<prompt> Which of the following does not act by increasing insulin secretion?RosiglitazoneRepaglinideExenatideSitagliptin  <response>: Ans. a. Rosiglitazone Ref: Harrison 18e p2998, 17e p2300; KDT 7p270, 6e p269,270; Goodman Giilman 12e p1260; Katzung 12e p757, Katzung 11e p742,743Rosiglitazone 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 12e p1260Thiazolidinediones 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 12e p757Anti-hyperglycemic DrugsOralParenteralInsulin Secretagogues Increase Insulin SecretionInsulinSulfonylureas 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 Thiazoiidinediones; 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 PPARgQPPAR 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 thiazoiidinediones even though pioglitazone rosiglitazone rarely have been associated with hepatotoxicity.Thiazolidinediones should not be used in patients with NYHA class III or IV failure.Main side effect of all thiazolidinediones is water retention leading to edema.Sometimes there is significant water retention leading to decompensation of potentially previously unrecognized heart failureThiazolidinediones should be prescribed with both caution and patient warnings about the potential for water retentionweight gain especially in patients with decreased ventricular function.Adverse Effect:Rosiglitazone increases the risk of angina Ml 