incretins and Renal-Insufficiency--Chronic

Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide. Development of DKD increases risks for cardiovascular events and death. Glucagon-like peptide-1 (GLP-1) receptor agonist have demonstrated improved cardiovascular and kidney outcomes in large-scale clinical trials.. GLP-1 and dual GLP-1/glucose-depending insulinotropic polypeptide (GIP) receptor agonists have robust glucose-lowering efficacy with low risk of hypoglycemia even in advanced stages of DKD. Initially approved as antihyperglycemic therapies, these agents also reduce blood pressure and body weight. Cardiovascular outcome and glycemic lowering trials have reported decreased risks of development and progression of DKD and atherosclerotic cardiovascular events for GLP-1 receptor agonists. Kidney and cardiovascular protection is mediated partly, but not entirely, by lowering of glycemia, body weight, and blood pressure. Experimental data have identified modulation of the innate immune response as a biologically plausible mechanism underpinning kidney and cardiovascular effects.. An influx of incretin-based therapies has changed the landscape of DKD treatment. GLP-1 receptor agonist use is endorsed by all major guideline forming organizations. Ongoing clinical trials and mechanistic studies with GLP-1 and dual GLP-1/GIP receptor agonists will further define the roles and pathways for these agents in the treatment of DKD.

Topics: Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Incretins; Renal Insufficiency, Chronic

The prevalence of obesity in the United States and across the world continues to climb, imparting increased risk of chronic disease. This impact is doubly felt in nephrology because obesity not only increases the risk of chronic kidney disease (CKD) but also exacerbates existing cardiovascular morbidity and mortality. The role of medical weight loss therapy in CKD has been debated, but increasing evidence suggests that intentional weight loss is protective against adverse kidney and cardiovascular outcomes. This may be particularly true with the advent of novel pharmacotherapies taking advantage of the incretin system, resulting in weight loss approaching that seen with surgical interventions. Moreover, these novel therapies have repeatedly demonstrated protective effects on the cardiovascular system. Here, we review the impact of obesity and weight loss on CKD, and the biological basis and clinical evidence for incretin therapy. This perspective provides recommended prescribing practices as a practical tool to engage nephrologists and patients with CKD in the treatment of obesity-related morbidity.

Topics: Humans; Incretins; Nephrologists; Obesity; Renal Insufficiency, Chronic; United States; Weight Loss

Diabetic kidney disease (DKD) is one of the most important diabetic complications. DKD is also the most common cause of chronic kidney disease (CKD) and end-stage renal disease. This review focused on potential therapeutic drugs for which there is established evidence of treatment for DKD. The earliest evidence for DKD treatment was established with renin-angiotensin system (RAS) inhibitors; however, their efficacy was partial. Recently, the sodium-glucose co-transporter 2 (SGLT2) inhibitors, including empagliflozin (EMPA-REG Outcome), canagliflozin (CREDENCE trial), and dapagliflozin (DAPA-CKD), demonstrated a significant and clinically relevant reduction in the risks of albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy. Additionally, incretin-based therapeutic agents, such as glucagon-like peptide 1, liraglutide (LEADER), and dipeptidyl peptidase 4 inhibitors, linagliptin (CARMERINA) have elicited vasotropic actions, suggesting a potential for reducing the risk of DKD. Until recently, mineralocorticoid receptor antagonists (MRAs) have not been suitable for DKD treatment because of their adverse effect of hyperkalemia. In contrast, finerenone, a non-steroidal MRA, significantly reduced renal composite endpoint without severe hyperkalemia that would force its discontinuation (FIDELIO-DKD). Thus, the mainstay treatments of DKD are RAS inhibitors, SGLT2 inhibitors, incretin-based therapeutic agents, and non-steroidal MRA, or in other words, the DKD "fantastic four".

Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hyperkalemia; Incretins; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors

Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.. We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized.. Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75-0.96] and 0.68 [0.59-0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80-1.04] and 0.86 [0.72-1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78-1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63-0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69-0.95]), while exendin-4 analogues did not (RR 1.03 [0.88-1.20]).. In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Disease Progression; Female; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; Male; Network Meta-Analysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Endothelin A Receptor Antagonists; Humans; Incretins; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors

Type 2 diabetes is the leading cause of chronic kidney disease (CKD). The prevalence of CKD is growing in parallel with the rising number of patients with type 2 diabetes globally. At present, the optimal approach to glycaemic control in patients with type 2 diabetes and advanced CKD (categories 4 and 5) remains uncertain, as these patients were largely excluded from clinical trials of glucose-lowering therapies. Nonetheless, clinical trial data are available for the use of incretin therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, for patients with type 2 diabetes and advanced CKD. This review discusses the role of incretin therapies in the management of these patients. Because the presence of advanced CKD in patients with type 2 diabetes is associated with a markedly elevated risk of cardiovascular disease (CVD), treatment strategies must include the reduction of both CKD and CVD risks because death, particularly from cardiovascular causes, is more probable than progression to end-stage kidney disease. The management of hyperglycaemia is essential for good diabetes care even in advanced CKD. Current evidence supports an individualized approach to glycaemic management in patients with type 2 diabetes and advanced CKD, taking account of the needs of each patient, including the presence of co-morbidities and concomitant therapies. Although additional studies are needed to establish optimal strategies for glycaemic control in patients with type 2 diabetes and advanced CKD, treatment regimens with currently available pharmacotherapy can be individually tailored to meet the needs of this growing patient population.

Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Humans; Hyperglycemia; Hypoglycemic Agents; Incretins; Renal Insufficiency, Chronic

Type 2 diabetes is the leading cause of impaired kidney function, albuminuria, and renal replacement therapy globally, thus placing a large burden on health-care systems. Current treatment strategies rely on intensive glucose lowering as well as strict blood pressure control through blockade of the renin-angiotensin-aldosterone system. Such approaches might slow decline in kidney function, but many patients progress to end-stage kidney failure despite optimal therapy. In recent clinical trials, new-generation glucose-lowering drug classes, the sodium-glucose co-transporter-2 inhibitors and agents that target the incretin pathway, have been shown to improve kidney outcomes in patients with type 2 diabetes. Other new approaches, which have been developed on the basis of an improved understanding of the mechanisms that contribute to kidney damage in the context of diabetes, include use of drugs that block endothelin receptors (eg, atrasentan) and non-steroidal mineralocorticoid receptors (eg, finerenone). In this Review, we provide an overview of recent clinical data relevant to these new therapeutic approaches for management of kidney disease in the context of type 2 diabetes.

Topics: Antihypertensive Agents; Atrasentan; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Endothelin Receptor Antagonists; Humans; Hypoglycemic Agents; Incretins; Mineralocorticoid Receptor Antagonists; Naphthyridines; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors

