exenatide and Albuminuria

To evaluate the albuminuria-lowering effect of dapagliflozin, exenatide, and the combination of dapagliflozin and exenatide in patients with type 2 diabetes and microalbuminuria or macroalbuminuria.. We enrolled 20 patients, who completed 53 treatment periods in total. Mean percentage change in UACR from baseline was -21.9% (95% CI: -34.8% to -6.4%) during dapagliflozin versus -7.7% (95% CI: -23.5% to 11.2%) during exenatide and -26.0% (95% CI: -38.4% to -11.0%) during dapagliflozin-exenatide treatment. No correlation was observed in albuminuria responses between the different treatments. Numerically greater reductions in systolic blood pressure, body weight and eGFR were observed during dapagliflozin-exenatide treatment compared with dapagliflozin or exenatide alone. Renal blood flow and effective renal plasma flow (ERPF) did not significantly change with either treatment regimen. However, all but four and two patients in the dapagliflozin and dapagliflozin-exenatide groups, respectively, showed reductions in ERPF. The filtration fraction did not change during treatment with dapagliflozin or exenatide, and decreased during dapagliflozin-exenatide treatment (-1.6% [95% CI: -3.2% to -0.01%]; P = .048).. In participants with type 2 diabetes and albuminuria, treatment with dapagliflozin, exenatide and dapagliflozin-exenatide reduced albuminuria, with a numerically larger reduction in the combined dapagliflozin-exenatide treatment group.

Topics: Albuminuria; Benzhydryl Compounds; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glomerular Filtration Rate; Humans

To assess whether the previously developed multivariable risk prediction framework (PRE score) could predict the renal effects observed in the EXSCEL cardiovascular outcomes trial using short-term changes in cardio-renal risk markers.. Changes from baseline to 6 months in HbA1c, systolic blood pressure (SBP), body mass index (BMI), haemoglobin, total cholesterol, and new micro- or macroalbuminuria were evaluated. The renal outcomes were defined as a composite of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD). Relationships between risk markers and long-term renal outcomes were determined in patients with type 2 diabetes from the ALTITUDE study using multivariable Cox regression analysis, and then applied to short-term changes in risk markers observed in EXSCEL to predict the exenatide-induced impact on renal outcomes.. Compared with placebo, mean HbA1c, BMI, SBP and total cholesterol were lower at 6 months with exenatide, as was the incidence of new microalbuminuria. The PRE score predicted a relative risk reduction for the 30% eGFR decline + ESRD endpoint of 11.3% (HR 0.89; 95% CI 0.83-0.94), compared with 12.7% (HR 0.87; 0.77-0.99) observed risk reduction. For the 40% eGFR decline + ESRD endpoint, the predicted and observed risk reductions were 11.0% (HR 0.89; 0.82-0.97) and 13.7% (HR 0.86, 0.72-1.04), respectively.. Integrating short-term risk marker changes into a multivariable risk score predicted the magnitude of renal risk reduction observed in EXSCEL.

Topics: Albuminuria; Diabetes Mellitus, Type 2; Disease Progression; Exenatide; Glomerular Filtration Rate; Humans; Kidney Diseases; Risk Factors

To examine the albuminuria-lowering effect of exenatide once weekly (EQW) compared with active glucose-lowering comparators in patients with type 2 diabetes and elevated urinary albumin-to-creatinine ratio (uACR).. Six randomized double-blind and open-label phase III studies were pooled in a post hoc, exploratory analysis to evaluate the efficacy and safety of EQW versus non-glucagon-like peptide-1 receptor agonist comparators in patients with type 2 diabetes and baseline uACR ≥30 mg/g. Treatment groups were EQW versus all comparators pooled. Efficacy outcomes were percent change from baseline to week 26/28 in uACR and absolute change in glycated haemoglobin (HbA1c), systolic blood pressure (SBP), body weight and estimated glomerular filtration rate (eGFR).. Baseline characteristics were generally similar between the two treatment groups (EQW: N = 194, all comparators: N = 274). Relative to the comparator group, EQW changed albuminuria by -26.2% (95% confidence interval [CI] -39.5 to -10). Similar improvements were observed with EQW versus oral glucose-lowering drugs (-29.6% [95% CI -47.6 to -5.3) or insulin (-23.8% [95% CI -41.8 to -0.2]). The effect of EQW on uACR was independent of baseline renin-angiotensin system inhibitor usage. Adjusted mean decreases in HbA1c, SBP and body weight were more pronounced in the EQW versus the comparator group. Adjustment for changes in HbA1c, eGFR and SBP did not substantially affect the uACR-lowering effect of EQW. When also adjusting for changes in body weight, the uACR-lowering effect was reduced to (-13.0% [95% CI -29.9 to 7.8]).. Exenatide once weekly reduced uACR in patients with type 2 diabetes and elevated albuminuria compared to commonly used glucose-lowering drugs.

