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EASD: Liraglutide Plus Insulin Does Not Add Weight

The addition of insulin to the treatment regimen of type 2 diabetes patients on liraglutide (Victoza) doesn’t wipe out previously seen weight loss, and insulin also appears to help these patients achieve glycemic control, researchers said.

Among patients who had not achieved glycemic control with liraglutide and metformin therapy, the addition of insulin detemir (Levemir) helped decrease A1c by an additional 0.5% after one year of therapy (P<0.0001), said Stephen Bain, MD, professor of medicine at Swansea University in Wales. 

Bain stated that, “The bottom-line message from this study is that it looks like the combination of a GLP-1 and insulin is efficacious, it appears to be safe, it induces low levels of hypoglycemia, and it is a way of maintaining weight loss. He said the low levels of hypoglycemia seen in his trial were surprising considering the weight loss obtained with the therapy and the A1c control achieved.

No patient in the study experienced a major hypoglycemic event, and minor hypoglycemia was seen in 0.228 episodes per year among patients on the combination of insulin, liraglutide, and metformin. Other trials using insulin treatments had minor hypoglycemic events in the 3% range, Bain noted.

In the year-long study, patients who received insulin were able to maintain a weight loss of about 3.5 kg first achieved with liraglutide and metformin dual therapy, while patients who were maintained on liraglutide and metformin lost about 5 kg. That difference was significant at P=0.04.

Bain said one of the fears of prescribing insulin is that patients will gain weight. For a population of type 2 diabetes patients, where being overweight is one of the hallmarks of the disease, the prospect of additional weight gain with insulin is worrisome for clinicians and patients, he said. But the study showed that this fear was not realized.

The researchers recruited 988 patients who were unable to achieve an HbA1c goal of 7% while on a sulfonylurea and metformin and who then underwent a 12-week run-in phase with liraglutide and metformin; 167 of the patients dropped out before completion of the run-in phase.

After 3 months, 498 patients were able to reach the target when liraglutide was added and the sulfonylurea was eliminated from the regimen. Those patients were followed through for 52 weeks.


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Of the remaining 323 patients with HbA1c greater than 7%, Bain and colleagues assigned 161 to continue on liraglutide and metformin, and assigned the remaining 162 patients to liraglutide, metformin, and insulin detemir.

After 52 weeks, the patients who had an HbA1c above the goal — an average of about 7.7% after the run in phase — had experienced an average increase in HbA1c of 0.01% while those on insulin had reduced HbA1c by 0.50%. The patients who had achieved HbA1c after the run-in phase were followed observationally and they achieved an average HbA1c that remained less than 7%.

At the end of the trial:

  • 21.5% of patients on liraglutide and metformin had achieved an HbA1c goal of less than 7%;
  • 51.9% of patients on those drugs plus insulin had reached the target; and
  • 72.7% of the group being followed maintained HbA1cof 7% or lower.

Michaela Diamant, MD, PhD, professor of diabetology and director of the Diabetes Center at VU University Medical Center in Amsterdam stated that, “This treatment regimen is not common practice now.” “I think doctors would like to delay treating patients with insulin as long as possible.” “This treatment is not now approved anywhere, but I think in five years — when we have more confidence and experience with GLP-1 agonists — we will find more patients in this situation.” She also suggested that GLP-1 drugs might be employed to reduce insulin dosing, but “further studies will have to be done to determine that.”

In Bain’s trial, the patients were in their mid-50s and about 55% were men; they had been diagnosed with diabetes for 6.6 to 8.5 years and their average HbA1c was greater than 8%, although the observation group had a mean A1c of 7.7%. The body mass index of the group was about 35 kg/m2; their mean blood pressures were about 135 mm Hg systolic and 80 mm Hg diastolic.

A predefined composite endpoint — in which patients lowered HbA1c to less than 7%, experienced no weight gain, and had no hypoglycemic events — was achieved by 38.8% of the observational group maintained on liraglutide and metformin, in 25.9% of the patients randomized to receive insulin, and in 16.8% of those randomized to continue on liraglutide and metformin (P=0.06).

Practice Pearls:
  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Explain that a study comparing the addition of insulin detemir to liraglutide and metformin in Type 2 diabetes patients with the drug therapy alone found a significant reduction in HbA1c among those receiving insulin.
  • Note that those taking insulin did not experience more episodes of hypoglycemia over the 52-week trial nor did they gain weight, but they did not lose as much weight as patients receiving liraglutide and metformin alone.

Bain S, et al “Adding insulin detemir (IDet) to liraglutide and metformin improves glycaemic control with sustained weight reduction and low hypoglycemia rate: 52 week results” EASD 2011; Abstract 73.