PHILADELPHIA – Introduction of basal insulin glargine for patients with type 2 diabetes who were uncontrolled on metformin was associated with improved glycemic control compared with the addition of sitagliptin in a 24-week, multicenter, open-label trial of more than 500 patients.
However, glargine was associated with a greater degree of weight gain and significantly greater rates of hypoglycemia, although severe hypoglycemia rates were rare, Dr. Pablo J. Aschner reported.
The study, funded by Sanofi, is the first randomized trial to compare two glucose-lowering treatment options that are often considered as second-line add-on treatment to metformin, in real-world conditions. "The results of this study support the option of introduction of basal insulin in patients with type 2 diabetes 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," said Dr. Aschner, an endocrinologist and clinical epidemiologist, and professor of endocrinology and director of research at Javeriana University Hospital, Bogotá, Colombia.
The findings were simultaneously published online (Lancet 2012 June 9 [doi:10.1016/S0140-6736(12)60439-5]).
In the Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-Naive Patients (EASIE) study, 250 patients were randomized to glargine in doses starting at 0.2 units per kg of body weight injected at dinner or bedtime with a prefilled pen, and titrated up or down based on self-monitored blood glucose levels. The 265 patients in the sitagliptin group received a fixed oral dose of 100 mg once daily taken in the morning and no changes in dose were allowed during the trial. The patients, 480 of whom completed the trial (227 glargine/253 sitagliptin), were aged 35-70 years, diagnosed with type 2 diabetes for at least 6 months, and had hemoglobin A1c values between 7% and 11% while on metformin therapy.
HbA1c, 8.5% for both groups at baseline, was reduced to a significantly greater extent with insulin glargine than with sitagliptin throughout the study, with mean reductions of 1.72 versus 1.13 percentage points. At 24 weeks, more patients in the glargine group had achieved A1c levels below 7% (68% versus 42%) compared with those in the sitagliptin group. The story was similar for HbA1c levels of less than 6.5% (40% vs. 17%). Patients in the glargine group also had significantly greater reductions in self-monitored fasting plasma glucose, with an adjusted mean difference between groups of 41.2 mg/dL, Dr. Aschner reported.
Glargine doses increased throughout the study, from 0.19 units/kg at baseline to 0.45 units/kg at 12 weeks and then leveling off to 0.5 units/kg at 24 weeks, at which point patients were taking an average of 41.4 units/day.
Body weight increased by 0.44 kg in the insulin glargine group and decreased by 1.08 kg in the sitagliptin group, a significant difference. More patients in the glargine group had one or more episodes of symptomatic hypoglycemia (46% vs. 54%). Glargine was associated with 8.45 times more hypoglycemic events per patient-year than was sitagliptin (4.21 vs. 0.5 events/patient-year). Severe hypoglycemia was 3.4-fold more common with glargine, although it was rare in both groups (1% with glargine and less than 1% with sitagliptin). The incidence of other treatment-emergent adverse events did not differ between the groups.
In all, Dr. Aschner noted, these findings suggest that glycemic control can be achieved with an average supplementary dose of 0.5 units per kg of insulin glargine and a weight gain of less than 0.5 kg. The results of this study are in general agreement with previous results for both insulin glargine and sitagliptin, he added.
Intensive lowering of blood glucose should be accompanied by structured self-monitoring of blood glucose, especially in high-risk people with long disease duration, in an attempt to avoid hypoglycemia-related adverse effects such as cardiovascular disease and related death, Dr. Aschner advised.
"In view of the possible long-term benefits of intensive lowering of blood glucose and the superior efficacy of insulin to optimize glycemic control, strong arguments could be made to use insulin early when the dose is expected to be fairly low, with a reduced risk of hypoglycemia," he concluded.
This study was funded by Sanofi. Dr. Aschner has served on advisory boards for AstraZeneca, Eli Lilly & Co, GlaxoSmithKline, Janssen, Merck, Sharpe & Dohme, Novartis, and Sanofi and on speakers’ bureaus for AstraZeneca, Eli Lilly & Co, Merck, Sharpe & Dohme, Novartis, and Sanofi.