Less hypoglycemia with DPP-4 inhibitor added to metformin than with sulfonylurea

Saxagliptin as an add-on to metformin in patients with type 2 diabetes was associated with fewer episodes of hypoglycemia than add-on glipizide in a randomized, double-blind study.
     More patients taking saxagliptin plus metformin achieved glycosylated hemoglobin (HbA_1c) targets without either hypoglycemia or weight gain than did patients on glipizide plus metformin, reported Hakim Bouzamondo, MD, and colleagues from Bristol-Myers Squibb (BMS) in Princeton, New Jersey, makers of saxagliptin.
     “Sulfonylureas like glipizide are associated with hypoglycemia and weight gain. They’re very effective agents, but they have these important side effects, and their effect tends to attenuate over time, so you get a big drop in A_1c that attenuates over time,” said Brian Bryzinski, MD, Senior Director at AstraZeneca in Wilmington, Delaware, in an interview. AstraZeneca is a research partner with BMS, and co-funded the study.
     In a post-hoc analysis from a head-to-head study, the investigators compared the proportion of patients treated with either the selective DPP-4 inhibitor saxagliptin (428) or glipizide (430) who:

Reported hypoglycemic events;

Had baseline HbA_1c from  7% to 8.5% and achieved HbA_1c less than 7% without hypoglycemia; and

Achieved HbA_1c  less than 7% or HbA_1c reductions greater than 0.5% without hypoglycemia or weight gain.

     Patients in the saxagliptin group took the drug in 5-mg doses daily, and patients in the glipizide group received doses titrated from 5 to 20 mg per day, each for 52 weeks as an add-on to metformin.
     The proportion of patients with adverse events (excluding hypoglycemia) in the 2 treatment groups was similar; more patients took glipizide than saxagliptin.
     Among patients with baseline HbA_1c from 7% to 8.5% who achieved HbA_1c less than 7%, 49.2% of those taking saxagliptin did so without a hypoglycemic episode, compared with 33.1% of those taking glipizide (P not shown).
     Among all patients with baseline HbA_1c 7% or higher, 26.6% of those taking saxagliptin versus 13.8% of those taking glipizide were able to achieve HbA_1c less than 7% without hypoglycemia or weight gain.
     Similarly, the proportion of patients who achieved HbA_1c reductions greater than 0.5% without experiencing either hypoglycemia or weight gain was higher among patients taking saxagliptin than among those on glipizide (33.2% vs. 14.7%).