San Diego, CA—Linagliptin—a dipeptidyl peptidase (DPP)-4 inhibitor—was as effective as glimepiride in lowering blood glucose in patients with type 2 diabetes, and the newer drug demonstrated some safety advantages over glimepiride. It was associated with a lower incidence of hypoglycemia, fewer cardiovascular events, and weight loss instead of weight gain. These were 2-year data from an industry-sponsored, randomized, double-blind, noninferiority study comparing linagliptin with glimepiride in patients with type 2 diabetes inadequately controlled with metformin.
“The difference favoring linagliptin for weight and cardiovascular safety was encouraging. Additionally, linagliptin does not require dose adjustments in patients with renal impairment, unlike other DPP-4 inhibitors. In my view, linagliptin is poised to replace sulfonylureas in the treatment of type 2 diabetes,” said Baptist Gallwitz, MD, Department of Medicine IV and the Outpatient Clinics for Endocrinology, Diabetes, and Metabolism, Eberhard-Karls-University, Tübingen, Germany, at the 71st Scientific Sessions of the American Diabetes Association.
In the study, 1551 patients receiving metformin monotherapy were randomized to receive either add-on linagliptin 5 mg daily or add-on glimepiride 1 to 4 mg daily for a period of 104 weeks. Both groups were well balanced for demographic, disease, and cardiovascular characteristics. Their mean age was 59.8 years, and about 60% were male. The mean waist circumference was 104 cm, and the mean body mass index was 30.2 kg/m2. About 53% of patients had type 2 diabetes for more than 5 years. The mean hemoglobin (Hb)A1c was 7.7%, and the mean fasting blood glucose was 165 mg/dL. Approximately 10% were taking aspirin, 25% were taking antihypertensive drugs, and 11% were taking lipid-lowering drugs.
Both drugs delivered similar long-term benefits in glycemic control. After 104 weeks of treatment, for all patients enrolled in the trial, the mean change in HbA1c from baseline was –0.16 with linagliptin plus metformin versus –0.36 with glimepiride plus metformin. In patients who completed 104 weeks of treatment, the mean change in HbA1c over time was –0.4% versus –0.5%, respectively.
The incidence of hypoglycemia was only 7.5% among those receiving linagliptin versus 36.1% among those receiving glimepiride (P <.0001), a significant difference. Over time, linagliptin was associated with a mean difference of –2.9 kg (about 6 lb) in the change in body weight. Linagliptin was also associated with a 50% relative risk reduction in cardiovascular events versus glimepiride; cardiovascular events (eg, cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina) were observed in 12 patients receiving linagliptin versus 26 patients receiving glimepiride.
Dr Gallwitz said that the cardiovascular safety of linagliptin is being compared with that of other common antidiabetic agents in the long-term Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients with Type 2 Diabetes (CAROLINA). He pointed out that no cardiovascular end points were incorporated in trials of sulfonylureas, yet these drugs are commonly used in clinical practice.
Linagliptin was recently approved by the US Food and Drug Administration to be used along with diet and exercise to lower blood glucose in adults with type 2 diabetes.