Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial

• Published in: Diabetes research and clinical practice Vol. 153; pp. 14 - 22
• Main Authors: Muskiet, M.H.A., Bunck, M.C., Heine, R.J., Cornér, A., Yki-Järvinen, H., Eliasson, B., Joles, J.A., Diamant, M., Tonneijck, L., van Raalte, D.H.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.07.2019
• Subjects: Albuminuria; blood; Diabetes Mellitus; Diabetic kidney disease; Diabetic Nephropathies; drug therapy; Endocrinology and Diabetes; Endokrinologi och diabetes; Exenatide; Female; Glomerular filtration rate; GLP-1 receptor agonist; Humans; Hypoglycemic Agents; Insulin Glargine; Kidney Function Tests; Male; methods; Middle Aged; pathology; pharmacology; Renoprotection; therapeutic use; Type 2; Type 2 diabetes mellitus; urine; Renoprotection; Insulin glargine; GLP-1 receptor agonist; Albuminuria; Type 2 diabetes mellitus; Exenatide; Glomerular filtration rate; Diabetic kidney disease
• ISSN: 0168-8227; 1872-8227; 1872-8227
• DOI: 10.1016/j.diabres.2019.05.001

To compare the effects of long-term treatment with the GLP-1RA exenatide twice-daily versus titrated insulin glargine (iGlar) on renal function and albuminuria in type 2 diabetes (T2DM) patients. We post-hoc evaluated renal outcome-data of 54 overweight T2DM patients (mean  ± SD age 60 ± 8 years, HbA1c 7.5 ± 0.9%, eGFR 86 ± 16 mL/min/1.73 m2, median [IQR] urinary albumin-to-creatinine-ratio (UACR) 0.75 [0.44–1.29] mg/mmol) randomised to exenatide 10 µg twice-daily or titrated iGlar on-top-of metformin for 52-weeks. Renal efficacy endpoints were change in creatinine clearance (CrCl) and albuminuria (urinary albumin-excretion [UAE] and UACR) based on 24-h urines, collected at baseline and Week-52. eGFR and exploratory endpoints were collected throughout the intervention-period, and after a 4-week wash-out. HbA1c-reductions were similar with exenatide (mean ± SEM −0.80 ± 0.10%) and iGlar (−0.79 ± 0.14%; treatment-difference 0.02%; 95% CI −0.31 to 0.42%). Change from baseline to Week-52 in CrCl, UAE or UACR did not statistically differ; only iGlar reduced albuminuria (P < 0.05; within-group). eGFR decreased from baseline to Week-4 with exenatide (−3.9 ± 2.1 mL/min/1.73 m2; P = 0.069) and iGlar (−2.7 ± 1.2 mL/min/1.73 m2; P = 0.034), without treatment-differences in ensuing trajectory. Exenatide versus iGlar reduced bodyweight (−5.4 kg; 2.9–7.9; P < 0.001), but did not affect blood pressure, lipids or plasma uric acid. Among T2DM patients without overt nephropathy, one-year treatment with exenatide twice-daily does not affect renal function-decline or onset/progression of albuminuria compared to titrated iGlar. Trial registration:ClinicalTrials.gov ID: NCT00097500.