Head to Head Comparison of Januvia and Victoza

The first head-to-head comparison across new incretin drug classes in Type 2 diabetes suggests that liraglutide (Victoza) outperforms sitagliptin (Januvia) for glucose control but additional questions remain….

Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, reduced A1c by an absolute 0.60% more at the 1.8 mg dose and 0.34% more at 1.2 mg than the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin (both P<0.0001), according to a new report in The Lancet.

This difference in the open-label, randomized trial passed non-inferiority criteria and met superiority on both counts.

The improvement would likely yield a clinically relevant advantage in microvascular complications and risk of diabetes-related mortality, they wrote.

Although potentially useful information for clinicians in choosing among the several incretin drugs now available, these results still don’t place liraglutide as the undisputed first-line agent after failure of metformin alone, cautioned an accompanying commentary.

Nearly all published randomized trials of incretin therapies have compared them with a placebo or a reference glucose-lowering agent, wrote André J. Scheen, MD of the University of Liège in Belgium.

One exception was the LEAD 6 trial, which reported superior achievement of A1c goals with liraglutide versus the GLP-1 inhibitor exenatide (Byetta).

Safety and comparative efficacy over the long term during the progressive decline in beta-cell function responsible for loss of glucose control remain open questions. Also, sitagliptin is a once-daily pill, which might be easier to administer than liraglutide as a once-daily injection, and is less expensive — both issues that may need to be taken into consideration on an individual basis, they noted.

“In our opinion, the range of Type 2 diabetes is so heterogeneous that treatment probably needs to be tailored to individuals rather than strictly standardized,” they concluded in their commentary.

Richard Bergenstal, MD, American Diabetes Association president for medicine and science agreed. “We’ve learned in the last several years and the last big trials that while A1c is critically important in preventing microvascular disease, you also have to look at weight gain, hypoglycemia, and quality of life…. We are back to more individualizing.”

Incretin therapies have to compete with other more commonly used and less expensive options for initial add-on therapy after metformin failure — a sulfonylurea, basal insulin, or thiazolidinedione, Bergenstal said.

The results suggest that liraglutide and sitagliptin would both be good options for patients when weight and hypoglycemia are an issue, and that liraglutide may be better for those who have farther to go to get to goal, he said.

Both drugs resulted in weight loss over 26 weeks, although participants lost more with the 1.8 and 1.2 mg liraglutide dosethan with sitagliptin (-3.38, -2.86, and -0.96 kg, respectively).

For the secondary composite endpoint of hemoglobin A1c of less than 7.0%, no hypoglycemia, and no weight gain, the same pattern was seen (46%, 37%, and 14%, respectively, P<0.0001 for both liraglutide groups versus sitagliptin).

The international trial included 665 patients ages 18 to 80 with Type 2 diabetes inadequately controlled on metformin as indicated by a A1c of 7.5 to 10.0%. Participants were randomized to once daily injections of liraglutide at 1.2 mg or 1.8 mg or oral sitagliptin once daily (100 mg).

After 26 weeks of treatment, results for the primary endpoint of hemoglobin A1c reduction compared with baseline were:

• –1.50% for 1.8 mg liraglutide (95% confidence interval –1.63 to –1.37)
• –1.24% for 1.2 mg liraglutide (95% CI –1.37 to –1.11)
• –0.90% for sitagliptin (95% CI –1.03 to –0.77)

More patients were able to get to goal on liraglutide as well.

Patients on 1.8 mg liraglutide were 4.50 times more likely (95% CI 2.90 to 6.97) and those on 1.2 mg liraglutide were 2.75 times more likely (95% CI 1.78 to 4.25) than those on sitagliptin to reach the target of a hemoglobin A1c under 7.0%. However, liraglutide was associated with more treatment-emergent adverse events, particularly GI events.

Nausea occurred in 27% of patients on 1.8 mg liraglutide and 21% on 1.2 mg liraglutide compared with 5% on sitagliptin. About 5% in each group reported minor hypoglycemia. There were no cases of pancreatitis.

Practice Pearls:

• Explain to interested patients that metformin is commonly the first treatment started in conjunction with exercise and lifestyle changes after diagnosis of Type 2 diabetes.
• Note that once metformin fails to achieve adequate glucose control, there are many treatment options.

Pratley RE, et al “Liraglutide versus sitagliptin for patients with Type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial” Lancet 2010; 375: 1447–56.

Scheen AJ, Radermecker RP “Addition of incretin therapy to metformin in Type 2 diabetes” Lancet 2010; 375: 1410–12.