Glucose Lowering Agents Flashcards
For what disease are the glucose-lowering drugs (aside from insulin)?
Type 2 diabetes.
they don’t work for T1D
What 4 organs that are targeted by glucose-lowering drugs? What is the goal of drugs targeting these organs?
Liver - decrease gluconeogenesis
Pancreas - increase insulin secretion, decrease glucagon secretion/signaling
Skeletal muscle - increase glucose uptake (insulin sensitivity)
Gut - decrease carb absorption, increase incretins
What are 4 advantageous effects that you want in glucose lowering drugs?
Weight neutral or causes weight loss.
Does not cause hypoglycemia.
Infrequent administration.
Oral administration (instead of injection).
3 ways glucose-modifying drugs can cause weight gain?
Reversal of osmotic diuresis.
Reversing “relative starvation.”
Causing water retention.
Biguanides: What’s the most notable one? MoA?
Adverse effects?
Efficacy?
Metformin.
MoA: activate AMPK, reduce gluconeogenesis in liver (also increases liver insulin sensitivity?)
Adverse effects: Anorexia/nausea/diarrhea, lactic acidosis. (slowly increase dose to avoid these effects)
Efficacy: Lowers A1c up to 2 percentage points.
What is an insulin secretogogue? What are 2 drug classes that do this?
Insulin secretogogues induce pancreas to secret insulin.
Sulfonylurea.
Meglitinides/glinides.
Sulfonylurea MoA?
Notable contraindications?
Adverse effects?
In beta cells, sulfonylurea closes ATP-dependent (i.e. ATP-inhibited) K+ channels -> depolarization (more positive membrane voltage) –> insulin release. Acts for 12-24 hrs.
Notable contraindications include DKA (because there’s no insulin to promote the release of), renal impairment (it’s metabolized renally).
Adverse effects: Hypoglycemia, hunger, weight gain (because there’s more insulin).
Note that meglitinides and sulfonylureas have about the same MoA. What’s the main difference between sulfonylurea and meglitinides?
Meglitinides are shorter-acting (3-4 hours). Taken before meals, but can cause post-prandial hypoglycemia.
Thiazolidinedione effect? MoA?
Effect: Sensitizes muscle, adipose, liver to glucose (more glucose uptake).
MoA: Binds PPAR-gamma nuclear receptor -> increased transcription of GLUT-4.
Good things about thiazolidinedione? Bad things?
Good: Doesn’t cause hypoglycemia. Relatively effective (can lower A1c by about 1.8 percentage points).
Bad: Causes hypervolemia -> bad when pt has renal failure or heart disease. Also rough on liver.
What do alpha-glucosidase inhibitors do?
Adverse effects?
Delay absorption of carbs from gut, and increase GLP-1 response to feeding.
Flatulence, bloating. (probably like lactose intolerance: if you don’t eat it, your GI flora will, and make gas)
Review: Where are GLP-1 and GIP made?
The gut. (specifically, mostly in the distal ileum)
3-4 effects of GLP-1?
Increases insulin, decreases glucagon.
Slows gut motility.
Induces satiety.
Why do GLP-1 / GIP have such short half-lives?
They’re degraded by peptidases in the small intestine.
What do Gila monsters have to do with diabetes treatment?
Their (poisonous) saliva contains a GLP-1 analogue, exanetide, that has a longer half-life than GLP-1 and can be given subcutaneously.
