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the best possible metabolic control is that which prevents and&#47;or slows the progressive evolution of the disease&#44; while also acting on other progression factors such as arterial hypertension&#44; albuminuria&#44; tobacco use&#44; and obesity&#46; The treatment objectives for glycaemic control tend to be expressed in terms of a target glycosylated haemoglobin values &#40;HbA<span class="elsevierStyleInf">1c</span>&#41; &#60;7&#37;&#46;<span class="elsevierStyleSup">2</span> In order to achieve this optimal control&#44; two primary obstacles must be surpassed&#58; the inconvenience of administering certain glucose-lowering drugs that are contraindicated in CKD&#44; and the predisposition towards hypoglycaemia in these patients&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">A&#41; Oral anti-diabetic drugs</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Classification of oral anti-diabetic drugs</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Oral anti-diabetic drugs &#40;OAD&#41; are classified into&#58;</p><ul><li>Insulin secretagogue drugs &#40;Table 1&#41;&#58; sulfonylureas&#44; meglitinides&#44; dipeptidyl-peptidase 4 inhibitors &#40;iDPP4&#41;&#46;</li><li>Drugs that stimulate the peripheral activity of insulin&#58; metformin&#44; pioglitazone&#46;</li><li>Drugs that inhibit &#945;-glycosidase in the intestines &#40;delay the absorption of glucose&#41;&#58; acarbose&#44; miglitol&#46;</li></ul><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">General characteristics of the primary groups of oral anti-diabetic drugs</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Sulfonylureas&#58;<span class="elsevierStyleItalic"> </span></span>These drugs are capable of stimulating<span class="elsevierStyleItalic"> </span>&#946;-cells in order to increase endogenous secretion of insulin&#46; Sulfonylureas are contraindicated in patients with renal failure&#46; Their main secondary side effects include hypoglycaemia&#44; which can be severe&#44; and weight gain&#46;<span class="elsevierStyleItalic">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Meglitinides &#40;repaglinide and nateglinide&#41;&#58;</span> Both of these drugs have a short half-life&#44; and so are administered before each meal&#46; Repaglinide is more potent&#44; and is primarily eliminated in the bile&#44; making its use acceptable in any stage of CKD&#44; even in patients on dialysis&#46; Nateglinide&#44; despite being metabolised in the liver&#44; is degraded into active metabolites that are filtered out in the kidneys&#44; making this drug unadvisable in patients with CKD&#46; Both drugs can produce hypoglycaemia&#44; although this condition is produced less frequently than with sulfonylureas because of the shorter half-lives&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Metformin&#58;</span> Metformin is a biguanide whose primary mechanism of action is reducing the level of glucose production in the liver by acting on gluconeogenesis&#44; although it also increases muscle uptake of glucose&#46; It is eliminated by the kidneys&#44; and so the technical data sheet contraindicates its use in patients with creatinine clearance &#60;60ml&#47;min due to the risk of lactic acidosis&#46; In fact&#44; it can be used up to a glomerular filtration rate &#40;GFR&#41; of 30ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span> &#40;see explanation below&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Glitazones&#58; </span>Rosiglitazone was removed from the market due to the possibility of increased cardiovascular risk&#46; Its primary mechanism of action is to increase the body&#8217;s sensitivity to insulin by increasing the uptake and use of glucose in muscle and fat tissue&#46; It also decreases&#44; to a lesser degree&#44; gluconeogenesis and the synthesis of fatty acids in the liver&#46; It is metabolised in the liver and excreted in faeces&#44; and so can be used in any stage of CKD&#46; Its association with weight gain&#44; which is due to water retention&#44; has led to the contraindication against its use in patients with heart or liver failure&#44; and the possibility of distal fractures in women must also be taken into account&#46; In France and Germany&#44; pioglitazone has been removed from the market due to the possibility of increased risk of bladder cancer&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#945;-Glycosidase inhibitors &#40;acarbose and miglitol&#41;&#58; </span>Produce a competitive