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Type 2 Diabetes and Chronic Kidney Disease: What Are the Risks? What Are the Tre...
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This article is a CME certified activity. To earn credit for this activity visit: http://www.medscape.org/viewarticle/769116
CME Information
CME Released: 08/21/2012; Valid for credit through 08/21/2013
Target Audience
This educational activity is intended for an international audience of healthcare professionals, excluding US healthcare professionals. This activity is intended for diabetologists, endocrinologists, nephrologists, cardiologists, internists, general practitioners, and primary care physicians, as well as other healthcare professionals who manage diabetes patients with, or at risk for, renal dysfunction.
Goal
The goal of this activity is to improve knowledge of the risks, consequences, and optimal treatment strategies of diabetes patients with renal dysfunction.
Learning Objectives
Upon completion of this activity, participants should be able to: 1. Describe the prevalence, morbidity, and mortality associated with renal dysfunction in people with T2DM 2. Discuss the screening and monitoring of diabetes patients at risk of renal impairment, including the use of appropriate laboratory tests 3. Review the importance of, and drug therapies to achieve, adequate glycemic control to improve renal outcomes in patients with T2DM 4. Compare and contrast pharmacokinetic difference between available DPP-4 inhibitors
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Non-US Physicians - maximum of 0.50 CPD All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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Type 2 Diabetes and Chronic Kidney Disease: What Are the Risks? What Are the Tre... Page 2 of 31
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Moderator
Eleuterio Ferrannini, MD
Professor of Internal Medicine; Chief, Metabolism Unit, National Research Council Institute of Clinical Physiology, University of Pisa School of Medicine, Pisa, Italy Disclosure: Eleuterio Ferrannini, MD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: AstraZeneca Pharmaceuticals LP; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol-
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Myers Squibb Company; Eli Lilly and Company; Merck Sharp & Dohme Corp.; sanofi-aventis Received grants for clinical research from: Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Merck Sharp & Dohme Corp. Dr Ferrannini does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the European Medicines Agency. Dr Ferrannini does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the European Medicines Agency.
Panelists
George L. Bakris, MD
Professor of Medicine; Director, Hypertensive Diseases Unit, University of Chicago Pritzker School of Medicine, Chicago, Illinois Disclosure: George L. Bakris, MD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Abbott Laboratories; CVRx, Inc.; Medtronic, Inc.; Takeda Pharmaceuticals North America, Inc. Served as a speaker or a member of a speakers bureau for: Takeda Pharmaceuticals North America, Inc. Received grants for clinical research from: Forest Laboratories, Inc.; Novartis Pharmaceuticals Corporation Dr Bakris does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the European Medicines Agency. Dr Bakris does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the European Medicines Agency.
Bernard Charbonnel, MD
Professor of Endocrinology and Metabolic Diseases; Head of Internal Medicine, Endocrinology, and Diabetes, University of Nantes, Nantes, France Disclosure: Bernard Charbonnel, MD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: AstraZeneca Pharmaceuticals LP; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol-Myers Squibb Company; Eli Lilly and Company; GlaxoSmithKline; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Roche; sanofi-aventis; Takeda Pharmaceuticals North America, Inc. Served as a speaker or a member of a speakers bureau for: AstraZeneca Pharmaceuticals LP; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol-Myers Squibb Company; Eli Lilly and Company; GlaxoSmithKline; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Roche; sanofi-aventis; Takeda Pharmaceuticals North America, Inc.
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Dr Charbonnel does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the European Medicines Agency. Dr Charbonnel does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the European Medicines Agency.
Mark E. Cooper, MBBS, PhD
Deputy Director and Chief Scientific Officer, Baker IDI Heart & Diabetes Institute, Melbourne, Australia Disclosure: Mark E. Cooper, MBBS, PhD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Boehringer Ingelheim Pharmaceuticals, Inc. Served as a speaker or a member of a speakers bureau for: Merck & Co., Inc.; SERVIER Dr Cooper does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the European Medicines Agency. Dr Cooper does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the European Medicines Agency.
Editor
Anne M. Sendaydiego, PharmD
Scientific Director, WebMD Global, LLC Disclosure: Anne M. Sendaydiego, PharmD, has disclosed no relevant financial relationships.
