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MUNICH -- Switching from sitagliptin (Januvia, Janumet in combination with metformin) to liraglutide (Victoza) as an add-on to metformin in type 2 diabetes improved composite endpoints important to patients, researchers reported.

In prespecified analysis of composite secondary endpoints of the LIRA-SWITCH trial, the proportion of patients whose HbA1c dropped at least 1.0 percentage points with no weight gain at 26 weeks was 52.8% with the glucagon-like peptide-1 (GLP-1) analog liraglutide compared with 29.1% with the dipeptidyl peptidase-4 (DPP-4) drug sitagliptin, a 2.85-fold difference (P<0.0001).

The proportion who got to the 7.0% HbA1c goal with no weight gain at the same time point was 48.3% versus 24.2%, a 3.40-fold difference (P<0.0001),, of the Advanced Metabolic Care + Research Institute in Escondido, Calif., and colleagues reported here at the European Association for the Study of Diabetes meeting.

Sitagliptin had a similar benefit in that composite plus systolic blood pressure under control at less than 140 mm Hg (44.9% versus 19.2%, OR 3.88, P<0.0001).

"When sitagliptin is insufficient to control glycemia, switching to liraglutide provides a clinically-relevant treatment option while still allowing subjects to remain on dual therapy," Bailey concluded.

"The idea of composite outcomes may be a little bit novel to the regulatory bodies but to our patients and us I think it's very intuitive that patients not only want to get to goal but get there safely with the least amount of hypoglycemia and preferably no weight gain," he added.

Sitagliptin was associated with more confirmed cases of hypoglycemia (1.5% versus 0.0%), although not more severe or documented symptomatic cases.

Considering that risk in a post hoc analysis, reaching the glycemic target without weight gain or any confirmed hypoglycemia at 26 weeks was 3.40-fold more likely with liraglutide (48.3% versus 24.2%, P<0.0001). "Really this is the endpoint I think our patients would value the most," Bailey told attendees.

Liraglutide, though, had more treatment-emergent adverse events, including those leading to discontinuation, dominated by nausea, Bailey noted. It also had more cases of lipase increases (11% versus 1%), although no pancreatitis occurred, and pulse rate increases (2.57 bpm versus -0.11 on sitagliptin, P=0.0011).

The trial included 407 type 2 diabetes patients with HbA1c levels of 7.5% to 9.5% who had been on a stable sitagliptin and metformin regimen who were then randomized to double-blind, double-dummy treatment with liraglutide (1.8 mg/day) or continued sitagliptin (100 mg/day), both along with metformin.

The primary outcome of change in HbA1c and key secondary of weight change also favored switch to liraglutide, .

However, it was no surprise that composite endpoints including weight as a key component would favor liraglutide, commented session co-chair of the University of Copenhagen.

"When you're comparing a DPP-4 inhibitor and a GLP-1 analog, when you put body weight into a composite the analog is always going to win out because the inhibitors are generally weight-neutral," she told 番茄社区. "So they're loading their chances of seeing a nice effect."

That might be important to patients who need to lose weight and don't mind the injection, she said.

Given that only about half of patients reached goal even with the switch, the trial supported a fairly early switch between agents for patients not at goal, of St.-Josef Hospital, Ruhr-University Bochum in Germany and a co-chair of the session, said.

Bailey agreed. "People are failing once they are above their goals, 7 or 8," he said. "These are people that should be changed therapy and this documents the effect of -- instead of additional therapy as is the usual outcome -- this switching approach. ... There has been historically a target to reach and then there's a separate higher target to do things differently. I believe the targets should be much closer. If you're not reaching goals, you should switch."

Adding DPP-4 and GLP-1 drugs together hasn't shown much incremental difference in HbA1c control, Nauck noted, "speaking against additive effects." And it's certainly not enough to justify the cost, Bailey added.

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