and reversible inhibition of &#945;-glycosidase in the intestinal microvilli&#44; delaying the absorption of complex carbohydrates and decreasing the post-prandial glycaemic peak&#46; In monotherapy&#44; these drugs do not increase weight or hypoglycaemia&#46; They are contraindicated in severe CKD&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dipeptidyl-peptidase 4 inhibitors&#58; </span>These drugs intensify the activity of incretin by inhibiting the enzyme dipeptidyl-peptidase IV&#44; which degrades glucagon-like peptide 1 &#40;GLP-1&#41;&#44; which is produced in the intestines in response to eating&#46; GLP-1 stimulates the secretion of insulin and inhibits the secretion of glucagon&#46; In this manner&#44; these drugs produce a physiological secretion of insulin mediated by food intake&#44; and an inhibition of excessive glucagon&#46; The iDPP4 that have been commercialised in Spain currently include&#58; sitagliptin&#44; vildagliptin&#44; saxagliptin&#44; and linagliptin&#46; This group of drugs provides major advantages over classically used secretagogues&#44; since they do not produce hypoglycaemia&#44; by using an insulin secretion stimulation mechanism that is not dependent on glucose levels&#44; a characteristic that makes these drugs especially attractive in patients with CKD due to the predisposition of these patients to developing hypoglycaemia&#46;</p><p class="elsevierStylePara">Sitagliptin&#44; vildagliptin&#44; and saxagliptin require dosage adjustments&#44; since the elimination of these drugs is essentially through the kidneys&#46; Recent studies with linagliptin have shown that this drug is eliminated by the liver and bile&#44; and that its half-life extends to a maximum of 14-18 hours in patients with advanced CKD&#44; obviating the need for dosage adjustments&#46; This drug has even been used in diabetic patients on haemodialysis&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Oral anti-diabetic drugs in patients with chronic kidney disease who are not on dialysis</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Table 2 summarises the indications for the different therapeutic groups of oral anti-diabetic drugs for use in chronic kidney disease&#44; and the Figure displays the usage of these different therapeutic groups of oral anti-diabetic drugs and insulin therapy in the different stages of chronic kidney disease&#46;</p><p class="elsevierStylePara">For proper management of hyperglycaemia&#44; the American Diabetes Association &#40;ADA&#41; and the European Association for the Study of Diabetes &#40;EASD&#41;&#44; in 2008&#44;<span class="elsevierStyleSup">3</span> recommended that all patients with type 2 DM be treated with metformin from the moment of diagnosis&#44; except when formally contraindicated or not tolerated by the patient&#46; Initial treatment with metformin continues to be the recommendation in updated guidelines from both societies<span class="elsevierStyleSup">3&#44;4</span> and this protocol has also been backed by the major Spanish medical societies involved in the treatment of type 2 DM&#46;<span class="elsevierStyleSup">5</span> However&#44; the technical data sheet for metformin displays a contraindication for using the drug when creatinine clearance &#60;60ml&#47;min&#46; The NICE guidelines<span class="elsevierStyleSup">6</span> and recent studies<span class="elsevierStyleSup">7</span> indicate that it can be safely used in patients with creatinine clearance &#62;30ml&#47;min&#44; recommending a dosage reduction when glomerular filtration rate &#40;GFR&#41; &#60;45ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#46; The Food and Drug Administration &#40;FDA&#41; bases its recommendations solely on creatinine concentrations &#40;contraindicating the use of metformin when serum creatinine &#8805;1&#46;5mg&#47;dl in males and &#8805;1&#46;4mg&#47;dl in females&#41;&#46; Recently&#44; a study was published in which metformin was used in patients with creatinine clearance of approximately 20ml&#47;min&#44; with doses of 200-500mg&#47;day&#46;<span class="elsevierStyleSup">8</span> As Lipska et al&#46; suggested&#44;<span class="elsevierStyleSup">9</span> it would appear reasonable to suspend the use of metformin in patients with an estimated GFR &#40;eGFR&#41; &#60;30ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#44; or a GFR&#60;45ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span> in patients with risk factors for developing lactic acidosis &#40;peripheral hypoperfusion&#44; diabetic