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

Melanie J. Davies, Stephen C. Bain, Stephen Atkin, Peter Rossing, David Scott, Minara S. Shamkhalova, Heidrun Bosch-Traberg, Annika Syrén, Guillermo E. Umpierrez

Research output: Contribution to journalArticle

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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/m2, and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m2; 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 20.66% (27.25 mmol/mol) (95% CI 20.90 to 20.43 [29.82 to 24.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (21.22 mmol/L [222.0 mg/dL]) than with placebo (20.57mmol/L [210.3mg/dL], P = 0.036). Therewas a greater reduction in body weight with liraglutide (22.41 kg) thanwith placebo (21.09 kg, P = 0.0052).No changes in renal function were observed (eGFR relative ratio to baseline:21% 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.

Original languageEnglish
Pages (from-to)222-230
Number of pages9
JournalDiabetes Care
Volume39
Issue number2
DOIs
Publication statusPublished - 1 Feb 2016
Externally publishedYes

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Type 2 Diabetes Mellitus
Randomized Controlled Trials
Placebos
Kidney
Safety
Glucose
Therapeutics
Glomerular Filtration Rate
Liraglutide
Lipase
Hypoglycemia
Hypoglycemic Agents
Fasting
Research Design
Body Weight

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

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. / Davies, Melanie J.; Bain, Stephen C.; Atkin, Stephen; Rossing, Peter; Scott, David; Shamkhalova, Minara S.; Bosch-Traberg, Heidrun; Syrén, Annika; Umpierrez, Guillermo E.

In: Diabetes Care, Vol. 39, No. 2, 01.02.2016, p. 222-230.

Research output: Contribution to journalArticle

Davies, Melanie J. ; Bain, Stephen C. ; Atkin, Stephen ; Rossing, Peter ; Scott, David ; Shamkhalova, Minara S. ; Bosch-Traberg, Heidrun ; Syrén, Annika ; Umpierrez, Guillermo E. / 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. In: Diabetes Care. 2016 ; Vol. 39, No. 2. pp. 222-230.
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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/m2, and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m2; 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 20.66{\%} (27.25 mmol/mol) (95{\%} CI 20.90 to 20.43 [29.82 to 24.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (21.22 mmol/L [222.0 mg/dL]) than with placebo (20.57mmol/L [210.3mg/dL], P = 0.036). Therewas a greater reduction in body weight with liraglutide (22.41 kg) thanwith placebo (21.09 kg, P = 0.0052).No changes in renal function were observed (eGFR relative ratio to baseline:21{\%} 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.",
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T2 - A randomized clinical trial

AU - Davies, Melanie J.

AU - Bain, Stephen C.

AU - Atkin, Stephen

AU - Rossing, Peter

AU - Scott, David

AU - Shamkhalova, Minara S.

AU - Bosch-Traberg, Heidrun

AU - Syrén, Annika

AU - Umpierrez, Guillermo E.

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N2 - 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/m2, and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m2; 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 20.66% (27.25 mmol/mol) (95% CI 20.90 to 20.43 [29.82 to 24.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (21.22 mmol/L [222.0 mg/dL]) than with placebo (20.57mmol/L [210.3mg/dL], P = 0.036). Therewas a greater reduction in body weight with liraglutide (22.41 kg) thanwith placebo (21.09 kg, P = 0.0052).No changes in renal function were observed (eGFR relative ratio to baseline:21% 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.

AB - 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/m2, and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m2; 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 20.66% (27.25 mmol/mol) (95% CI 20.90 to 20.43 [29.82 to 24.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (21.22 mmol/L [222.0 mg/dL]) than with placebo (20.57mmol/L [210.3mg/dL], P = 0.036). Therewas a greater reduction in body weight with liraglutide (22.41 kg) thanwith placebo (21.09 kg, P = 0.0052).No changes in renal function were observed (eGFR relative ratio to baseline:21% 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.

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