Sequential Intensification of Metformin Treatment in Type 2 Diabetes With Liraglutide Followed by Randomized Addition of Basal Insulin Prompted by A1C Targets Full Text
Diabetes Care, 05/16/2012
DeVries JH et al. – Supplementation of metformin with liraglutide and then insulin detemir was well tolerated in the majority of patients, with good glycemic control, sustained weight loss, and very low hypoglycemia rates.Methods
- In 988 participants from North America and Europe uncontrolled on metformin ± sulfonylurea, sulfonylurea was discontinued and liraglutide 1.8 mg/day added for 12 weeks (run-in).
- Subsequently, those with A1C ≥7% were randomized 1:1 to 26 weeks’ open-label addition of insulin detemir to metformin + liraglutide (n = 162) or continuation without insulin detemir (n = 161).
- Patients achieving A1C <7% continued unchanged treatment (observational arm).
- The primary end point was A1C change between randomized groups.
- Of 821 participants completing the run-in, 61% (n = 498) achieved A1C <7% (mean change -1.3% from 7.7% at start), whereas 39% (n = 323) did not (-0.6% from 8.3% at start).
- During run-in, 167 of 988 (17%) withdrew; 46% of these due to gastrointestinal adverse events.
- At week 26, A1C decreased further, by 0.5% (from 7.6% at randomization) with insulin detemir (n = 162) versus 0.02% increase without insulin detemir (n = 157) to 7.1 and 7.5%, respectively (estimated treatment difference -0.52 [95% CI -0.68 to -0.36]; P < 0.0001).
- Forty-three percent of participants with insulin detemir versus 17% without reached A1C <7%.
- Mean weight decreased by 3.5 kg during run-in, then by 0.16 kg with insulin detemir or 0.95 kg without insulin detemir.
- In the randomized phase, no major hypoglycemia occurred and minor hypoglycemia rates were 0.286 and 0.029 events per participant-year with and without insulin detemir (9.2 vs. 1.3%).