foot&#44; heart failure&#44; advanced liver disease&#44; or a previous history of lactic acidosis&#41;&#46;</p><p class="elsevierStylePara">Changes to treatment protocols must be made early in order to prevent or delay complications&#44; instating combined treatment regimens early&#46; The technical data sheets for sulfonylurea are contraindicated for patients with severe renal failure &#40;stage 4 or 5 CKD&#41;&#46; In stage 3 CKD&#44; gliquidone&#44; glipizide&#44; and gliclazide can be used&#44; although there is a high risk of hypoglycaemia&#46;</p><p class="elsevierStylePara">Repaglinide is eliminated primarily through the bile&#44; and only 8&#37; is eliminated by the kidneys&#44; making this drug a feasible option in patients with any stage of CKD&#46;<span class="elsevierStyleSup">10</span> However&#44; it is contraindicated when patients are taking gemfibrozil&#44; due to the possibility of an increased risk of hypoglycaemia if the repaglinide dose is not adjusted&#46; In contrast&#44; nateglinide is metabolised by the liver&#44; forming various active metabolites that are eliminated through the kidneys&#46; Metabolisation of this drug through the CYP2C9 may provoke interactions with several different commonly used drugs &#40;amiodarone&#44; warfarin&#41;&#46; Cases of severe hypoglycaemia have been described when administering this drug in patients with kidney disease&#46;<span class="elsevierStyleSup">11</span> This makes it unadvisable to administer this drug in patients with CKD&#46;</p><p class="elsevierStylePara">Few studies have examined the use of iDDP4 in patients with type 2 DM and altered renal function&#44; with a very small number of patients in the case of sitagliptin&#44;<span class="elsevierStyleSup">12&#44;13</span> saxagliptin&#44;<span class="elsevierStyleSup">14</span> and vildagliptin&#46;<span class="elsevierStyleSup">15</span> Sitagliptin&#44; vildagliptin&#44; and saxagliptin require dosage adjustments when creatinine clearance falls below 50ml&#47;min&#44; since these drugs are primarily eliminated by the kidneys&#46; This form of sitagliptin &#40;50mg&#41; is not currently commercially available in Spain&#46; Half doses of saxagliptin &#40;2&#46;5mg&#41; are commercially available&#44; but are not currently subsidised in Spain&#46; One recent study involving 124 patients with type 2 DM and severe CKD &#40;mean eGFR&#58; 21&#46;9&#177;5&#46;7ml&#47;min&#47;ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#41; showed that vildagliptin effectively decreased HbA<span class="elsevierStyleInf">1c</span> levels&#44; and adverse effects were similar to those produced in the placebo group&#46;<span class="elsevierStyleSup">15</span> In the case of vildagliptin&#44; the recommended dose in patients with CKD on dialysis is 50mg&#47;day &#40;1 pill&#41;&#44; instead of every 12 hours&#46; Linagliptin deserves special mention for being the only iDPP4 that is almost exclusively eliminated by the bile&#44; allowing for its use in patients with any stage of CKD&#44; including those on dialysis&#44; without requiring an adjustment of the dosage &#40;Table 3&#41;&#46;<span class="elsevierStyleSup">16</span></p><p class="elsevierStylePara">The group of &#945;-glycosidase inhibitors has limited hypoglycaemic activity&#46; Acarbose is not absorbed for the most part&#46; Miglitol is well absorbed&#44; but not metabolised&#44; and is eliminated by the kidneys with a half-life of 2-3 hours&#46; Plasma concentrations increase in patients with renal failure&#44; and so miglitol is contraindicated in patients with CKD&#46;</p><p class="elsevierStylePara">Pioglitazone can be administered in patients with any stage of CKD&#44; although in severe CKD&#44; one must take precautions due to the possibility of adverse effects &#40;weight gain&#44; oedema&#44; and worsening of heart failure&#41;&#46; This drug does not require dosage adjustments in mild or moderate CKD&#46; In patients with CKD&#44; plasma concentrations of pioglitazone and its metabolites are lower than in individuals with normal renal function&#46; However&#44; clearance of the original substance is similar&#46; As such&#44; the concentration of free pioglitazone remains unaltered&#44; and so its use is not contraindicated in patients with CKD&#46; Pioglitazone can produce fluid retention in mild or moderate cases of CKD&#44; and so this condition should be more closely monitored in patients that might have heart failure&#46; Proper diuretic treatment must also be applied when this drug is