Steering Committee
Anthony Barnett, MD
Emeritus Professor of Medicine, University of Birmingham; Consultant Physician, Diabetes Centre, Heart of England NHS Foundation Trust, Birmingham, United Kingdom Disclosure: Anthony Barnett, MD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Roche; sanofi-aventis; Takeda Pharmaceuticals North America, Inc. Served as a speaker or a member of a speakers bureau for: Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Roche; sanofi-aventis; Takeda Pharmaceuticals North America, Inc. Received grants for clinical research from: Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Roche; sanofi-aventis; Takeda Pharmaceuticals North America, Inc.
Mark E. Cooper, MBBS, PhD
Deputy Director and Chief Scientific Officer, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia
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Disclosure: As listed above.

Vivian A. Fonseca, MD, FRCP
Professor of Medicine and Pharmacology; Tullis-Tulane Alumni Chair in Diabetes; Chief, Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA Disclosure: Vivian A. Fonseca, MD, FRCP, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Abbott Laboratories; AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Company; Daiichi Sankyo, Inc.; Eli Lilly and Company; GlaxoSmithKline; Novo Nordisk; Pamlab, L.L.C.; sanofi-aventis; Takeda Pharmaceuticals North America, Inc.; XOMA LLC
Per-Henrik Groop, MD, DMSc
Professor of Nephrology, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland Disclosure: Per-Henrik Groop, MD, DMSC, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Abbott Laboratories; Boehringer Ingelheim Pharmaceuticals, Inc.; Cebix Incorporated; Eli Lilly and Company; Novartis Pharmaceuticals Corporation Served as a speaker or a member of a speakers bureau for: Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Genzyme Corporation; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk Received grants for clinical research from: Eli Lilly and Company; Roche
Michael A. Nauck, MD, PhD
Professor of Internal Medicine; Head, Specialist Centre for Diabetes and Metabolic Diseases, Diabetes Centre, Bad Lauterberg, Germany Disclosure: Michael A. Nauck, MD, PhD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Amylin Pharmaceuticals, Inc.; AstraZeneca Pharmaceuticals LP; BerlinChemie AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol-Myers Squibb Company; Diartis Pharmaceuticals; Eli Lilly and Company; F. Hoffmann-La Roche Ltd; GlaxoSmithKline; Intarcia Therapeutics, Inc.; MannKind Corporation; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; sanofi-aventis; Takeda Pharmaceuticals North America, Inc.; Versartis, Inc.; Wyeth Pharmaceuticals Inc.
Andre J. Scheen, MD, PhD
Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, Department of Medicine, Centre Hospitalier Universitaire de Lige, University of Lige, Lige, Belgium Disclosure: Andre J. Scheen, MD, PhD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Company; Eli Lilly and Company; GlaxoSmithKline; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Pfizer Inc.; sanofi-aventis; SERVIER Served as a speaker or a member of a speakers bureau for: AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Company; Eli Lilly and Company; GlaxoSmithKline; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Pfizer Inc.; sanofi-aventis; SERVIER Received grants for clinical research from: Novo Nordisk.
Jiten P. Vora, MD, FRCP
Professor of Medicine; Consultant Physician and Endocrinologist, Royal Liverpool University Hospitals, Liverpool, United Kingdom Disclosure: Jiten P. Vora, MD, FRCP, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Abbott Laboratories; Eli Lilly and Company; Merck Sharp & Dohme
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Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; sanofi-aventis Served as a speaker or a member of a speakers bureau for: Abbott Laboratories; Eli Lilly and Company; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; sanofi-aventis Received grants for clinical research from: Abbott Laboratories; Eli Lilly and Company; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals Corporation; Novo Nordisk; sanofi-aventis
Content Reviewer
Nafeez Zawahir, MD
CME Clinical Director Disclosure: Nafeez Zawahir, MD has disclosed no relevant financial relationships.
Type 2 Diabetes and Chronic Kidney Disease: What Are the Risks? What Are the Treatment Options?CME
Eleuterio Ferrannini, MD; George L. Bakris, MD; Bernard Charbonnel, MD; Mark E. Cooper, MBBS, PhD
CME Released: 08/21/2012; Valid for credit through 08/21/2013
Slide 1.
