prandin generic name
Type 2 diabetes is a well recognised cause of chronic renal failure (CRF). Only few oral antidiabetic drugs can be used for treating type 2 diabetes in patients with CRF. Among them are repaglinide, a rapid-acting prandial insulin releaser, and peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, such as rosiglitazone and pioglitazone. These compounds are metabolised in the liver, therefore accumulation of the drug and the risk of severe and prolonged hypoglycaemia are minimised. PPARgamma receptors are expressed in many tissues including the kidney. Recently, numerous healthful effects of PPARgamma agonists on several aspects related to renal function have been increasingly reported. These drugs have shown to possess many advantageous anti-inflammatory, haemodynamic, vascular and metabolic effects. In the present paper we have reviewed the more recent experimental studies that evaluated these potential beneficial effects of PPARgamma agonists on renal function and revised the results of their utilisation in patients with different degrees of renal impairment, in dialysis patients, and in patients with diabetes mellitus after kidney transplantation. Finally, tolerability and safety profile of PPARgamma agonists in patients with reduced glomerular filtration rate are also analysed.
prandin generic available
In this 26-week, multicentre, open-label, parallel-group trial, subjects poorly controlled with mono- or dual-oral antidiabetic therapy were randomized 1 : 1 : 1 to receive a repaglinide/metformin FDC tablet either two times daily (BID) or three times daily (TID) or a rosiglitazone/metformin FDC tablet BID. The primary objective comprised two hypotheses tested in a hierarchical order: (i) that treatment with the repaglinide/metformin FDC BID is non-inferior to that of a rosiglitazone/metformin FDC tablet BID as measured by changes in haemoglobin A1c (HbA1c) (results presented here) and (ii) if true, that treatment with the repaglinide/metformin FDC BID was non-inferior to that of the repaglinide/metformin FDC TID as measured by changes in HbA1c (results presented in a companion paper). Additional efficacy and safety end-points were also assessed.
prandin generic form
Data on the serum lipid effects of sulphonylureas, repaglinide, nateglinide and miglitol were inconclusive. Acarbose increased HDL-C and decreased LDL-C and voglibose reduced TC. Metformin at higher doses reduced TC; data on its effects on other lipids were inconclusive. Rosiglitazone increased LDL-C, HDL-C and TC and reduced FFAs but had no effect on TGs. Pioglitazone increased HDL-C and reduced TGs and FFAs but did not affect LDL-C or TC.
In addition to dietary and lifestyle changes, standing as the cornerstone of type 2 diabetes care, pharmacological treatments, whether as single or multidrug patterns, are often necessary for an efficient blood glucose control. Besides insulin, four different oral antidiabetic drug categories are available, each of them acting through different and potentially synergistic ways. Oral antidiabetic drugs include: 1) biguanides acting through the reduction of hepatic glucose production and are most efficient in obese patients; 2) alpha-glucosidase inhibitors delaying carbohydrate intestinal absorption; 3) thiazolidinediones or "glitazones", acting as insulin sensitizers; 4) insulin secretion enhancers, mainly including sulfonylureas, which increase insulin secretion and are being credited by a long clinical usage; these are now joined by the new generation of insulin secretion enhancers, led by repaglinide, which can mimic the physiological insulin secretion profile by a specific stimulatory effect on beta-cells characterized by its fast onset and short half-life. Obviously, the combination of these different antidiabetic drugs, by targetting different synergistic and additive pathways, can help to further improve blood glucose.