used&#46; Pioglitazone is indicated in combined therapy with sulfonylureas&#44; metformin&#44; iDPP4&#44; or insulin&#46; In monotherapy&#44; it is only indicated if treatment with metformin is contraindicated &#40;in the case of mild or severe CKD&#41; or when patients are intolerant to metformin&#46;</p><p class="elsevierStylePara">In the case of patients with CKD and creatinine clearance &#60;30-60ml&#47;min&#44; a combination of iDPP4 or repaglinide &#40;which improve the secretion of insulin in the case of persistent insulin reserve&#41; with pioglitazone &#40;which improves sensitivity to insulin&#41;&#44; can be used only if the patient is not prone to fluid retention&#46; iDPP4 agents present a major advantage over repaglinide by not producing hypoglycaemia&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Oral anti-diabetic drugs in patients with chronic kidney disease on dialysis</span></span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#160;</span></span></p><p class="elsevierStylePara">As GFR decreases&#44; insulin is broken down to a lesser degree&#46; In this situation&#44; patients perceive that they require a lower dose of OAD &#40;which may even be temporarily suspended due to lengthened lifetime of endogenous insulin&#41; or insulin&#46; As such&#44; patients frequently refuse insulin treatment when taking OAD&#46; When receiving insulin&#44; patients may perceive an improvement in the treatment of hyperglycaemia&#46;</p><p class="elsevierStylePara">Sulfonylureas should be avoided in patients on haemodialysis&#46; They bind strongly to albumin&#44; and so high levels of the drug cannot be eliminated through haemodialysis&#46; Simultaneous administration of beta-blockers&#44; aspirin&#44; or dicoumarin increases the proportion of free drug molecules in the blood and can produce severe hypoglycaemia&#46; This situation is less severe with certain sulfonylureas &#40;glipizide and glimepiride&#41;&#46; However&#44; there are not recommended in a patients on haemodialysis&#46;</p><p class="elsevierStylePara">Glitazones are associated with a high risk of oedema and heart failure&#44; which increases as GFR decreases&#46; As such&#44; their use is not recommended in patients on dialysis&#44; although they can be used in patients with advanced CKD&#46; Since repaglinide is metabolised in the liver&#44; it can be used in these patients&#44; although with strict monitoring in light of the high risk of hypoglycaemia&#46; Treatment must be started with a minimal dosage &#40;0&#46;5mg&#41; and subsequently&#44; dosage must be carefully monitored&#46; Recently&#44; positive results were published from a study in which hyperglycaemia was treated with vildagliptin in patients with type 2 DM on haemodialysis&#44; with no secondary side effects or hypoglycaemia produced&#46;<span class="elsevierStyleSup">17</span> Linagliptin can be used in dialysis patients because it is almost exclusively eliminated by the bile&#46; However&#44; insulin treatment continues to be the treatment of choice in patients on dialysis&#44; both haemodialysis and peritoneal dialysis&#46; Undoubtedly&#44; further research into the management of new iDPP4 in patients with advanced CKD or on dialysis will provide us with new perspectives for managing hyperglycaemia in these patients&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">B&#41; Insulin therapy</span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#160;</span></span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Dosage adjustments for insulin in patients with chronic kidney disease not on dialysis</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Chronic renal failure is associated with a decrease in renal catabolism of insulin&#46; As such&#44; glycaemia levels in diabetic patients with renal failure on treatment with insulin must be closely monitored and adjusted for personalised treatment&#46; However&#44; certain general guidelines have been established for dosing insulin treatment in these patients<span class="elsevierStyleSup">18&#44;19</span>&#58;</p><p class="elsevierStylePara">- Dosage does not require adjustments if GFR is &#62;50ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#46;</p><p class="elsevierStylePara">- The dose of insulin should be reduced by 25&#37; when GFR is between 10ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span> and 50ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#46;</p><p class="elsevierStylePara">- The dose of insulin should be reduced by 50&#37; when GFR is &#60;10ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Subcutaneous insulin regimens in patients on dialysis</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In haemodialysis&#44; as in diabetic patients without renal failure&#44; several different regimens of insulin therapy can be used&#44; such as premixed insulin 2-3 times per day or baseline bolus prescriptions &#40;slow-acting insulin along with fast-acting insulin before meals&#41;&#46;<span class="elsevierStyleSup">20&#44;21</span> Although there is no single regimen recommended for these patients&#44;<span class="elsevierStyleSup">19</span> insulin analogues are preferable over human insulin&#44; since analogues have shown to produce hypoglycaemia at a lower rate&#46; As such&#44; basal analogues &#40;glargine&#44; 1 per day&#44; or detemir&#44; 1-2 times per day&#41; are preferred over NPH insulin &#40;neutral protamine hagedom&#41;&#44; and fast-acting analogues &#40;lispro&#44; aspart&#44; and glulisine&#41; are preferred over regular insulin &#40;Table 4&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Intraperitoneal insulin in patients on peritoneal dialysis</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In diabetic patients&#44; peritoneal dialysis fluid solutions are recommended to have low glucose content or none at all&#44; such as those based on amino acids or glucose polymers&#46; Insulin can be administered subcutaneously or directly into the peritoneum&#44; by introducing insulin into peritoneal dialysis boluses just before infusion into the peritoneum&#46; If only the traditional subcutaneous route is used&#44; 2 different doses of premixed insulin must be administered&#44; 1 or 2 doses of slow-action insulin analogues&#44; or even 3 doses of regular insulin together with meals in selected patients&#46; The intraperitoneal approach provides both advantages and disadvantages over the subcutaneous approach&#44; but allows for controlling glycaemia&#44; and so may be the best option for the treatment of very disciplined&#44; self-sufficient patients with motivation for close control of treatment&#46; This administration route is more physiological than the subcutaneous approach&#44; since insulin is absorbed directly in the portal vein as occurs in non-diabetic patients with endogenous insulin&#44; reducing the secondary side effects associated with direct absorption of insulin into systemic circulation&#46; Fast-acting insulin should always be used&#44; and boluses should be administered just prior to infusion&#44; matching up changes of the bolus with major meals&#46; This method requires relatively large needles &#40;3&#46;8cm&#41; in order to ensure the injection of the entire dose of the bolus into the dialysate&#46; This bolus must be inverted on several occasions following injection in order to mix the solution properly&#46;</p><p class="elsevierStylePara">In the case of automated peritoneal dialysis techniques &#40;continuous cyclic peritoneal dialysis or nocturnal intermittent peritoneal dialysis&#41;&#44; in which most of the dialysis sessions are performed at night&#44; intra-peritoneal doses must be added as well as regular insulin whenever patients self-apply dialysis using a cycler&#44; and this administration provides baseline coverage during the night&#46;<span class="elsevierStyleSup">22-24</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">C&#41; GLP-1 analogues</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">GLP-1 agonists bind to the receptors of this hormone&#44; produced in the intestine before the arrival of the food bolus&#44; increasing the secretion of insulin in the pancreas and inhibiting the secretion of glucagon&#46; In addition&#44; they slow gastric emptying and decrease appetite&#44; therefore its use is associated with weight loss&#46; The most common adverse effects of these drugs are nausea and vomiting&#46; The two currently commercially available GLP-1 antagonists for treating type 2 DM are exenatid and liraglutid &#40;Table 5&#41;&#46;</p><p class="elsevierStylePara">Since it is eliminated by the kidneys&#44; exenatid requires dosage adjustments when clearance is 30-50ml&#47;min&#44; and its use is not recommended in patients with stage 4 and 5 CKD &#40;creatinine clearance &#60;30ml&#47;min&#41;&#46;</p><p class="elsevierStylePara">The safety of liraglutid is not well established in patients with CKD&#44; although pharmacokinetic analyses suggest that drug levels in the body are no different in this sub-group&#46;<span