degradation of endogenous DPP-4
Administration
This is a once weekly microsphere couples formulation with a half life of 5 days You need to start with a low dose and uptitrate
ADRS
- GI adrs include nausea, vomiting, sulfur burps, and diarrhoea.
- acute pancreatitis, pasopharygitis, needle site reactions.
interactions present with insulin secretagogues and insulin.
DPP-4 inhibitors (Vildagliptin)
These are drugs which inhibit the enzyme which breaks down GLP-1s. This has the effect of increasing their effects.
use wutg metformin
SGLT2 inhibitors(Empagliflozin)
These inhibit the transporters in the kidneys which resorb glucose from the filtrate. This leads to glucose being in the urine which means you lose more glucose on a daily basis, however it leads to higher chance of uti. it will also decrease blood pressure which is good for heart failure.