Which of the following does not act by increasing insulin secretion?
Ans. a. Rosiglitazone (Ref: Harrison 18/e p2998, 17/e p2300; KDT 7/p270, 6/e p269,270; Goodman Giilman 12/e p1260; Katzung 12/e p757, Katzung 11/e p742,743)Rosiglitazone does not act by increasing insulin secretion. Rosiglitazone is an oral antihyperglycemic agent that acts primarily by decreasing insulin resistance."Rosiglitazone is an oral antihyperglycemic agent that acts primarily by decreasing insulin resistance. It deceases insulin resistance in the muscles, adipose tissues and in the liver resulting in increased insulin dependent glucose disposal and decreased hepatic glucose output. ""Pioglitazone and rosiglitazone are insulin sensitizers and increase insulin-mediated glucose uptake by 30-50% in patients with type 2 diabetes. Although adipose tissue seems to be the primary target for PPARg agonists, both clinical and preclinical models support a role for skeletal muscle, the major site for insulin-mediated glucose disposal, in the response to thiazolidinediones. In addition to promoting glucose uptake into muscle and adipose tissue. the thiazolidinediones reduce hepatic glucose production and increase hepatic glucose uptake. "--Goodman Giilman 12/e p1260"Thiazolidinediones (Tzds) act to decrease insulin resistance. Tzds are ligands of peroxisome proliferator-activated receptor- gamma, part of the steroid and thyroid superfamily of nuclear receptors. These PPAR receptors are found in muscle, fat, and liver. "--Katzung 12/e p757Anti-hyperglycemic DrugsOralParenteralInsulin Secretagogues (Increase Insulin Secretion)InsulinSulfonylureas* 1st Generation:- Tolbutamide,Chlorpropamide* 2nd Generation:- Glibenclamide, Glipizide- Gliclazide, GlimepirideUltra short acting* Lispro, Aspart, GlulisineShort acting* Regular (Crystalline zinc) * Semi lenteIntermediate Acting* NPH, LenteLong Acting* Glargine, DetemirNewer generation* Albulin, Inhaled insulinMeglitinides* Repaglinide, NateglinideQ* GLP-1 analogs: ExenatideQ, LiraglutideQ* Amylin analogues: PramlintideQDipeptidyl Peptidase-4 inhibitors* Sitagliptin, VildagliptinQ* Saxagliptin, AlogiiptinQ* LinagliptinQOther Mechanisms Overcome insulin resistance* Biguanides: MetforminQ* ThiazolidinedionesAlpha-glucosidaseinhibitors* Acarbose, MiglitolQ* VagliboseQSodium glucose Contransporter-2 (SGLT-2) inhibitors* Dapaglifozin* Serglifozin* Remoglifozin* Canaglifozin RosiglitazoneBelongs to Thiazoiidinedione's; Other drugs of this group are Troglitazone. Pioglitazone.It is an oral antihyperglycemic agent that acts primarily by decreasing insulin resistanceQRosiglitazone deceases insulin resistance in the muscles, adipose tissues and in the liver resulting in increased insulin dependent glucose disposal and decreased hepatic glucose outputQMechanism of action:Potent and highly selective agonist for peroxisome proliferator activated receptor gamma (PPARg)QPPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle and liver (highest level in adipose tissue).Activation of (PPARg) nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose & lipid metabolismQ.Rosiglitazone appears to reduce insulin resistance by enhancing fatty acids storage and possibly by increasing adiponectin levelsQMetabolism:Extensively metabolized in liver by hydroxylation & oxidationQLiver function should be monitored in patients receiving thiazoiidinedione's even though pioglitazone & rosiglitazone rarely have been associated with hepatotoxicity.Thiazolidinedione's should not be used in patients with NYHA class III or IV failure.Main side effect of all thiazolidinedione's is water retention leading to edema.Sometimes there is significant water retention leading to decompensation of potentially previously unrecognized heart failureThiazolidinedione's should be prescribed with both caution and patient warnings about the potential for water retention/weight gain especially in patients with decreased ventricular function.Adverse Effect:Rosiglitazone increases the risk of angina & Ml
Rosiglitazone
Repaglinide
Exenatide
Sitagliptin
Anti Diabetes