Sanofi Presents New Results for Insulin GLP-1 Combo Soliqua

In January, Sanofi won the battle to be first in the US market with a fixed-dose combination of insulin and glucagon-like peptide-1 (GLP-1) receptor agonist, and presentations at this weekend’s 77th Scientific Sessions of the American Diabetes Association (ADA) added to the evidence of the benefits of this novel therapy for type 2 diabetes (T2D).

New results gleaned from the LixiLan-O and LixiLan-L phase 3 clinical trials to show the injectible, sold as Soliqua, can help those with the highest glycated hemoglobin (A1C) levels gain control quickly, with less risk of hypoglycemia or weight gain—and, most critically, without having to first try insulin alone.

In an interview with The American Journal of Managed Care^®, Rachele Berria, MD, PhD, vice president and head of the Diabetes Medical Unit for Sanofi, summarized where diabetes therapy has been before the arrival of the fixed-dose insulin GLP-1 combinations (the other being Novo Nordisk’s Xultophy). Berria said with the arrival of GLP-1 class following the dipeptidyl peptidase 4 inhibitors, there was a risk of overpromising patients they would lose weight, and it’s important to be realistic about what therapies can do.

Still, today’s therapies are a step forward over using insulin alone, when the prospect of weight gain caused many patients to balk at intensifying therapy. “With that one injection,” Berria said, the patient can not only achieve better glycemic control, but also see a positive effect on body weight. The gastrointestinal side effects seen in a GLP-1 therapy are mitigated.

As far back as the Diabetes Control and Complications Trial (DCCT), researchers gained an understanding of the benefit of early intensification of therapy and better diabetes management, but in the real world it didn’t always happen, Berria said. “Letting them go and fall off track will, of course, lead to deleterious consequences,” she said.

The task is to avoid that clinical inertia, which lets patients try for another 3 months, or another 6 months to get their A1C lower, instead of being proactive to gain control. This is where a fixed-dose combination therapy like Soliqua can help, Berria said.

“You have the opportunity of titrating it slowly as you would with insulin,” she said. “This makes it easier for patients to intensify therapy.”

“The key is to know when it’s time to do more,” she said. Here, there’s a lot of education to do with clinicians.

Studies involving iGlarLixi (Soliqua) at this week’s ADA Scientific Sessions include:

• A study that found patients taking iGlarLixi, compared with insulin glargine alone, could see greater reductions in A1C and bring their levels below the ADA recommended 7%, regardless of the level at screening. Patients were divided into 3 groups: A1C ≤8%, 8% and 9%. After 30 weeks, those in the iGlarLixi group reduced their A1C —1.1%, –1.4% and –2.4%, respectively; compared with –0.5%, –0.1%, and –1.8% for insulin glargine.¹
• More patients taking iGlarLixi gained glycemic control at 12 weeks than those taking insulin glargine alone in a post-analysis led by Frias et al of patients who took part in the LixiLan-O and LixiLan-L trials. Patients taking the combination therapy took less time to get their A1C below 7% and less time to get their fasting plasma glucose of ≤130 mg/dL across both studies.²
• In a study of patients whose A1C remained uncontrolled even after taking 2 oral antidiabetic agents, iGlarLixi brought greater reductions and brought more patients below 7% A1C, without additional hypoglycemia or weight gain. The combination of iGlarLixi was more effective than insulin glargine or lixisenatide alone.³
• In a study of patients with A1C all at 9% of above, patients were randomized to take iGlarLixi, insulin glargine, or lixisenatide. Only the iGlarLixi group achieved a mean A1C <7.0%, and the combination therapy also mitigated weight gain. This suggests that moving directly to the combination therapy instead of starting with insulin only may be a good option for patients with higher A1C levels.⁴

References

1. Niemoeller E, Souhami E, Wu Y, Jensen KH. iGlarLixi reduces A1C to a greater extent than basal insulin therapy regardless of A1C levels at screening. Presented at the 77th Scientific Sessions of the American Diabetes Association, June 9-13, 2017, San Diego, California; abstract 1079-P.

2. Frias JP, Domingo MP, Meneghini LF, et al. Shorter time to glycemic control with fixed-ratio combination of insulin glargine and lixisenatide compared with insulin glargine treatment alone. Presented at the 77th Scientific Sessions of the American Diabetes Association, June 9-13, 2017, San Diego, California; abstract 1084-P.

3. Russell-Jones D, McCrimmon RJ, Barder TM, Baradez C, Baxter MA, Davies M. iGlarLixi fixed-ratio combination vs insulin glargine and lixisenatide in patients with T2DM treated previously with two oral antidiabetics: LixiLan-O subgroup analysis. Presented at the 77^th Scientific Sessions of the American Diabetes Association, June 9-13, 2017, San Diego, California; abstract 134-LB.

4. Davies M, Russell-Jones D, Barber TM, Baradez C, Baxter MA, McCrimmon RJ. iGlarLixi fixed-ratio combination in patients with HbA1C >9%: LixiLan-O subgroup analysis. Presented at the 77th Scientific Sessions of the American Diabetes Association, June 9-13, 2017, San Diego, California; abstract 137-LB.