Data from a long-term study demonstrate that the DPP-IV inhibitor linagliptin effectively manages insulin levels in patients with type 2 diabetes who are not responding to metformin. In addition, linagliptin was associated with significantly fewer adverse effects than second-line sulfonylureas such as glimepiride.
Treatment with sulfonylureas, a common second-line option in patients who do not respond to metformin, can cause weight gain and puts patients at risk for hypoglycemia, myocardial infarction and stroke.
“Since hypoglycemia can have substantial negative clinical consequences in terms of cognitive function, mortality, morbidity, adherence to treatment, and quality of life, its prevention is a crucial component of any diabetes management program,” study researcher Baptist Gallwitz, MD, of Tübingen University Hospital in Germany, said in a press release.
DPP-IV inhibitors such as linagliptin (Tradjenta, Boehringer Ingelheim/Lilly), however, work differently than sulfonylureas, blocking the glucose-producing enzyme DPP-IV and allowing the body to produce the insulin it needs independently of blood glucose.
The 2-year, parallel-group, noninferiority, double blind study assessed outpatients with type 2 diabetes and HbA1C levels between 6.5% and 10% on stable metformin alone or with one additional oral antidiabetic drug. Patients were randomly assigned to once daily oral linagliptin 5 mg (n=777) or glimepiride (Amaryl, Sanofi-Aventis) 1 mg to 4 mg (n=775).
The two treatments produced similar improvements in patients’ glucose regulation (difference, 0.2%; 97.5% CI, 0.09-0.30), but those treated with linagliptin experienced significantly fewer adverse effects compared with those treated with glimepiride. Only 7% of patients treated with linagliptin experienced hypoglycemia vs. the 36% of patients treated with glimepiride.
Those treated with linagliptin also experienced fewer cardiovascular events (RR=0.46; 95% CI, 0.23-0.91) or strokes than those treated with glimepiride, but the researchers said a longer study is needed to confirm linagliptin’s effectiveness on these outcomes.
Disclosure: The study was funded by Boehringer Ingelheim. Dr. Gallwitz reports financial ties to AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Merck, Roche, Sanofi and Takeda.