Eleuterio Ferrannini, MD: Hello, and welcome to Type 2 Diabetes and Chronic Kidney Disease: What Are the Risks? What Are the Treatments Options? I am Eleuterio Ferrannini, Professor of Internal Medicine and Chief of the Metabolism Unit at the National Research Council Institute of Clinical Physiology at the University of Pisa School of Medicine in Pisa, Italy. For this program, I am joined by George L. Bakris, MD, Professor of Medicine and Director of the Hypertensive Diseases Unit at the University of Chicago Pritzker School of Medicine in Chicago, Illinois; Bernard Charbonnel, MD, Professor of Endocrinology and Metabolic Diseases at the University of Nantes, in Nantes, France; and Mark E. Cooper, MBBS, PhD, Deputy Director and Chief Scientific Officer at the Baker IDI Heart & Diabetes Institute in Melbourne, Australia.
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Slide 2.
In this program, we will be discussing the prevalence of renal dysfunction in patients with type 2 diabetes mellitus (T2DM), the morbidity and mortality associated with renal impairment, the appropriate use of a laboratory test to screen and diagnose diabetes patients with renal impairment, the role of glycemic control to prevent or delay a decline in renal function, and novel treatment options to manage hyperglycemia in diabetes patients with or at risk for renal dysfunction. Mark, how significant is the problem of renal dysfunction in patients with T2DM?
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Slide 3.
Mark E. Cooper, MBBS, PhD: People with T2DM often have chronic kidney disease (CKD). As the incidence of T2DM increases, so will the incidence and prevalence of CKD. In patients with end-stage renal disease (ESRD), diabetic nephropathy remains the most common cause. Furthermore, in people with T2DM, CKD is a major risk factor for premature morbidity and mortality; these patients are more likely to have complications including retinopathy, cardiovascular disease (CVD), and lower-limb amputation.
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Slide 4.
The prevalence of CKD in people with T2DM was measured in the Developing Education on Microalbuminuria for Awareness of Renal and Cardiovascular Risk in Diabetes (DEMAND) study. In a sample of over 20,000 T2DM patients from 33 countries, the prevalence of microalbuminuria, a feature of early diabetic renal disease, was almost 40%. 10% of patients had macroalbuminuria, indicating more overt renal disease. Thus, approximately 50% of T2DM patients evaluated in this study had some degree of renal dysfunction. In addition, 22% of patients in the study (with available data), has an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2.
Slide 5.
People with T2DM and comorbid CKD are at a particularly high risk of experiencing adverse cardiovascular (CV) events. In patients with CKD, the prevalence of heart failure and myocardial infarction (MI) is doubled compared to those patients without CKD.
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Type 2 Diabetes and Chronic Kidney Disease: What Are the Risks? What Are the T... Page 10 of 31
Slide 6.
An important clinical problem in people with CKD is that they are at increased risk of experiencing hypoglycemia. In a pooled study of 3 randomized clinical trials, the incidence of investigator-reported hypoglycemia and severe hypoglycemia (ie, hypoglycemia that required assistance) both increased with decreasing eGFR.
Slide 7.
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Dr Ferrannini: I would like to introduce a patient case. John is a 69-year-old white man. He is retired, recently relocated to your city, and is now seeking a new primary care physician. His past medical history includes T2DM for approximately 3 years and dyslipidemia for approximately 10 years. He had a right total knee replacement about 1 year ago. John has a positive family history for T2DM.
Slide 8.
Clinical findings include a body mass index 28.8 kg/m2, blood pressure (BP) of 115/80 mmHg, and a heart rate is 70 beats/minute. Laboratory measurements include a glycosylated hemoglobin (HbA1c) of 7.8%, total cholesterol (TC) of 186 mg/dL, low-density lipoprotein cholesterol (LDL-C) of 100 mg/dL, a high-density lipoprotein-cholesterol (HDL-C) of 45 mg/dL, and triglycerides (TG) of 150 mg/dL. His currents medications include metformin, 1 g twice daily, rosuvastatin 40 mg once daily, and naproxen 500 mg twice daily. This patient has not had diabetes for very long. Is it important to document his renal function at this stage?
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Slide 9.
George L. Bakris, MD: It is very important to document this patient's renal function, as his kidney function is going to be a clear determinant of his CV risk. In a group of over 1 million people within a large, integrated system of healthcare delivery in the US, the association between renal function and risk of death and CV events was measured. In this study, both the risk of death and CV events increased as the eGFR decreased below 60 mL/min/1.73 m2. It is critically important to find out what his eGFR is, because it will give you an estimate of his CV risk.
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Slide 10.