Topics: Albumins; Albuminuria; Diabetes Mellitus, Type 2; Exenatide; Humans; Hypoglycemic Agents; Pharmaceutical Preparations

Cardiovascular outcomes in clinical trials with type 2 diabetes mellitus (T2DM) patients have shown that glucagon-like peptide-1 receptor agonist can have a beneficial effect on the kidney. This trial aimed to assess the effects of exenatide on renal outcomes in patients with T2DM and diabetic kidney disease (DKD).. We performed a randomized parallel study encompassing 4 general hospitals. T2DM patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and macroalbuminuria, defined as 24-h urinary albumin excretion rate (UAER) >0.3 g/24 h were randomized 1:1 to receive exenatide twice daily plus insulin glargine (intervention group) or insulin lispro plus glargine (control group) for 24 weeks. The primary outcome was the UAER percentage change from the baseline after 24 weeks of intervention. The rates of hypoglycemia, adverse events (AEs), and change in eGFR during the follow-up were measured as safety outcomes.. Between March 2016 and April 2019, 92 patients were randomized and took at least 1 dose of the study drug. The mean age of the participants was 56 years. At baseline, the median UAER was 1,512.0 mg/24 h and mean eGFR was 70.4 mL/min/1.73 m2. After 24 weeks of treatment, the UAER percentage change was significantly lower in the intervention group than in the control group (p = 0.0255). Moreover, the body weight declined by 1.3 kg in the intervention group (the difference between the 2 groups was 2.7 kg, p = 0.0001). Compared to the control group, a lower frequency of hypoglycemia and more gastrointestinal AEs were observed in the intervention group.. Exenatide plus insulin glargine treatment for 24 weeks resulted in a reduction of albuminuria in T2DM patients with DKD.

Topics: Albuminuria; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Drug Therapy, Combination; Exenatide; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Treatment Outcome

Glycemic variability may contribute to adverse medical outcomes of type 2 diabetes, but prior therapies have had limited success in controlling glycemic fluctuations, and the hypothesis has not been adequately tested.. People with insulin-requiring type 2 diabetes and high cardiovascular risk were enrolled during a run-in period on basal-bolus insulin (BBI), and 102 were randomized to continued BBI or to basal insulin with a prandial GLP-1 receptor agonist (GLIPULIN) group, each seeking to maintain HbA(1c) levels between 6.7% and 7.3% (50-56 mmol/mol) for 6 months. The primary outcome measure was glycemic variability assessed by continuous glucose monitoring; other measures were HbA(1c), weight, circulating markers of inflammation and cardiovascular risk, albuminuria, and electrocardiographic patterns assessed by Holter monitoring.. At randomization, the mean age of the population was 62 years, median duration of diabetes 15 years, mean BMI 34 kg/m(2), and mean HbA(1c) 7.9% (63 mmol/mol). Thirty-three percent had a prior cardiovascular event, 18% had microalbuminuria, and 3% had macroalbuminuria. At baseline, the continuous glucose monitoring coefficient of variation for glucose levels was similar in both groups.. FLAT-SUGAR is a proof-of-concept study testing whether, in a population of individuals with type 2 diabetes and high cardiovascular risk, the GLIPULIN regimen can limit glycemic variability more effectively than BBI, reduce levels of cardiovascular risk markers, and favorably alter albuminuria and electrocardiographic patterns. We successfully randomized a population that has sufficient power to answer the primary question, address several secondary ones, and complete the protocol as designed.

