Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study.
OBJECTIVE
To show that vildagliptin added to metformin is non-inferior to glimepiride in reducing HbA1c levels from baseline over 2 years.


METHODS
A randomized, double-blind, active-comparator study of patients with type 2 diabetes mellitus inadequately controlled (HbA1c 6.5-8.5%) by metformin monotherapy. Patients received vildagliptin (50 mg twice daily) or glimepiride (up to 6 mg/day) added to metformin.


RESULTS
In all, 3118 patients were randomized (vildagliptin, n = 1562; glimepiride, n = 1556). From similar baseline values (7.3%), after 2 years adjusted mean (s.e.) change in HbA1c was comparable between vildagliptin and glimepiride treatment: -0.1% (0.0%) and -0.1% (0.0%), respectively. The primary objective of non-inferiority was met. A similar proportion of patients reached HbA1c <7% (36.9 and 38.3%, respectively), but with vildagliptin more patients reached this target without hypoglycaemia (36.0% vs. 28.8%; p = 0.004). The initial response (IR) was sustained for a mean (s.d.) of 309 (244) days with vildagliptin versus 270 (223) days for glimepiride (p < 0.001) (IR = nadir HbA1c where change from baseline > or =0.5% or HbA1c < or =6.5% within the first six months of treatment. After IR was detected, sustained response = time between nadir and an increase of >0.3% above IR). Independent of disease duration, age was a predictor of effect sustainability. Fewer patients experienced hypoglycaemia with vildagliptin (2.3% vs. 18.2% with glimepiride) with a 14-fold difference in the number of hypoglycaemic events (59 vs. 838). Vildagliptin had a beneficial effect on body weight [mean (s.e.) change from baseline -0.3 (0.1) kg; between-group difference -1.5 kg; p < 0.001]. Overall, both treatments were well tolerated and displayed similar safety profiles.


CONCLUSIONS
Vildagliptin add-on has similar efficacy to glimepiride after 2 years' treatment, with markedly reduced hypoglycaemia risk and no weight gain.
Matthews
D R
DR
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital and NIHR, Oxford Biomedical Research Centre, UK. david.matthews@ocdem.ox.ac.uk
Dejager
S
S
Ahren
B
B
Fonseca
V
V
Ferrannini
E
E
Couturier
A
A
Foley
J E
JE
Zinman
B
B
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001835:Body Weight / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000008:administration & dosage*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D016896:Treatment Outcome; D000077597:Vildagliptin; D015430:Weight Gain; D055815:Young Adult
D000218:Adamantane; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D009570:Nitriles; D011759:Pyrrolidines; D013453:Sulfonylurea Compounds; D000077597:Vildagliptin; C057619:glimepiride