Type 2 diabetes mellitus (T2DM) is the most common cause of chronic kidney disease (CKD), and when it causes CKD it is collectively referred to as diabetic kidney disease. One of the newer therapies for managing hyperglycemia is the glucagon-like peptide-1 receptor agonist (GLP-1RA) drug class. This review summarizes the effects of GLP-1RAs in patients with T2DM with CKD and evidence for renoprotection with GLP-1RAs using data from observational studies, prospective clinical trials, post hoc analyses, and meta-analyses. Evidence from some preclinical studies was also reviewed. Taken together, subgroup analyses of patients with varying degrees of renal function demonstrated that glycemic control with GLP-1RAs was not markedly less effective in patients with mild or moderate renal impairment vs that in patients with normal function. GLP-1RAs were associated with improvements in some cardiorenal risk factors, including systolic blood pressure and body weight. Furthermore, several large cardiovascular outcome studies showed reduced risks of composite renal outcomes, mostly driven by a reduction in macroalbuminuria, suggesting potential renoprotective effects of GLP-1RAs. In conclusion, GLP-1RAs effectively reduced hyperglycemia in patients with mild or moderately impaired kidney function in the limited number of studies to date. GLP-1RAs may be considered in combination with other glucose-lowering medications because of their ability to lower glucose in a glucose-dependent manner, lowering their risk for hypoglycemia, while improving some cardiorenal risk factors. Potential renoprotective effects of GLP-1RAs, and their renal mechanisms of action, warrant further investigation.. 2型糖尿病(type 2 diabetes mellitus, T2DM)是慢性肾脏病(chronic kidney disease, CKD)最常见的病因, 当引起CKD时统称为糖尿病肾病。胰高血糖素样肽-1受体激动剂(glucagon-like peptide-1 receptor agonist, GLP-1RA)是一类较新的降糖药物。本综述利用来自观察性研究、前瞻性临床试验、事后分析以及meta分析的数据, 总结了GLP-1RAs在T2DM合并CKD患者中的疗效及GLP-1RAs肾脏保护的证据。同时还回顾了一些来自临床前研究的证据。分析显示, 不同程度肾功能患者的亚组分析表明, 与肾功能正常的患者相比较, 轻度或中度肾功能受损患者使用GLP-1Ras治疗的降糖疗效并未明显降低。GLP-1RAs可改善一些心肾危险因素, 包括收缩压与体重。此外, 几项大型心血管结局研究结果显示, 复合肾脏结局的风险降低, 这主要是由于大量白蛋白尿减少所致, 表明GLP-1RAs具有潜在的肾脏保护作用。总之, 迄今为止有限的几项研究显示GLP-1RAs可有效降低轻度或中度肾功能受损患者的血糖水平。目前认为GLP-1RAs可与其他降糖药物联合使用, 因其降糖作用呈葡萄糖依赖性, 可降低发生低血糖的风险, 同时还可改善一些心肾危险因素。GLP-1RAs的潜在肾脏保护作用及其作用机制值得进一步研究。.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Kidney; Renal Insufficiency, Chronic; Signal Transduction; Treatment Outcome

The pharmacokinetics and pharmacodynamics of antidiabetic therapies for patients with type 2 diabetes are often altered in the context of chronic kidney disease (CKD).. Systematic review and meta-analysis.. Patients with type 2 diabetes and CKD.. 2 reviewers independently screened studies identified through bibliographic databases (Cochrane Library, PubMed, Embase, International Pharmaceutical Abstracts), clinical trial registries, and references from pertinent articles and clinical practice guidelines. Eligible studies included randomized controlled trials evaluating incretin-based therapy in adults with type 2 diabetes and estimated glomerular filtration rates < 60mL/min/1.73m. Incretin-based therapies (dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists) compared to placebo or active antidiabetic therapies.. Changes in glycated hemoglobin (HbA. Of 1,619 nonduplicate records screened, 13 studies were included. Compared to placebo, incretin-based therapies significantly reduced HbA. Variation among interventions, small number of studies, heterogeneity between studies, and high risk for attrition bias in 7 of the selected studies.. In patients with moderate or severe CKD, incretin-based therapies are effective in reducing HbA

Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Incretins; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Treatment Outcome

The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic agents have limitations in patients with CKD, incretin-based therapies are increasingly used for the management of T2DM. This review analyses (1) the influence of CKD on the pharmacokinetics of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists; and (2) the efficacy/safety profile of these agents in clinical practice when prescribed in patients with both T2DM and CKD. Most DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin) are predominantly excreted by the kidneys. Thereby, pharmacokinetic studies showed that total exposure to the drug is increased in proportion to the decline of GFR, leading to recommendations for appropriate dose reductions according to the severity of CKD. In these conditions, clinical studies reported a good efficacy and safety profile in patients with CKD. In contrast, linagliptin is eliminated by a predominantly hepatobiliary route. As a pharmacokinetic study showed only minimal influence of decreased GFR on total exposure, no dose adjustment of linagliptin is required in the case of CKD. The experience with GLP-1 receptor agonists in patients with CKD is more limited. Exenatide is eliminated by renal mechanisms and should not be given in patients with severe CKD. Liraglutide is not eliminated by the kidney, but it should be used with caution because of the limited experience in patients with CKD. Only limited pharmacokinetic data are also available for lixisenatide, exenatide long-acting release (LAR) and other once-weekly GLP-1 receptor agonists in current development. Several case reports of acute renal failure have been described with GLP-1 receptor agonists, probably triggered by dehydration resulting from gastrointestinal adverse events. However, increasing GLP-1 may also exert favourable renal effects that could contribute to reducing the risk of diabetic nephropathy. In conclusion, the already large reassuring experience with DPP-4 inhibitors in patients with CKD offers new opportunities to the clinician, whereas more caution is required with GLP-1 receptor agonists because of the limited experience in this population.

Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Receptors, Glucagon; Renal Insufficiency, Chronic

Chronic hyperglycemia and its associated metabolic products are key factors responsible for the development and progression of diabetic chronic kidney disease (CKD). Endocrinologists are tasked with detection and management of early CKD before patients need referral to a nephrologist for advanced CKD or dialysis evaluation. Primary care physicians are increasingly becoming aware of the importance of managing hyperglycemia to prevent or delay progression of CKD. Glycemic control is an integral part of preventing or slowing the advancement of CKD in patients with diabetes; however, not all glucose-lowering agents are suitable for this patient population. The availability of the latest information on treatment options may enable physicians to thwart advancement of serious renal complication in patients suffering from diabetes. This review presents clinical data that shed light on the risk/benefit profiles of three relatively new antidiabetes drug classes, the dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 analogs, and sodium glucose co-transporter 2 inhibitors, particularly for patients with diabetic CKD, and summarizes the effects of these therapies on renal outcomes and glycemic control for endocrinologists and primary care physicians. Current recommendations for screening and diagnosis of CKD in patients with diabetes are also discussed.

Topics: Antihypertensive Agents; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Disease Progression; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors

Incretin-based drugs, i.e., glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are widely used for the treatment of type 2 diabetes. In addition to the primary role of incretins in stimulating insulin secretion from pancreatic β-cells, they have extra pancreatic functions beyond glycemic control. Indeed, recent studies highlight the potential beneficial effects of incretin-based therapy in diabetic kidney disease (DKD). Experimental studies using various diabetic models suggest that incretins protect the vascular endothelium from injury by binding to GLP-1 receptors, thereby ameliorating oxidative stress and the local inflammatory response, which reduces albuminuria and inhibits glomerular sclerosis. In addition, there is some evidence that GLP-1 receptor agonists and DPP-4 inhibitors mediate sodium excretion and diuresis to lower blood pressure. The pleiotropic actions of DPP-4 inhibitors are ascribed primarily to their effects on GLP-1 signaling, but other substrates of DPP-4, such as brain natriuretic peptide and stromal-derived factor-1α, may have roles. In this review, we summarize recent studies of the roles of incretin-based therapy in ameliorating DKD and its complications.

Topics: Acute Kidney Injury; Animals; Blood Pressure; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; Receptors, Glucagon; Renal Insufficiency, Chronic; Signal Transduction

Type 2 diabetes mellitus (T2DM) with concomitant CKD is an emerging clinical and public health problem reaching epidemic proportions in the United States. Achieving and maintaining glycemic targets in clinical practice are significant challenges in majority of the patients with T2DM and CKD, and this has created significant barriers for clinicians managing these patients. Commonly used antihyperglycemic agents are either contraindicated or lack efficacy and safety information in this population. Recently, 2 distinct classes of agents that augment incretin hormone action have been added to the therapeutic armamentarium targeting hyperglycemia. This review will discuss the literature examining the efficacy and safety of incretin-based therapies in T2DM and the available evidence for their use in CKD.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hypoglycemic Agents; Incretins; Renal Insufficiency, Chronic; Treatment Outcome