class="elsevierStyleSup">25</span> Dosage adjustments for liraglutid are not required in mild CKD &#40;clearance &#62;60ml&#47;min&#41;&#46; Below this level&#44; the extremely scarce experience in stage 3 cases and the lack of experience with patients with stage 4 and 5 contraindicate its use&#46; Currently&#44; these drugs cannot be recommended for use in patients with moderate or severe CKD&#44; including patients with stage 5 CKD&#46;</p><p class="elsevierStylePara">In conclusion&#44; the current management of hypoglycaemic drugs in diabetic patients requires several conceptual modifications&#44; which involves all health care professionals in charge of these patients&#46; When a patient suffers from CKD&#44; we must take into account not only the technical data sheet for anti-diabetic drugs&#44; but also the metabolic pathways of these drugs and their safety profiles&#46; Given the scarcity of studies carried out in patients with CKD that focus on treating hyperglycaemia&#44; the ongoing development of new treatment options&#44; and the high prevalence of diabetes mellitus in these patients&#44; we must prioritise keeping our treatment protocols for hyperglycaemia in patients with CKD constantly updated&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors have no conflicts of interest to declare&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11576&#95;16025&#95;33456&#95;en&#95;t111576i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11576_16025_33456_en_t111576i.jpg" alt="Oral anti-diabetic drugs and their use in chronic kidney disease according to drug technical data sheets"></img></a></p><p class="elsevierStylePara">Table 1&#46; Oral anti-diabetic drugs and their use in chronic kidney disease according to drug technical data sheets</p><p class="elsevierStylePara"><a href="grande&#47;11576&#95;16025&#95;33457&#95;en&#95;t211576i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11576_16025_33457_en_t211576i.jpg" alt="Indications for the different treatment groups of oral anti-diabetic drugs in chronic kidney disease patients"></img></a></p><p class="elsevierStylePara">Table 2&#46; Indications for the different treatment groups of oral anti-diabetic drugs in chronic kidney disease patients</p><p class="elsevierStylePara"><a href="grande&#47;11576&#95;16025&#95;33458&#95;en&#95;t311576i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11576_16025_33458_en_t311576i.jpg" alt="Approved uses of DPP4 inhibitors in renal failure and liver failure &#40;2012&#41;"></img></a></p><p class="elsevierStylePara">Table 3&#46; Approved uses of DPP4 inhibitors in renal failure and liver failure &#40;2012&#41;</p><p class="elsevierStylePara"><a href="grande&#47;11576&#95;16025&#95;33459&#95;en&#95;t411576i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11576_16025_33459_en_t411576i.jpg" alt="Pharmacokinetic characteristics of the different insulin compounds available"></img></a></p><p class="elsevierStylePara">Table 4&#46; Pharmacokinetic characteristics of the different insulin compounds available</p><p class="elsevierStylePara"><a href="grande&#47;11576&#95;16025&#95;33460&#95;en&#95;t511576i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11576_16025_33460_en_t511576i.jpg" alt="Glucagon-like peptide 1 analogues in patients with chronic kidney disease"></img></a></p><p class="elsevierStylePara">Table 5&#46; Glucagon-like peptide 1 analogues in patients with chronic kidney disease</p><p class="elsevierStylePara"><a href="grande&#47;11576&#95;16025&#95;33461&#95;en&#95;f111576i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11576_16025_33461_en_f111576i.jpg" alt="The use of different treatment options involving oral anti-diabetic drugs and insulin in the different stages of chronic kidney disease"></img></a></p><p class="elsevierStylePara">Figure 1&#46; The use of different treatment options involving oral anti-diabetic drugs and insulin in the different stages of chronic kidney disease</p>"
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                  "referenciaCompleta" => "Pozo-Fernández C, Pardo-Ruiz C, Sánchez-Botella C, Blanes-Castañer V, López-Menchero R, Gisbert-Sellés C, et al. Discrepancias entre documentos de consenso, guías, práctica clínica y normativa legal en el tratamiento de los pacientes con diabetes mellitus tipo 2. Nefrologia 2012;32:367-73. <a href="http://www.ncbi.nlm.nih.gov/pubmed/22592422" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holmann RR, Sherwin R, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2008;31:1-11."