Topics: Albuminuria; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exenatide; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Peptides; Postprandial Period; Risk Factors; Time Factors; Venoms

It was reported that exenatide ameliorated renal injury in diabetic rats. The present study was carried out to evaluate the effect of exenatide on 24-hour urinary albumin, urinary transforming growth factor-β(1) (TGF-β(1)) and type IV collagen excretion in patients with type 2 diabetes and microalbuminuria.. 31 type 2 diabetic patients with microalbuminuria were randomly allocated to receive exenatide (group Exe, n = 13) or glimepiride treatment (group Glm, n = 18) for 16 weeks. Body mass index (BMI), fasting plasma glucose, 2-hour postprandial plasma glucose, glycated hemoglobin A(1c), systolic blood pressure, diastolic blood pressure, 24-hour urinary albumin, urinary TGF-β(1) and type IV collagen concentration were analyzed between the two treatment groups. 20 age- and BMI-matched healthy subjects were chosen as the normal control group (group NC, n = 20).. After 16 weeks of treatment, 24-hour urinary albumin, urinary TGF-β(1) and type IV collagen in group Exe were significantly lower than those of group Glm (p < 0.01), while glycemic control had no statistical difference between the two groups.. Our results indicate that exenatide reduces urinary TGF-β(1) and type IV collagen excretion in patients with type 2 diabetes and microalbuminuria, which may be partly contributory to its directly renoprotective role.

Topics: Adult; Aged; Albuminuria; Biomarkers; Collagen Type IV; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Peptides; Transforming Growth Factor beta1; Venoms

The role of exendin-4 in brown adipose tissue (BAT) activation was not very clear. This study is to verify the role of BAT involved in renal benefits of exendin-4 in diabetes mellitus (DM).. In vivo, C57BL/6 mice were randomly divided into nondiabetic (control) and diabetic groups (DM). The diabetic mice were randomized into a control group (DM-Con), BAT-excision group (DM+Exc), exendin-4-treated group (DM+E4), and BAT-excision plus exendin-4-treated group (DM+Exc+E4). The weight, blood glucose and lipids, 24 h urine albumin and 8-OH-dG, and renal fibrosis were analyzed. In vitro, we investigated the role of exendin-4 in the differentiation process of 3T3-L1 and brown preadipocytes and its effect on the rat mesangial cells induced by oleate.. The expressions of UCP-1, PGC-1. Exendin-4 could decrease the renal lipid deposit and improve diabetic nephropathy via activating the renal AMPK pathway independent of BAT activation.

Topics: 3T3-L1 Cells; 8-Hydroxy-2'-Deoxyguanosine; Adenylate Kinase; Adipocytes, Brown; Adipogenesis; Adipose Tissue, Brown; Albuminuria; Animals; Blood Glucose; Blotting, Western; Body Weight; CD36 Antigens; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Exenatide; Fibrosis; Gene Expression; Incretins; Kidney; Lipase; Mesangial Cells; Mice; Mice, Inbred C57BL; Myofibroblasts; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Random Allocation; Rats; Real-Time Polymerase Chain Reaction; Triglycerides; Uncoupling Protein 1

Kidney disease is common among patients with type 2 diabetes (T2DM). Treatment of diabetes seeks to minimize negative kidney impact.. To assess the changes in kidney function and incidence of albuminuria in patients with T2DM treated for 1 year with exenatide twice daily (BID) or insulin glargine.. Retrospective analyses were performed using an electronic medical record database. Patients inititating treatment with either exenatide BID or insulin glargine between November 2006, and April 2009 comprised the study cohort. The 2 groups were 1:1 propensity score matched on baseline variables yielding 2683 pairs. Measures of kidney function included estimated glomerular filtration rate (eGFR,) and urinary albumin/creatinine ratio (UACR).. Mean baseline eGFR was identical between the groups (79 ± 23 mL/min/1.73 m(2)). At 1-year follow-up, there was no significant difference in mean eGFR between the groups (78 mL/min/1.73 m(2) for exenatide BID vs 80 mL/min/1.73 m(2) for insulin glargine; P = .39). Despite matching of multiple characteristics, mean baseline UACR was lower in the exenatide BID group (mean = 34 ± 71 mg/g) compared with the insulin glargine group (183 ± 509 mg/g; P = .03). At follow-up, exenatide BID patients had a mean increase in UACR of 104 mg/g, insulin glargine patients had a decrease of 47 mg/g, but the difference was not significant (P = .19).. There were no significant differences in change in kidney function or albuminuria at 1 year in patients treated with exenatide BID compared with insulin glargine as administered in routine practice.

Topics: Aged; Albuminuria; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Kidney; Male; Middle Aged; Peptides; Retrospective Studies; Treatment Outcome; Venoms