Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial - PubMed (original) (raw)

Clinical Trial

. 2015 Oct;17(10):936-48.

doi: 10.1111/dom.12503. Epub 2015 Jul 14.

Affiliations

Clinical Trial

Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial

J Rosenstock et al. Diabetes Obes Metab. 2015 Oct.

Abstract

Aims: To investigate the efficacy and tolerability of empagliflozin added to basal insulin-treated type 2 diabetes.

Methods: Patients inadequately controlled [glycated haemoglobin (HbA1c) >7 to ≤10% (>53 to ≤86 mmol/mol)] on basal insulin (glargine, detemir, NPH) were randomized to empagliflozin 10 mg (n = 169), empagliflozin 25 mg (n = 155) or placebo (n = 170) for 78 weeks. The baseline characteristics were balanced among the groups [mean HbA1c 8.2% (67 mmol/mol), BMI 32.2 kg/m(2) ]. The basal insulin dose was to remain constant for 18 weeks, then could be adjusted at investigator's discretion. The primary endpoint was change from baseline in HbA1c at week 18. Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78.

Results: At week 18, the adjusted mean ± standard error changes from baseline in HbA1c were 0.0 ± 0.1% (-0.1 ± 0.8 mmol/mol) for placebo, compared with -0.6 ± 0.1% (-6.2 ± 0.8 mmol/mol) and -0.7 ± 0.1% (-7.8 ± 0.8 mmol/mol) for empagliflozin 10 and 25 mg, respectively (both p < 0.001). At week 78, empagliflozin 10 and 25 mg significantly reduced HbA1c, insulin dose and weight vs placebo (all p < 0.01), and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo (p = 0.004). Similar percentages of patients had confirmed hypoglycaemia in all groups (35-36%). Events consistent with urinary tract infection were reported in 9, 15 and 12% of patients on placebo, empagliflozin 10 and 25 mg, and events consistent with genital infection were reported in 2, 8 and 5%, respectively.

Conclusions: Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo.

Keywords: SGLT2 inhibitor; empagliflozin; type 2 diabetes.

© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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Figures

Figure 1

Figure 1

Effect of empagliflozin on efficacy parameters at week 18. (A) change from baseline in glycated haemoglobin [

HbA1c

; analyis of covariance (

ancova

), full analysis set (

FAS

) week 18 completers, last observation carried forward (

LOCF

) imputation]; (B) change from baseline in fasting plasma glucose (

FPG

;

ancova

,

FAS

,

LOCF

); (C) change from baseline in body weight (

ancova

,

FAS

,

LOCF

); (D) change from baseline in systolic blood pressure (

SBP

;

ancova

,

FAS

,

LOCF

); (E) change from baseline in diastolic blood pressure (

DBP

;

ancova

,

FAS

,

LOCF

). Data are adjusted mean ± standard error. *p < 0.001 vs placebo; †p = 0.035 vs placebo; ‡p = 0.011 vs placebo; §p = 0.027 vs placebo.

Figure 2

Figure 2

Effect of empagliflozin on efficacy parameters at week 78. (A) Glycated haemoglobin (

HbA1c

) over time [mixed model repeated measures (

MMRM

), full analysis set (

FAS

), observed cases (

OC

)]; (B) change from baseline in

HbA1c

[analysis of covariance (

ancova)

,

FAS

week 78 completers, last observation carried forward (

LOCF

) imputation]; (C) fasting plasma glucose (

FPG

) over time (

MMRM

,

FAS

,

OC

); (D) change from baseline in

FPG

(

ancova

,

FAS

,

LOCF

); (E) basal insulin dose over time (

MMRM

,

FAS

,

OC

); (F) change from baseline in basal insulin dose at week 78 (

ancova

,

FAS

‐78 completers,

LOCF

); (G) body weight over time (

MMRM

,

FAS

,

OC

); (H) change from baseline in body weight (

ancova

,

FAS

,

LOCF

); (I) change from baseline in

SBP

(

ancova

,

FAS

,

LOCF

); (J) change from baseline in

DBP

(

ancova

,

FAS

,

LOCF

). Data are mean ± standard error (s.e.) at baseline and adjusted mean ± s.e. on treatment. *p < 0.001 vs placebo; †p = 0.005 vs placebo; §p = 0.002 vs placebo; ‡p = 0.009 vs placebo; ¶p = 0.004 vs placebo.

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