The Effects of Glucose-Lowering Therapies on Diabetic Kidney Disease (original) (raw)
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Therapeutic Advances in Endocrinology and Metabolism, 2021
Type 2 diabetes is a leading cause of chronic kidney disease worldwide and continues to increase in prevalence. This in turn has significant implications for healthcare provision and the economy. In recent years there have been multiple advances in the glucose-lowering agents available for the treatment of diabetes, which not only modify the disease itself but also have important benefits in terms of the associated cardiovascular outcomes. The cardiovascular outcome trials of agents such as glucagon-like peptide-1 receptor agonists (GLP-RAs) and sodium glucose cotransporter 2 inhibitors (SGLT-2) have demonstrated significant benefits in reducing major adverse cardiovascular events, admissions for heart failure and in some cases mortality. Secondary analysis of these trials has also indicated significant renoprotective benefit. Canagliflozin and Renal Outcomes in Type 2 Diabetes Mellitus and Nephropathy (CREDENCE) a renal-specific trial, has shown major benefits with canagliflozin for renal outcomes in diabetic kidney disease, and similar trials with other SGLT-2 inhibitors are either underway or awaiting analysis. In this article we review current goals of treatment of diabetes and the implications of advancing renal impairment on choice of treatments. Areas discussed include the diagnosis of diabetic kidney disease and current treatment strategies for diabetic kidney disease ranging from lifestyle modifications to glycaemic control. This review focuses on the role of GLP-RAs and SGLT-2 inhibitors in treating those with diabetes and chronic kidney disease with some illustrative cases. It is clear that these agents should now be considered first choice in combination with metformin in those with diabetes and increased cardiovascular risk and/or reduced renal function, and in preference to other classes such as dipeptidyl peptidase-4 (DPP-4) inhibitors or sulphonylureas.
Achieving glycemic control in patients with type 2 diabetes and renal impairment
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Choice of Antihyperglycemic Agents in Patients with Chronic Kidney Disease
Interventions in Obesity & Diabetes, 2018
Chronic kidney disease (CKD) is one of the most frequent microvascular complications of diabetes. Approximately 40% of adults with type 2 diabetes mellitus (T2DM) have CKD and about 50% of end-stage renal disease (ESRD) is caused by diabetes [1,2]. The hypoglycemia risk is increased in patients with advanced CKD (CKD stages 4 & 5) since clearance of insulin and of some of the non-insulin antihyperglycemic agents is reduced and there is an impaired renal gluconeogenesis with reduced kidney mass [3,4]. The number of non-insulin antihyperglycemic agents that can be used safely to manage diabetes in patients with CKD is therefore, limited and insulin dose usually requires an adjustment to avoid hypoglycemia. It is important that the choice of antihyperglycemic agents is reviewed regularly as CKD stage advances and the doses are readjusted based on CKD stage to avoid hypoglycemia (Table 1).
A narrative review of new treatment options for chronic kidney disease in type 2 diabetes
Annals of Translational Medicine, 2021
Diabetic kidney disease is a frequent and costly complication to type 2 diabetes. After many years with a lack of successful trials there are now significant developments that will change treatment, guidelines and future outcome. Since the last two decades blockade of the renin-angiotensin system (RAS) is standard treatment, but new antidiabetic treatments have shown potential for kidney protection. After cardiovascular outcome studies with glucagon-like peptide (GLP-1) receptor agonists it is evident that drugs like liraglutide, semaglutide and dulaglutide can reduce albuminuria levels and progression to macroalbuminuria. At present, a renal outcome trial with semaglutide is ongoing which will provide more evidence on the drug class in the future. The sodium glucose co-transporter 2 (SGLT2) inhibitor class has also demonstrated effects beyond glucose-lowering, as the drugs can reduce blood pressure, albuminuria and loss of renal function. In the first renal outcome study the SGLT2 inhibitor canagliflozin was found to reduce the risk of hard renal outcome with 30%. SGLT2 inhibition is now recommended in type 2 diabetes with chronic kidney disease. Renal outcome studies testing additional SGLT2 inhibitors and the GLP-1 receptor agonist semaglutide will report in the coming future potentially providing more and much needed options for treatment.
Antidiabetic Medication in Patients with Chronic Kidney Disease: What's New?
Nephrology @ Point of Care
Diabetic nephropathy is one of the most frequent microvascular complications in diabetic patients. This report describes a case of diabetic nephropathy in an male adult (diabetic) patient treated with standard therapy and the contribution of the new antidiabetic drugs on the progression of the disease. We will deal the following questions: 1. What do we know about diabetic nephropathy and its natural history? 2. How should we manage diabetic nephropathy and what do the guidelines suggest on hyperglycemia? 3. How do we manage hyperglycemia in diabetic patients with chronic kidney disease (CKD)? Standard treatment. 4. What's news about antidiabetic medication? New treatment. 5. What's next?
