B.19 Flashcards
Oral antidiabetics
- Biguanides: Metformin
- DPP-4-I: Vildagliptin
- SGLT2-I: Dapagliflozin
- SUR: Gliclazide, Glimepiride
- Meglitinides: Repaglinide
- TDZ: Thiazolidinediones (pioglutazone)
Body weight effect of oral antidiabetics
Body weight ↓: Metformin, SGLT-2 Inhibitor, GLP-1/GIP analogues
Body weight not changing: Metformin, DPP-4 inhibitors
Body weight ↑: Sulfonylureas, Meglitinides, TZDs, Insulin
Hypoglycemia risk
Low: TZD, GLP-1/GIP analogues, AGI, DPP-4 Inhibitor, Metformin
Moderate: SGLT-2 inhibitors
High: SU, Meglitinides, Insulin
GLP-1 (glucagon-like peptide 1) effects
Enhance insulin release →this effect is preserved in T2DM
Reduced glucagon secretion
Secreted in the ileum and colon
GIP (gastric inhibitory polypeptide)
Enhance insulin release- might be lost in T2DM
Secreted in duodenum and jejunum
Metformin
Structure: Biguanide;
MOA: AMPK-pathway enhancement (→ ↓gluconeogenesis in the liver, ↓TAG levels, ↓Glucagon synthesis, ↓Glucose absorption in the gut, ↑Glucose uptake in the muscles, Antioxidant effect, Weight loss effect, ↑↑Insulin sensitivity!!);
IND: T2DM (1st line!), can be considered in- Polycystic ovarian syndrome and Diseases associated with hyperinsulinemia/insulin resistance;
SEs: GI (nausea, vomiting, lack of appetite, metallic taste, diarrhea), disturbances with vit. B12 absorption→megaloblastic anemia (possible mechanism: altered microbiom and gut motility, reduced uptake of intrinsic factor-B12 complex interminal ileum), Lactic acidosis (metformin-induced/associated lactic acidosis);
Contra-IND: Acute metabolic acidosis, Severely reduced renal function (GFR<30mL/min), Acute conditions that indirectly impair renal function (e.g. dehydration), Conditions causing tissue hypoxia (e.g. respiratory/circulatory failure, MI), Liver failure, Alcoholism, with iodine contrast agents
Dapagliflozin
MOA: SGLT-2 inhibitor→↑Glucose secretion in the kidney, ↓Plasma glucose levels (renal glucose reabsorption in the proximal tubules is reduced), beneficial b/c SGLT-2 expression is increased in T2DM, minor effect on SGLT-1;
Effects: effect independent of pancreas function, Weight loss, Beneficial cardiovascular effects (can be used in HF without T2DM);
SEs: Renal function-dependent effect (→insufficient therapeutic effect with low GFR), Polyuria, dehydration, reduced BP, hypoglycemia, Euglycemic ketoacidosis, Glucose secretion in urine (→ risk of UTI↑, gynecological infections↑)
Vildagliptin
MOA: DPP-4 inhibitor (inhibition of incretin degradation enzyme→ enhancing incretins effects→enhancing insulin effects)→ glucose dependent effect, hypoglycemia is low risk, no change in body weight;
SEs: Nasopharyngitis, Headache, nausea, Pancreatitis and pancreas tumurs;
IND: oral antidiabetic
Acarbose
MOA: α-Glucosidase inhibitor (AGI) →inhibition of the enzyme that degrades disaccharides (α-glucosidase) →↓Carbohydrate abs., ↓Postprandial hyperglycemia, Beneficial in obese patients, BUT! doesn’t inhibit lactose degradation in lactase-persistent patients;
SEs: Bloating, Abdominal pain, Flatulence, Diarrhea (→due to the interaction btw non-absorbed sugars and intestinal flora);
IND: oral antidiabetic
Glipizide, Glimepiride, Gliclazid
MOA: sulfonylureas, SUR (ATP sensitive K+) channel inhibition (→relative depolarization and Ca2+ signal lead to insulin release, Glucagon levels ↓ due to insulin influx), Potent active substances, Pancreas selective; IND: oral antidiabetics;
SEs: Hypoglycemia, Hyperinsulinemia (leading to overeating and weight gain), Hematological abnormalities (e.g. thrombocytopenia)
Repaglinide
MOA: SUR (ATP sensitive K+) channel inhibition (mechanism identical to sulfonylureas, but no sulfa group);
Kinetics: faster action than sulfonylureas;
IND: oral antidiabetic, Prevent postprandial blood glucose surges (should be taken before meals);
SEs: Hypoglycemia (less severe than sulfonylureas)
