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Diabetes Care. 2016 Feb;39(2):222-30. doi: 10.2337/dc14-2883. Epub 2015 Dec 17.

Efficacy and Safety of Liraglutide Versus Placebo as Add-on to Glucose-Lowering Therapy in Patients With Type 2 Diabetes and Moderate Renal Impairment (LIRA-RENAL): A Randomized Clinical Trial.

Author information

1
Diabetes Research Centre, University of Leicester, Leicester, U.K. melanie.davies@uhl-tr.nhs.uk.
2
Institute of Life Science, Swansea University, Swansea, U.K.
3
Qatar Foundation, Weill Cornell Medical College, Doha, Qatar.
4
Steno Diabetes Center, Gentofte, Denmark.
5
Clinical Research Development Associates, Rosedale, NY.
6
Department of Diabetic Nephropathy, Endocrinology Research Centre, Moscow, Russia.
7
Novo Nordisk A/S, Søborg, Denmark.
8
Division of Endocrinology, Metabolism and Lipids, Emory University, Atlanta, GA.

Abstract

OBJECTIVE:

Renal impairment in type 2 diabetes limits available glucose-lowering treatment options. This trial was conducted to establish the efficacy and safety of liraglutide as an add-on to existing glucose-lowering medications in patients with inadequately controlled type 2 diabetes and moderate renal impairment.

RESEARCH DESIGN AND METHODS:

In this 26-week, double-blind trial, 279 patients with HbA1c 7-10%, BMI 20-45 kg/m(2), and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2); MDRD) were randomized (1:1) to once-daily liraglutide 1.8 mg (n = 140) or placebo (n = 139).

RESULTS:

The estimated treatment difference in HbA1c from baseline to week 26 was -0.66% (-7.25 mmol/mol) (95% CI -0.90 to -0.43 [-9.82 to -4.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (-1.22 mmol/L [-22.0 mg/dL]) than with placebo (-0.57 mmol/L [-10.3 mg/dL], P = 0.036). There was a greater reduction in body weight with liraglutide (-2.41 kg) than with placebo (-1.09 kg, P = 0.0052). No changes in renal function were observed (eGFR relative ratio to baseline: -1% liraglutide, +1% placebo; estimated treatment ratio [ETR] 0.98, P = 0.36). The most common adverse events were gastrointestinal (GI) adverse effects (liraglutide, 35.7%; placebo, 17.5%). No difference in hypoglycemic episodes was observed between treatment groups (event rate/100 patient-years of exposure: liraglutide, 30.47; placebo, 40.08; P = 0.54). The estimated ratio to baseline for lipase was 1.33 for liraglutide and 0.97 for placebo (ETR 1.37, P < 0.0001).

CONCLUSIONS:

Liraglutide did not affect renal function and demonstrated better glycemic control, with no increase in hypoglycemia risk but with higher withdrawals due to GI adverse events than placebo in patients with type 2 diabetes and moderate renal impairment.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01620489.

PMID:
26681713
DOI:
10.2337/dc14-2883
[Indexed for MEDLINE]

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