Indian Journal of Public Health Research & Development, 2019
Background: Diabetic Nephropathy plays a key role in the function of kidneys to work for removing extra fluid and waste products from the body. The best way to prevent diabetic nephropathy is by maintaining a healthy lifestyle and treating diabetes and high blood pressure. Aim of the study was to locate the levels of Glucagon-Like Peptide-1 and Dipeptidyl Peptidase-4 in diabetic nephropathy patients and compare the results with the control group. Methods: The study involved 30 healthy controls and 30 diabetic nephropathy patients. Blood samples were collected from healthy controls and diabetic nephropathy patients after 12-14 hours of fasting. The study was conducted between April 2015 and September 2015 in the diabetic & endocrinology center in Al-Sadder Medical City, Iraq. Whole blood used in determination of HbA1 C. Serum was obtained from other part of blood that used in determination of FBG, Albumin, Urea, Creatinine, Total cholesterol, Triglyceride, high-density lipoprotein-cholesterol, GLP-1 and DPP-4. The levels of low-density lipoprotein-cholesterol and very low-density lipoprotein-cholesterol were analyzed by using Friedewald equation.. Results: The results showed significant elevation in FBG, HbA1 C , GLP-1 and DPP-4 levels in diabetic nephropathy group comparing to control group. There was illustrated significant increased in TC, TG, LDL-c and VLDL-c in diabetic nephropathy group comparing to control group, while a significant decrease was noticed in HDL-c level in the patient group compared with the control group. Also, results of current study revealed a significant decrease in Albumin levels in diabetic nephropathy group comparing to control group. Moreover, the study showed a significant increase in Creatinine, Urea and Blood Pressure Levels in diabetic nephropathy group comparing to control group. Conclusion: there is significant association between Diabetic Nephropathy and raised FBS, HbA1C, GLP-1, DPP-4, TC, TG, LDL-c, VLDL-c, Creatinine, Urea levels and Blood Pressure and significant decrease in Albumin, HDL-c level in diabetic nephropathy group compared to control group. It is, therefore, recommended to use (DPP-4) inhibitors which stimulate insulin release and inhibit glucagon releaseng.
Management of hyperglycemia in patients with chronic kidney disease
Journal of Nephrology, 2013
Diabetes currently accounts for approximately 45% of cases of end-stage renal failure in patients undergoing hemodialysis. Several observational studies have identified a positive correlation between measures of glycemic control and cardiovascular and microvascular benefits. Several randomized prospective studies have been conducted to quantify the impact of strict glycemic control on morbidity and mortality. These studies have consistently demonstrated an association between strict glycemic control and a reduction in microvascular events, but these results contrast with the lack of consistent results regarding macrovascular events. Treating diabetes has always been challenging. This challenge is increased in chronic kidney disease, due to changes in the pharmacokinetics and pharmacodynamics of insulin and most oral antidiabetic agents. The available pharmacotherapeutic arsenal for treating type 2 diabetes mellitus currently involves approximately 6 different pharmacological classes of oral antidiabetic agents and different modalities of insulin therapy.
Glycemic Excursions in Diabetic Kidney Disease: Comparison of Three Therapeutic Arms
Endocrinology&Metabolism International Journal, 2018
Objectives/Aim of study: To assess the magnitude of glycemic variability (based on blood glucose levels) over 72hours in patients with underlying diabetic kidney disease and HbA1c <8%, and to compare the effects of glimepiride, vildagliptin and insulin on glycemic variability. Materials and Methods: Thirty patients of T2 DM and diabetic kidney disease were chosen whose HbA1C was less than 8%, fasting plasma glucose less than 150mg/dL, two hour post prandial plasma glucose less than 200mg/ dl, eGFR-between 15 to 59ml/min/1.73m 2. Exclusion criteria were pregnancy, pre-existing non diabetic kidney disease, decompensated heart failure, liver failure and systemic infections. Patients were categorized into three groups:on glimepiride (n=10),on vildagliptin (n=10) and on basal bolus insulin (n=10). Medications were adjusted to patients' renal function. Patients were managed for their diabetes following the most recent ADA guidelines. Patients underwent CGM for 72hours and the results were analyzed. Results: Post dinner capillary blood glucose (CBG) was found to be significantly higher in the glimepiride (228 mg/dl ±37.66) cohort than Endocrinology & Metabolism International Journal Research Article Open Access vildagliptin (196mg/dl ±40.43) cohort (p=0.043) and the predinner CBG was significantly higher in the insulin (130mg/dl ±45.08) cohort than vildagliptin (92.89mg/dl ±26.06) cohort (p=0.047). No significant difference in daytime as well as nocturnal hypoglycemia was noted among the three arms. Conclusion: CGMS can reveal episodes of glycemic instability in a diabetic patient categorized as having stable glycemia by HbA1c, FPG and PPPG. Insulin, Glimepiride and Vildagliptin did not differ markedly in reducing glycemic variability in our study. Strict implementation of lifestyle modification and glycemic control can influence the extent of glycemic variability, which may have influenced the results. Small sample size was also a limiting factor in our study. However, rational and judicious use of antidiabetic medications may help in reducing glycemic variability and hypoglycemic episodes, even in diabetic kidney disease.