Documenting a patient's kidney function also can give you a better estimate of a patient's prognosis. Kidney Disease: Improving Global Outcomes (KDIGO) initiated a collaborative meta-analysis to examine the relationship of eGFR to mortality and kidney outcomes. On the basis of analyses in 45 cohorts that included 1,555,332 participants from general, high-risk, and kidney disease populations, KDIGO provided a ranking of relative risk according to eGFR. In addition, KDIGO retained the current definition for CKD to be an eGFR <60 mL/min per 1.73 m2 and divided stage 3 into stage 3a and stage 3b, emphasizing clinical diagnosis.
Slide 11.
KDIGO also analyzed the relationship between albuminuria and mortality and kidney outcomes. Higher albuminuria is associated with greater relative risk. Therefore, it is not only necessary to measure a patient's eGFR, but it is also important to document the degree of proteinuria. The more albumin a patient is spilling into the urine, the more likely that a patient will have kidney disease and that the kidney disease will progress. Dr Ferrannini: Is there synergy between decreased eGFR and the presence of albuminuria? Dr Bakris: Yes, there absolutely is. Dr Ferrannini: How would you assess this patient's renal function?
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Slide 12.
Dr Bakris: The International Diabetes Federation (IDF) and the National Institute for Health and Clinical Excellence (NICE) clinical guidelines recommend screening all people with T2DM annually for renal dysfunction staring at diabetes diagnosis. At that time, serum creatinine (SCr) should be measured and the degree of albuminuria should be categorized. GFR can be estimated from the measure SCr using an equation such as the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, which is the latest iteration of the Modification of Diet in Renal Disease equation. The CKD-EPI equation provides a good estimate of GFR, especially over a wide-range of GFRs (ie, between 20 and 70 mL/min/1.73 m2). Blood pressure and glycemic control are important determinants of CKD.
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Slide 13.
It is also important to remember that microalbuminuria by itself, in the absence of any other laboratory/clinical abnormality, does not signify kidney disease. It does, however, signify an increased inflammatory state that could be associated with kidney disease in the future and will need to be monitored over time. Thus, national guidelines recommend to categorize the degree of albuminuria by measuring urinary albumin excretion annually. Dr Ferrannini: Is it important to look for changes over time? Dr Bakris: Yes, absolutely. Dr Ferrannini: How important is adequate glycemic control our patient, or any patient with or at risk for reduced renal function?
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Slide 14.
Bernard Charbonnel, MD: Hyperglycemia is a critical factor for the development of microvascular complications, including nephropathy in people with T2DM. It is why early attainment of tight glycemic control in diabetes patients is critical for reducing the risk of nephropathy and preventing further renal damage.
Slide 15.
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In the United Kingdom Prospective Diabetes Study (UKPDS), which evaluated newly diagnosed T2DM patients, microvascular complications occurred more frequently in patients with higher HbA1c, illustrating the benefit of tight glycemic control in people with T2DM. In fact, for example, every 1% decrease in HbA1c obtained in this study, a 37% reduction in microvascular endpoints, including nephropathy and retinopathy, was observed.
Slide 16.
Similarly, in a population-based cohort study in Canada, which evaluated T2DM patients with established nephropathy (eGFR less than 60 mL/min), improved glycemic control was associated with a lower risk of ESRD.
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Slide 17.
It is important to realize that it takes time for improvements in microalbuminuria to result with glucose control in people with T2DM. In the UKPDS study, significant reductions in microalbuminuria were not noted until after 9 years of good glycemic control, thus, highlighting the importance of providing early and consistent hyperglycemic treatment in T2DM patients with, or at risk for, renal dysfunction.
Slide 18.
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In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, intensive glycemic control was associated with reductions in albuminuria. In over 10,000 patients with T2DM, intensive glycemic treatment (HbA1c less than 6.0%) reduced the risk for microalbuminuria by 15% and the risk for macroalbuminuria by 28% compared with standard glycemic therapy (HbA1c 7.0%-7.9%). Improvements in SCr were not observed in the ACCORD study, possibly due to the relatively short duration of the study.
Slide 19.
Similarly, in the ADVANCE study, patients achieving intensive glucose control (HbA1c less than 6.5%) had reductions in microalbuminuria incidence and macroalbuminuria incidence as well as a reduced risk for renal function worsening and ESRD compared with patients achieving standard glucose control (HbA1c of 7.3%).
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Slide 20.
