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Open‐label randomized non‐inferiority trial of a fixed‐dose combination of glimepiride and atorvastatin for the treatment of people whose Type 2 diabetes is uncontrolled on metformin
Author(s) -
Ambery P.,
Stylianou A.,
Atkinson G.,
Dott C.,
Baylor Curtis L.,
Haque N.,
LaCroix K.,
Min K. W.
Publication year - 2016
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.13003
Subject(s) - glimepiride , medicine , atorvastatin , type 2 diabetes , metformin , fixed dose combination , randomized controlled trial , adverse effect , bioequivalence , diabetes mellitus , gastroenterology , urology , pharmacology , endocrinology , pharmacokinetics
Aims To evaluate, in a randomized, open‐label study, the non‐inferiority of a bioequivalent fixed‐dose combination of glimepiride and atorvastatin vs. separately co‐administered tablets in people with Type 2 diabetes mellitus. Methods Participants with HbA 1c ≥ 53 to < 80 mmol/mol (≥ 7.0 to < 9.5%), average fasting blood glucose > 7.0 mmol/l, who were on metformin for ≥ 3 months, were randomized to combination ( n = 215) or co‐administered glimepiride and atorvastatin ( n = 212) once daily for 20 weeks. Up‐titration of glimepiride (1–4 mg) and atorvastatin (10–20 mg) were based on average fasting blood glucose and LDL cholesterol, respectively. Co‐primary endpoints were change from baseline to week 20 in HbA 1c and LDL cholesterol. Results Non‐inferiority was demonstrated for both co‐primary endpoints: the upper limits of 95% CI s for differences (combination‐reference) were less than the prespecified margins of 3.3 mmol/mol (0.3%) for change from baseline in HbA 1c [difference 0.1 mmol/mol (95% CI −1.6, 1.9); 0.01% (95% CI −0.15, 0.17)] and 6% for percentage change from baseline in LDL cholesterol [difference 0.87% (95% CI −2.47, 4.21)]. Similar proportions of participants on combination and reference had treatment‐emergent adverse events (64 vs. 61%). More participants on combination had hypoglycaemia (21 vs. 13%); most events were considered by the treating physician to be unrelated to study drug. Conclusions The combination was non‐inferior to separately co‐administered tablets and the safety profile was consistent with the known profiles of glimepiride and atorvastatin. The observed increase in hypoglycaemia on the combination cannot be explained, but may be attributable to non‐systematic collectiof glucose readings and may have been influenced by reporting bias in this open‐label trial.