SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitor) as you can tell from the name this group of medications inhibits sodium-glucose transport proteins in the nephron. in practice they are known as gliflozins or flozins. the biggest metabolic effect is to inhibit the reabsorption of glucose in the kidneys therefore lowering blood sugar. they inhibit the sodium/glucose cotransporter 2. these meds are used in the treatment of type 2 diabetes. besides from blood sugar control, flozins have shown to provide cardiovascular benefit in patients with type 2 diabetes. in studies on one of the flozins, canagliflozin (Ivokana) was found to enhance blood sugar control as well as reduce weight and both systolic and diastolic blood pressure. the american diabetes association (ADA) in 2022 included SGLT2 inhibitors as first line therapy for type 2 diabetes in patients with chronic kidney disease, heart failure of cardiovascular diesease. now lets go over the actual drugs and their names - i usually only go over drugs that are on the canadian market as those are the ones i will see in pharmacy practice. theres canagliflozin (Ivokana) from eariler, dapagliflozin (Forxiga), and empagliflozin (Jardiance) which i fill at least once a day. now MOA! the sodium glucose cotransporters are proteins found in the kidneys as mentioned before, they play an important role in managing glucose balance in the blood. both SGLT1 and SGLT2 are the most known in that class. SGLT2 is the major transport protein and promotes reabsorption from the glomerular filtration glucose back into circulation, its responsible for about 90% of the kidneys glucose reabsorption. it's mainly expressed in the kindeys on the epithelial cells lining the first section of the proximal convoluted tubule. by inhibiting SGLT2, flozins prevent the kidneys reuptake of glucose from the glomerular filtrate and lowers the glucose levels in the blood, and the excretion of the glucose comes out in the urine aka glucosuria. dapagliflozin is a highly competitive and selective inhibitor of SGLT. it's activity is based on each patients blood sugar control and kidney function. this results in decreased kidney reabsorption of glucose, glucosuria increases with higher levels of glucose in the blood circulation. it reduces the blood glucose concentration with a mechanism independent of insulin secretion unlike other antidiabetic medications. functional pancreatic beta cells are not needed for the activity of this medication so it's very helpful for patients with diminished beta cell function. as said before sodium and glucose are co-transported by SGLT2 protein into the tubular epithelial cells across the membrane border of the proximal convoluted tubule which is the segment of the nephron in the kidneys which starts at the renal (tubular) pole of the Bowmans capsule to the beginning of the loop of Henle. this occurs because of the sodium gradient between the tubule and the cell therefore provides a secondary active transport of glucose. it is then later reabsorbed by the passive transfer of endothelial cells in the interstitial glucose transporter protein. SGLT2 is expressed in the human tissues of the kidney, brain, liver, thyroid, muscle and heart. canagliflozin has a bioavailability of 65% from a 300mg dose, t-max of 1-2 hours and its half life of 10.6 hours from a 100mg dose and 13.1 hours from a 300mg dose, the cmax (maximum serum concentration that a drug achieves in a certain area of the body after the drug has been administered and before the administration of a second dose) is 1096 ng/mL from a 100mg dose and 3480 ng/mL from a 300mg dose. for dapagliflozin it's bioavailability is 78%, tmax is 1-1.5 hours, half life of 12.9 hours and cmax of 79.6 ng/mL from a 5mg dose and 165.0 ng/mL from a 10mg dose. last is empagliflozin which has a 90-97% bioavailability in mice, 89% in dogs and 31% in rats, the tmax is 1.5 hours, half life is 13.2 hours for a 10mg dose and 13.3 hours from a 25mg dose. its cmax is 259nmol/L from a 10mg dose and 687nmol/L from a 25mg dose. from studies where dapagliflozin was given to patients iwth type 2 diabetes and non-diabetics in either single ascending dose (SAD) or multiple ascending dose (MAD) showed that a pharmacokinetic profile existed. with dose-dependent concentrations the half life is around 12-13 hours and the tmax of 1-2 hours as well it being protein-bound, the medication has a rapid absorption rate and minimal excretion by the kidney.
DPP-4 inhibitor (Dipeptidyl peptidase) also known as gliptins are a drug class of oral hypoglycemics (decreases blood sugar) that blocks the dipeptidyl peptidase-4 enzyme. they are used for type 2 diabetes. glucagon which is a peptide hormone that is produced in a-cells inside the pancreas is responsible for increasing blood glucose aka blood sugar levels. this drug reduces both the glucagon and blood glucose levels. they want to increase incretin which is a group of peptide metabolic homone that decreases blood glucose levels, which therefore inhibits the glucagon release and then that increases insulin secretion while decreasing gastric emptying and blood glucose levels. now for the drugs themselves, i've filled sitagliptin (Januvia) a lot at work. there's also linagliptin (Trajenta in canada but Tradjenta elsewhere) and saxagliptin (onglyza) but i only really fill sitagliptin the most.
DPP-4 inhibitors and GLP-1