An HbA1c goal of less than 7% is generally recommended in most people with T2DM. However, as outlined by the recent American Diabetes Association/European Association for the Study of Diabetes Position Statement on the management of hyperglycemia in type 2 diabetes, less stringent goals (eg, 7.5%-8.0%) may be appropriate for patients with a long duration of disease, history of severe hypoglycemia, limited life expectancy, advanced complications, extensive comorbid conditions, and in those in whom the target is difficult to attain. Dr Ferrannini: Our patient does not have hypertension; however, how important is blood pressure (BP) control, in general, in diabetes patients with, or at risk for, reduced renal function?
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Slide 21.
Dr Bakris: BP control is very important. In an analysis of long-term clinical trials in patients with diabetic or nondiabetic kidney disease, lower achieved systolic BP (down to levels around 132-134 mm Hg) was associated with greater preservations of kidney function (ie, eGFR). For many years the recommended BP goal in people with T2DM was less than 130/80 mm Hg. Unfortunately, however, this endpoint has not been achieved in many randomized clinical trials studying patients with diabetic and nondiabetic kidney disease. Systolic BP between 130 and 140 mm Hg has been achieved, which results in a slowing, but not halting of renal disease progression. Under optimal circumstances, the average reduction in eGFR is approximately 3-4 mL/min in people with diabetic nephropathy. Clearly is it important to control BP in order to preserve renal function.
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Slide 22.
The UKPDS demonstrated that reducing BP results in significant beneficial effects in people with T2DM. Tight BP control (144/82 mm Hg) was associated with reductions in diabetes-related death, all-cause mortality, MI, stroke, and microalbuminuria compared with patients that achieved less-tight BP control (154/87 mm Hg). Benefits were observed in people with a systolic BP of 144 mm Hg, which is above the recommended goal BP of less than 130 mm Hg.
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Slide 23.
Dr Ferrannini: Let us now return to our patient, John. His SCr was 1.5 mg/dL, which translates to an eGFR of 46 mL/min/1.73 m2. His albumin:creatinine ratio is 60 mg/g creatinine. What considerations would you make in selecting an antihyperglycemic regimen in this or another diabetes patient with some degree of kidney disease?
Slide 24.
Dr Charbonnel: The first topic that I would like to discuss is the use of metformin in diabetes patients with CKD. Metformin is the usual first-line agent to use when lifestyle modifications have failed to control hyperglycemia. However, metformin is eliminated via the kidneys and some (rare) cases of lactic acidosis have been reported with in diabetes patients with CKD. Metformin is a safe hypoglycemic agent to use in T2DM patients with CKD. Alternative antihyperglycemic agents are associated with greater safety concerns. Sulfonylureas and insulin are associated with severe hypoglycemia and thiazolidinediones are associated with fluid retention.
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Slide 25.
A critical review of the literature supports the safe use of appropriate doses of metformin in diabetes patients with renal impairment. Metformin can be used safely in diabetes patients with eGFR of 30-60 mL/min. Dose reduction should be considered in patients with eGFR lower than 45 mL/min. Metformin should not be used in patients with eGFR higher than 30 mL/min.
Slide 26.
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Other traditional antihyperglycemic agents, including sulfonylureas, glinides, thiazolidinediones, and insulin are available to treat hyperglycemia in patients with T2DM. Sulfonylureas are primarily eliminated via the kidneys. Sulfonylureas are also associated with a high risk of hypoglycemia. Therefore, since the risk of hypoglycemia is increased in patients with CKD, the risk of hypoglycemia will be even higher in those diabetes patients taking a sulfonylurea with concomitant renal impairment. Patients should be monitored closely for signs and symptoms of hypoglycemia. First-generation sulfonylureas should be avoided in diabetes patients with renal impairment. With respect to the second-generations sulfonylureas, shorter-acting agents are preferred compared with longer-acting agents. Glinides are primarily eliminated via the cytochrome P450 system and therefore can be used in CKD patients without dose adjustments. When using a thiazolidinedione such as pioglitazone, the dose does not need to be adjusted in patients with renal impairment. Fluid retention, however, is common with these agents and, therefore, fluid status must be carefully monitored in these patients. Insulin is often used in diabetes patients with CKD, however, insulin is degraded by the kidneys, which may result in a higher risk of hypoglycemia. Insulin doses must be carefully titrated to avoid excess hypoglycemia in diabetes patients with renal impairment.
Slide 27.