                  "contribucion" => array:1 [
                    0 => null
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              "identificador" => "bib6"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "NICE. Type 2 diabetes: the management of type 2 diabetes: NICE clinical guideline 87. National Institute of Health and clinical Excellence, 2009."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
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              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Shaw JS, Wilmot RL, Kilpatrick ES. Establishing pragmatic estimated GFR thresholds to guide metformin prescribing. Diabet Med 2007;24:1160-3. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17672860" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Duong JK, Roberts DM, Furlong TJ, Kumar SS, Greenfield JR, Kirkpatrick CM, et al. Metformin therapy in patients with chronic kidney disease. Diabetes Obes Metab 2012. Doi: 10.1111/j.1463-1326.2012.01617.x. [Epub ahead of print]."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "9.\u{A0}Lipska\u{A0}KJ,\u{A0}Bailey CJ,\u{A0}Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal Insufficiency. Diabetes Care 2011;34:1431-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21617112" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Schumacher S, Abbasi I, Weise D, Hatorp V, Sattler K, Sieber J, et al. Single and multiple dose pharmacokinetics of repaglinide in patients with type 2 diabetes and renal impairment. Eur J Clin Pharmacol 2001;57:147-52. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11417447" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Nagai T, Imamura M, Iizuka K, Mori M. Hypoglycaemia due to nateglinide administration in diabetic patients with chronic renal failure. Diabetes Res Clin Pract 2003;59:191-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12590015" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Chan JC, Scott R, Ferreria JC, Sheng D, Gonzalez E, Davies MJ, et al. Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab 2008;10:545-55. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18518892" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Scott R, Hartley P, Luo E. Use of sitagliptin in patients with type 2 diabetes (T2DM) and renal insufficiency (RI). Diabetes 2006;55 (Suppl 1):A462."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Nowicki M, Rychlik L, Haller H, Warren ML, Suchower L, Gause-Nilsson I, et al. Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab 2011;13:523-32. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21332627" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Lukashevich V, Schweizer A, Shao Q, Groop PH, Kothny W. Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial. Diabetes Obes Metab 2011;13:947-54. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21733061" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Graefe-Mody U, Friedrich C, Port A, Ring A, Retlich S, Heise T, et al. Effect of renal impairment on the pharmacokinetics of the dipeptidylpeptidase-4 inhibidor linagliptin. Diabetes Obes Metab 2011;13:939-46. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21672124" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ito M, Abe M, Okada K, Sasaki H, Maruyama N, Tsuchida M, et al. The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis. Endocr J 2011;58:979-87. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21921362" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Charpentier G, Riveline JP, Varroud-Vial M. Management of drugs affecting blood glucose in diabetic patients with renal failure. Diabetes Metab 2000;26:73-85. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10922977" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Snyder RW, Berns JS. Use of insulin and oral hypoglycemic medications in patients with diabetes mellitus and advanced kidney disease. Semin Dial 2004;17:365-70. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15461745" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Tunbridge FK, Newens A, Home PD, Davis SN, Murphy M, Burrin JM, et al. A comparison of human ultralente- and lente-based twice-daily injection regimens. Diabet Med 1989;6:496-501. <a href="http://www.ncbi.nlm.nih.gov/pubmed/2527130" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "21.\u{A0}Freeman SL, O'Brien PC, Rizza RA. Use of human ultralente as the basal insulin component in treatment of patients with IDDM. Diabetes Res Clin Pract 1991;12:187-92. <a href="http://www.ncbi.nlm.nih.gov/pubmed/1889348" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Selgas R. Comparative study of two different routes for insulin administration in CAPD patients: A multicenter study. Adv Perit Dial 1988;4:126-30."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Coronel F, Naranjo P, Serrano R, Cruceyra A, Prats D. Eficacia de la administración de insulina intraperitoneal en diabéticos sometidos a diálisis peritoneal continua ambulatoria. Med Clin (Barc) 1984;82:881-4."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "24.\u{A0}Fine A, Parry D, Ariano R, Dent W. Marked variation in peritoneal insulin absorption in peritoneal dialysis. Perit Dial Int 2000;20:652-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11216554" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Jacobsen LV, Hindsberger C. Effect of renal impairment on the pharmacokinetics of the GLP-1 analogue liraglutide. Br J Clin Pharmacol 2009;68:898-905. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20002084" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
          ]
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