prandin tablets generic
Interindividual variability in activity of uptake transporters is evident in vivo, yet limited data exist in vitro, confounding in vitro-in vivo extrapolation. The uptake kinetics of seven organic anion-transporting polypeptide substrates was investigated over a concentration range in plated cryopreserved human hepatocytes. Active uptake clearance (CL(active, u)), bidirectional passive diffusion (P(diff)), intracellular binding, and metabolism were estimated for bosentan, pitavastatin, pravastatin, repaglinide, rosuvastatin, telmisartan, and valsartan in HU4122 donor using a mechanistic two-compartment model in Matlab. Full uptake kinetics of rosuvastatin and repaglinide were also characterized in two additional donors, whereas for the remaining drugs CL(active, u) was estimated at a single concentration. The unbound affinity constant (K(m, u)) and P(diff) values were consistent across donors, whereas V(max) was on average up to 2.8-fold greater in donor HU4122. Consistency in K(m, u) values allowed extrapolation of single concentration uptake activity data and assessment of interindividual variability in CL(active) across donors. The maximal contribution of active transport to total uptake differed among donors, for example, 85 to 96% and 68 to 87% for rosuvastatin and repaglinide, respectively; however, in all cases the active process was the major contributor. In vitro-in vivo extrapolation indicated a general underprediction of hepatic intrinsic clearance, an average empirical scaling factor of 17.1 was estimated on the basis of seven drugs investigated in three hepatocyte donors, and donor-specific differences in empirical factors are discussed. Uptake K(m, u) and CL(active, u) were on average 4.3- and 7.1-fold lower in human hepatocytes compared with our previously published rat data. A strategy for the use of rat uptake data to facilitate the experimental design in human hepatocytes is discussed.
Most patients with type 2 (non-insulin-dependent) diabetes mellitus require pharmacotherapy, initially as monotherapy and subsequently in combination, as adjuncts to diet and exercise. Exogenous insulin is ultimately required in a substantial proportion, reflecting the progressive natural history of the disease. Sulphonylureas and biguanides have been employed for over 4 decades as oral antidiabetic agents, but they have a limited capacity to provide long term glycaemic control and can cause serious adverse effects. Thus, more efficacious and tolerable antidiabetic agents are required. Recent years have witnessed the introduction of agents with novel modes of action, that is, the alpha-glucosidase inhibitors acarbose and miglitol (which reduce postprandial hyperglycaemia) and the first of the thiazolidinedione insulinsensitising drugs--troglitazone and rosiglitazone. Although the former has been withdrawn in some countries due to adverse effects, another 'glitazone' pioglitazone is expected to be approved in the near future. Other recently introduced drugs include glimepiride and the meglitinide insulin secretagogue, repaglinide. Attention is also focusing increasingly on combination therapy using insulin together with sulphonylureas, metformin or troglitazone. Rapid-acting insulin analogues are now being used as alternatives to conventional insulins; their role in the management of type 2 diabetes mellitus is presently uncertain but reports of a reduced frequency of hypoglycaemia are encouraging. The development of new drugs aims to counter the principal metabolic defects of the disorder, respectively, relative insulin deficiency and insulin resistance. Novel classes of rapid-acting secretagogues under evaluation include the morphilinoguanide BTS 67582 and the meglitinides mitiglinide (KAD 1229) and senaglinide (A-4166). Succinate ester derivatives represent a potential novel approach to improving beta-cell function through enhancement of insulin biosynthesis and secretion. Enhancement of nutrient-induced insulin secretion is a mechanism with several putative targets within the beta-cell; potentiators of insulin secretion include glucagon-like peptide-1 and its analogues, phosphodiesterase inhibitors and the imidazoline derivative PMS 812 (S 21663). The amylin agonist pramlintide slows gastric emptying and suppression of glucagon secretion. Non-thiazolidinedione insulin-sensitising agents include the gamma-receptor agonist G 1262570X (GG 570) and D-chiro-inositol. Insulin analogues with prolonged action and inhaled insulin preparations are also under investigation. Insulin-mimetic agents include organic vanadium compounds. Whether newer agents will offer clinically relevant efficacy and tolerability advantages over existing therapies remains to be determined.
prandin generic price
Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes.
Significant dose-related increases in early insulin secretion were found only in less advanced diabetic subjects. In advanced diabetic patients, only the maximum dose (4 mg) was significant compared with placebo. Better proinsulin-to-insulin processing was noted with increasing drug doses.