Insulin glargine as a second-line treatment after metformin in patients with type 2 diabetes is superior to adding the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin to achieve glycemic control, according to a first randomized head-to-head comparison of a DPP-4 and basal insulin presented at the 2012 ADA annual meeting.
The study showed that the reduction in hemoglobin (Hb) A1c was greater with insulin glargine than with the DPP-4 sitagliptin, reported principal investigator Pablo J. Aschner, MD, MSc, Professor, Department of Endocrinology, Javeriana Pontificia University, Colombia. The results of this study were simultaneously published in the Lancet (Aschner PJ, et al. Lancet. 2012; 379:2262-2269).
Long-Term Benefits with Early Basal Insulin
“The results of this study support the option of introducing basal insulin (glargine) in patients with type 2 diabetes who are inadequately controlled by metformin, with the potential for long-term benefits arising from the achievement of optimum glycemic control early in the course of the disease,” Dr Aschner said.
This open-label study demonstrated that patients assigned to insulin glargine were 60% more likely to achieve an HbA1c level <7% than those assigned to sitagliptin, “with concurrently lower fasting and postprandial blood glucose.”
The trial included 515 metformin-treated patients with type 2 diabetes whose HbA1c level was between 7% and 11% while receiving metformin. The patients were randomized to insulin glargine, starting at 0.2 U/kg injected at dinner or bedtime, or to sitagliptin 100 mg daily. The dosage of insulin glargine was adjusted according to patients’ self-monitored fasting plasma glucose (FPG) concentration to maintain FPG between 4.0 mmol/L and 5.5 mmol/L.
At 24 weeks, the adjusted mean reduction in HbA1c level in the modified intent-to-treat patient population was 1.72% in the patients assigned to insulin glargine and 1.13% in those assigned to sitagliptin, with a final mean HbA1c concentration of 6.8% in the insulin glargine group versus 7.4% in the sitagliptin group.
At the last available visit during study treatment in which HbA1c level was measured, 68% of insulin glargine users versus 42% of sitagliptin users achieved a target of <7% HbA1c.
The adjusted mean difference in self-monitored FPG between the 2 groups was 2.3 mmol/L (41 mg/dL) in favor of insulin glargine.
Advantages of DPP-4 Inhibitors
“As expected, the estimated rate of hypoglycemia per patient-year was 8 times higher with glargine, but the risk of severe events, although also 3 times higher, was not significantly different from that with sitagliptin,” said Dr Aschner.
The rates of hypoglycemia were 46% with insulin glargine compared with 13% for sitagliptin. Symptomatic hypoglycemia occurred more often in the insulin glargine recipients, and severe symptomatic hypoglycemia was rare in either group—1% of the insulin glargine group and <1% in the sitagliptin group. The risk for severe nocturnal hypoglycemia was <1% in each group.
Body weight declined by a mean of 1.08 kg from baseline in the sitagliptin group but increased by a mean of 0.44 kg in the insulin glargine group, for an adjusted mean difference of 1.51 kg (P <.001).
There were no new safety signals observed with insulin glargine in the study.
“Results show that if people learn to titrate basal insulin and do not have episodes of severe hypoglycemia, more of them might continue over time to reach their glycemic goal with the combination of insulin glargine plus metformin,” concluded Dr Aschner.