Sanofi’s Toujeo Improves Diabetes Control, Giving Patients More Time in Range
For diabetic patients, achieving a certain “time in range” is a more realistic glucose control strategy than striving for a particular daily target, according to researchers working with Sanofi who spoke during the 56th Annual Meeting of the European Association for the Study of Diabetes.
This conclusion is based on the realization that improved treatments are only one of several elements in improving diabetes patients’ glycemic control and quality of life. As one patient said during a video, “Managing diabetes is like playing the lottery with your own life.” New therapies and management strategies strive to improve the odds.
For people with Type I diabetes, bringing HbA1C levels to below 7% is the goal, but “globally, only one quarter of patients reach that goal,” according to Tadej Battelino, University Medical Centre-University Children’s Hospital, University of Ljubljana, Slovenia.
There often is wide variability in glucose levels throughout the day, and between days, which makes insulin dose adjustments challenging. The variability is caused by changes in patients’ diets and activity levels, differences in administration, and even the pharmacokinetics and pharmacodynamics of the insulin itself.
One way to achieve better control, therefore, is to focus on time in range. “This is a new method of thinking,” Battelino stressed. Initially, he advised selecting a glucose target range between 70 and 180 mg/dL (3.9 to 10 mmol/L) “to help people reach the target. You can have a more stringent target range later. It helps people realize that although they may not have achieved the target range this hour or this half of the day, they can still improve today. This makes sense to patients and is easily measured with continuous glucose monitoring.”
To take a time-in-range approach, patients need stable insulin levels, he noted. Toujeo® offers that.
“It has a flatter pharmacodynamics profile than the first-generation basal insulin analog, insulin glargine, with less increase in continuous glucose monitoring-based levels from 20 to 24 hours and reduced night-time hypoglycemia,” Battelino said.
When Toujeo was compared to insulin degludec (Tresuba®) in Type I diabetics in a clinical trial, researchers found 20% less fluctuation throughout the day.
Real-world evidence supports that. In a Spanish study of nearly 200 people, evenly divided between those taking Toujeo and those taking insulin degludec, researchers reported similar results for the two drugs during 24-hour monitoring. However, Battelino said at night, Toujeo has a more significant effect.
There were smoother mean glucose curves between midnight and 6 a.m. with Toujeo, and lower nocturnal glycemic excursions. With the 70 - 180mg/dL target range, patients taking Toujeo achieved 13% greater time in range. With a narrower 70 – 140mg/dL target range, patients taking Toujeo saw an 18% time-in-range improvement over insulin degludec.
“That’s real-life evidence,” Battelino said. “A prospective, randomized clinical trial is expected to be completed by the end of 2021.”
The emphasis on time-in-range is part of Sanofi’s strategy to shift its focus toward a more individualistic approach that “improves the standard of care, not just the standard of treatment,” Cyril Grandchamp-Desraux, Sanofi’s global head of diabetes franchise – General Medicines, said. “We believe individualistic care builds better outcomes, and that innovation goes beyond medicine.”
This shift is designed to help patients achieve balance between hypoglycemia and hyperglycemic events, and therefore to achieve time-in-range targets.
Of the more than 463 million people living with diabetes, nearly half have not reached their target blood sugar levels despite therapeutic advances.
“In some countries, 60% to 70% have not achieved their targets,” Grandchamp-Desraux said. “Someone is dying every seven seconds from diabetes complications. As a global epidemic, diabetes is growing faster than health providers can keep up. It threatens to overwhelm the system.”
Another partial solution is to shift away from premixed insulin.
As Martin Haluzik, M.D., deputy director, Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, noted, “Premixed insulin usually is prescribed for patients needing a simple insulin plan,” to control daily and mealtime blood sugar. The UK health system recommends premixed insulin for patients with Type II diabetes whose HbA1C (the measure of glucose attached to hemoglobin) is high – at or above 9% – and who take oral antidiabetic drugs. Premixed insulin combines neutral protamine Hagedorn (NPH) insulin (which reduces blood glucose levels one to two hours after administration) with a short-acting insulin.
“Unfortunately, in real life, it can be difficult to find success with premix,” Haluzik said. The challenge is in finding the right balance between glycemic control and the risks of weight gain and hypoglycemia.
For example, the UK Health Improvement Network study of the electronic health records of 974 diabetic patients with a baseline HbA1C of 11.3 who switched to premixed insulin showed poor control was achieved. “At 12 months, only 20% of the patients reached their goal (an HbA1C below 7.5%).” Results were only slightly better at 24 months.
When similar patients were switched to Suliqua® – a combination of both Gla-100 and lixisenatide – Haluzik said, “Seventy-four percent of patients with HbA1C above 9% lowered it to below 7%.” Nausea was reduced when compared to administering lixisenatide alone, and body weight also was reduced when compared to Gla-100 alone. A separate, network analysis study also showed a higher probability of success using Suliqua than premixed insulin.
As Sanofi advances its diabetes solutions, it is considering real-world evidence as well as clinical data.
“We think real-world evidence is very complementary to classical clinical research,” Alan Divanovic, M.D., global head of medical, diabetes – General Medicines, Sanofi, pointed out. “Real life reflects and illustrates the situations that we may not be able to create in a randomized, controlled trial and provides learnings on the pain points that explain why so many people’s diabetes isn’t properly controlled despite so much investment in new therapeutics, education, and technology. Real-world evidence brings very interesting insights into this space.”