Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.
OBJECTIVE
To evaluate the efficacy and safety of the potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin administered as add-on therapy to metformin in patients with type 2 diabetes with inadequate glycaemic control.


METHODS
This 24-week, randomized, placebo-controlled, double-blind, parallel-group study was carried out in 82 centres in 10 countries. Patients with HbA1c levels of 7.0-10.0% on metformin and a maximum of one additional antidiabetes medication, which was discontinued at screening, continued on metformin ≥1500 mg/day for 6 weeks, including a placebo run-in period of 2 weeks, before being randomized to linagliptin 5 mg once daily (n = 524) or placebo (n = 177) add-on. The primary outcome was the change from baseline in HbA1c after 24 weeks of treatment, evaluated with an analysis of covariance (ANCOVA).


RESULTS
Mean baseline HbA1c and fasting plasma glucose (FPG) were 8.1% and 9.4 mmol/l, respectively. Linagliptin showed significant reductions vs. placebo in adjusted mean changes from baseline of HbA1c (-0.49 vs. 0.15%), FPG (-0.59 vs. 0.58 mmol/l) and 2hPPG (-2.7 vs. 1.0 mmol/l); all p < 0.0001. Hypoglycaemia was rare, occurring in three patients (0.6%) treated with linagliptin and five patients (2.8%) in the placebo group. Body weight did not change significantly from baseline in both groups (-0.5 kg placebo, -0.4 kg linagliptin).


CONCLUSIONS
The addition of linagliptin 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin resulted in a significant and clinically meaningful improvement in glycaemic control without weight gain or increased risk of hypoglycaemia.
Department of Medicine, Helsinki University Central Hospital, Finland. marja-riitta.taskinen@helsinki.fi
M-R
MR
Taskinen
J
J
Rosenstock
I
I
Tamminen
R
R
Kubiak
S
S
Patel
K A
KA
Dugi
H-J
HJ
Woerle
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000069476:Linagliptin; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D011687:Purines / Q000008:administration & dosage* / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage* / Q000494:pharmacology; D055815:Young Adult
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D008687:Metformin; D011687:Purines; D011799:Quinazolines