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.
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.



Participants with HbA1c ≥ 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 HbA1c and LDL cholesterol.



Non-inferiority was demonstrated for both co-primary endpoints: the upper limits of 95% CIs for differences (combination-reference) were less than the prespecified margins of 3.3 mmol/mol (0.3%) for change from baseline in HbA1c [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.



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.
Department of Medicine, Addenbrooke's Hospital, Cambridge, UK.
P
P
Ambery
Clinical Statistics, GlaxoSmithKline, Stevenage, UK.
A
A
Stylianou
Alternative Discovery and Development, GlaxoSmithKline, Brentford, UK.
G
G
Atkinson
Alternative Discovery and Development, GlaxoSmithKline, Brentford, UK.
C
C
Dott
Alternative Discovery and Development, GlaxoSmithKline, Brentford, UK.
L
L
Baylor Curtis
Alternative Discovery and Development, GlaxoSmithKline, Brentford, UK.
N
N
Haque
Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Research Triangle Park, NC, USA.
K
K
LaCroix
Diabetes Centre, Eulji Hospital, Eulji University School of Medicine, Seoul, Republic of Korea.
K W
KW
Min
D000368:Aged; D000069059:Atorvastatin / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000074099:Equivalence Trials as Topic; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*
D000069059:Atorvastatin; D008078:Cholesterol, LDL; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C057619:glimepiride