When using many different antihyperglycemic agents, adjustment in the dose for renal function is required. A clear unmet need exists for safe and efficacious antihyperglycemic therapies, ideally without the need for dose adjustments that can be used in diabetes patients with CKD.
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Slide 28.
In patients with T2DM, incretin-based agents provide clinically important reductions in HbA1c with a low risk for hypoglycemia and neutral or beneficial effects on body weight. While, several clinical and practical differences exist between dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, either class may be considered for hyperglycemia treatment in diabetes patients with CKD. Dr Ferrannini: The potential role of DPP-4 inhibitors in the treatment of diabetes patients with renal dysfunction has been mentioned. What are some of the differences between the available DPP-4 inhibitors?
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Slide 29.
Dr Cooper: DPP-4 inhibitors are effective in reducing HbA1c levels. However, as most are renally excreted, caution is needed when selecting them for treatments in patients with CKD, as dose adjustment may be needed.
Slide 30.
The importance of this is as can be seen in this slide, is that linagliptin, for example, has only less than 5% renal excretion, whereas the other gliptins are at least 50 and up to almost 90% cleared by the kidneys; therefore, if
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you have a person with renal impairment, you have a potential for accumulation of some of these DPP-4 inhibitors and therefore dose adjustment or contraindication is sometimes needing to be considered. Fortunately, we have one DPP-4 inhibitor, linagliptin, which does not need the dose altered with people with low GFR, and so this is clearly an appropriate drug to consider with chronic kidney disease.
Slide 31.
Linagliptin has been shown to effectively reduce HbA1c in diabetes patients with no, mild, or moderate renal impairment. A similar reduction in HbA1c (approximately 0.6%) is observed in all three patient populations, which is consistent with the glucose reductions observed with other DPP-4 inhibitors.
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Slide 32.
Dr Ferrannini: In summary, impairment of renal function is much more common in people with T2DM than previously considered, especially as the diabetes population ages. Even in patients with a short duration of diabetes disease, there is a need to assess renal function. Serum creatinine, eGFR, and degree of proteinuria should be monitored regularly over the duration of patients' T2DM. Adequate control of BP is important to preserve renal function in people with T2DM. While a BP of less than 130/80 mm Hg is currently recommended in T2DM patient, this level of control is often difficult to achieve. In general, therefore, the lowest level of BP that does not induce side effects or complications should be the goal.
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Slide 33.
It is equally critical to achieve adequate glycemic control to preserve renal function in people with T2DM. An HbA1c of less than 7.0% is recommended for most patients, however, this goal should be individualized according to patient needs and factors. Several different classes of antihyperglycemic agents are available to treat people with T2DM. It is important to select agents that effectively reduce blood glucose without exposing the patient to unnecessary safety risks. Traditional antihyperglycemic agents are often associated with clinical challenges, including hypoglycemia with sulfonylureas, fluid retention with thiazolidinediones, as well as the need for dosage adjustments in patients with renal dysfunction. DPP-4 inhibitors are new, incretin-based therapies available to treat hyperglycemia in people with T2DM. Generally speaking, DPP-4 inhibitors are very well-tolerated and efficacious drugs; however, pharmacokinetic differences exist between the available agents. Sitagliptin, saxagliptin, and vildagliptin are primarily eliminated via the kidneys. These agents are either not recommended in patients with renal dysfunction or their doses must be adjusted based on the degree of renal dysfunction in the patient. Linagliptin is primarily eliminated by hepatic/nonrenal routes of elimination, therefore dose adjustments are not required in patients with mild, moderate, or severe CKD.
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Slide 34.
Thank you for viewing this program. We hope that you found it interesting and that the information will help you manage your diabetes patients who have, or are at risk for, CKD. This transcript has been edited for style and clarity.
Disclaimer The information contained in this activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options for a specific patient's medical condition. The viewpoints expressed in this activity are those of the authors/faculty and do not necessarily reflect the views of WebMD Global LLC, its affiliated companies or any company that supports educational programming on www.medscape.org. You should exercise your professional judgment in evaluating these materials and consult other relevant sources before undertaking any treatment based on these materials. Please consult your local prescribing information prior to making any treatment decisions based on information contained in this educational activity. Medscape Education 2012 WebMD Global, LLC
12.09.2012

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Type 2 Diabetes and Chronic Kidney Disease: What Are the Risks? What Are the Tre...

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