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

Aims: 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. Methods: 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. Results: 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. Conclusions: 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.