An elevated level of urinary albumin to creatinine ratio (UACR) is a marker of renal dysfunction and predictor of kidney failure/death in patients with type 2 diabetes. The prognostic use of UACR in established cardiac biomarkers is not well described.. To evaluate whether UACR offers incremental prognostic benefit beyond risk factors and established plasma cardiovascular biomarkers.. The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 study was performed from May 2010 to May 2013 and evaluated the safety of saxagliptin vs placebo in patients with type 2 diabetes with overt cardiovascular disease or multiple risk factors. Median follow-up was 2.1 years (interquartile range, 1.8-2.3 years).. Patients were randomized to saxagliptin vs placebo plus standard care.. Baseline UACR was measured in 15 760 patients (95.6% of the trial population) and categorized into thresholds.. Of 15 760 patients, 5205 were female (33.0%). The distribution of UARC categories were: 5805 patients (36.8%) less than 10 mg/g, 3891 patients (24.7%) at 10 to 30 mg/g, 4426 patients (28.1%) at 30 to 300 mg/g, and 1638 patients (10.4%) at more than 300 mg/g. When evaluated without cardiac biomarkers, there was a stepwise increase with each higher UACR category in the incidence of the primary composite end point (cardiovascular death, myocardial infarction, or ischemic stroke) (3.9%, 6.9%, 9.2%, and 14.3%); cardiovascular death (1.4%, 2.6%, 4.1%, and 6.9%); and hospitalization for heart failure (1.5%, 2.5%, 4.0%, and 8.3%) (adjusted P < .001 for trend). The net reclassification improvement at the event rate for each end point was 0.081 (95% CI, 0.025 to 0.161), 0.129 (95% CI, 0.029 to 0.202), and 0.056 (95% CI, -0.005 to 0.141), respectively. The stepwise increased cardiovascular risk associated with a UACR of more than 10 mg/g was also present within each chronic kidney disease category. The UACR was associated with outcomes after including cardiac biomarkers. However, the improvement in discrimination and reclassification was attenuated; net reclassification improvement at the event rate was 0.022 (95% CI, -0.022 to 0.067), -0.008 (-0.034 to 0.053), and 0.043 (-0.030 to 0.052) for the primary end point, cardiovascular death, and hospitalization for heart failure, respectively.. In patients with type 2 diabetes, UACR was independently associated with increased risk for a spectrum of adverse cardiovascular outcomes. However, the incremental cardiovascular prognostic value of UACR was minimal when evaluated together with contemporary cardiac biomarkers.. clinicaltrials.gov Identifier: NCT01107886.

Topics: Adamantane; Albuminuria; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diabetic Nephropathies; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Incretins; Male; Renal Insufficiency, Chronic

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Incretins; Obesity; Renal Insufficiency, Chronic

Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI.. We collected data from 46 diabetes clinics (n = 281,381 T2D patients), extracted data to calculate HSI and validated it against ultrasound-detected hepatic steatosis. We then examined changes in HSI among patients with a follow-up visit within 1 year after initiating newer GLMs.. MAFLD (defined by HSI > 36, i.e., a high probability of steatosis) was present in 76.3% of the 78,895 included patients, while only 2.7% had HSI < 30 (low probability of steatosis). After age- and sex-adjusting, higher HSI was associated with higher prevalence of chronic kidney disease (odds ratio 1.35; 95%CI 1.22-1.51) and macroangiopathy (odds ratio 1.18; 95%CI 1.07-1.30). Among 2,179 subjects in the validation cohort, the prevalence of MAFLD was 67.8% and was greater in those with high HSI. Performance of HSI for ultrasound-detected MAFLD was moderate (AUROC 0.70), yet steatosis prevalence was > threefold higher among subjects with HSI > 36 than among those with HSI < 30. Notably, HSI declined significantly ~ 6 months after initiation of dapagliflozin or incretin-based therapies, but not gliclazide.. About three quarters of patients with T2D have HSI values suggestive of MAFLD, a condition associated with macroangiopathy and nephropathy. Treatment with dapagliflozin or incretin therapies might improve MAFLD in T2D.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Fatty Liver; Female; Follow-Up Studies; Gliclazide; Humans; Hypoglycemic Agents; Incretins; Italy; Male; Middle Aged; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome; Ultrasonography; Young Adult

Topics: Adult; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Kidney; Renal Insufficiency, Chronic; Treatment Outcome

Topics: Adamantane; Albuminuria; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Glucosides; Humans; Incretins; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2

Topics: Clinical Trials as Topic; Diabetic Nephropathies; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Kidney; Renal Insufficiency, Chronic; Signal Transduction; Treatment Outcome