Insulin glargine 300U/ml for people with type 1 diabetes has met primary endpoint in the InRange head-to-head study versus insulin degludec, according to findings presented today at the Advanced Technologies and Treatments of Diabetes (ATTD) conference.
Adults living with type 1 diabetes achieved comparable time in range at 12 weeks after switching from their previous long-acting basal insulin treatment to second-generation longer-acting basal insulin Toujeo® (insulin glargine 300 units/mL) or insulin degludec 100 units/mL in the first randomized controlled trial (RCT) using time in Range (TiR) as primary endpoint
The InRange RCT was designed to compare Insulin glargine 300U/ml and insulin degludec 100 Units/mL (iDeg) in terms of time in range (TiR). TiR is a metric to assess blood sugar control and is the proportion of time a person with diabetes spends within the target range, commonly between 70 and 180 mg/dL. The study met its primary endpoint with non- inferiority of Insulin glargine 300U/ml versus iDeg-100 demonstrated for % TIR at 12 weeks.
InRange is an example of the increasing relevance to use time in range and glycemic variability markers as main endpoints in clinical trials, to derive evidence and improve understanding of treatments. Professor Pratik Choudhary
The main secondary endpoint was also met as non-inferiority of Gla-300 versus IDeg-100 was demonstrated for glycaemic variability as measured by glucose total CV. The study did not show superior TiR with Insulin glargine 300U/ml versus iDeg. Rates and incidences of hypoglycemia were comparable between Insulin glargine 300U/ml and iDeg-100 across ADA-recommended hypoglycemia categories.
Safety and tolerability findings were similar with both treatments, and in line with their established safety profiles within this patient group.
InRange is the first worldwide multicentred RCT to compare the second generation basal insulins, Insulin glargine 300U/ml and iDeg in people living with type 1 diabetes using TiR as the primary endpoint.
Professor Pratik Choudhary, Hon Consultant is Diabetes, DRC, Leicester Diabetes Centre, Bloom University of Leicester, said: “These results provide valuable information for clinicians, showing how these second generation basal insulins compare in terms of clinically relevant outcomes such as time in range, glucose variability and hypoglycaemia. Both of these second generation insulins have independently shown their benefits over older basal insulins, and now these data show that they offer similar benefits in terms of hypoglycaemia and variability in people with type 1 diabetes. InRange is an example of the increasing relevance to use time in range and glycemic variability markers as main endpoints in clinical trials, to derive evidence and improve understanding of treatments.”
Time in range and glucose variability are now recognised by national and international guidelines from Advanced Technologies and Treatments for Diabetes (ATTD), the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD) and the Association of British Clinical Diabetologists (ABCD) as key metrics to support effective diabetes management.
Previous research has shown that decreasing TiR and increasing blood sugar variability can increase the risk of long-term complications in people living with diabetes, including heart and kidney disease, and eyesight problems.
Debbie Woods, Head of Medical, General Medicines, Sanofi UK and Ireland, said: “We are delighted about the results of InRange study, underlining the value of the second generation basal insulins in the treatment of people with type 1 diabetes. The InRange study is an example of the relevance of time in range and glycemic variability, by providing evidence and improving our understanding of treatment. This is the first worldwide head-to-head trial conducted by Sanofi, comparing two second generation basal insulins for the treatment of people with type 1 diabetes using time in range as a primary endpoint. This shows our commitment to continuously improving the management of diabetes, for healthcare professionals and people living with diabetes.”
About InRange (NCT04075513).
InRange was the first worldwide multicenter randomized controlled trial to compare Insulin glargine 300U/ml and iDeg in people living with type 1 diabetes using TiR as the primary endpoint. The study randomized 343 adults whose type 1 diabetes was insufficiently controlled (HbA1c ≥ 7% to ≤10%) at screening by multiple daily injections including another long-acting basal insulin. Previous rapid-acting insulin treatment was maintained. People were treated for 12 weeks, and blinded Continuous Glucose Monitoring (CGM) was used in Week 12 to measure their TiR (glucose ≥70 to ≤180 mg/dL) and other related metrics.
The study met its primary endpoint, demonstrating the non- inferiority of insulin glargine 300U/ml versus iDeg-100 for the percentage of TIR at Week 12 (52.74% with Insulin glargine 300U/ml vs 55.09% with iDeg; least squares [LS] mean difference: 3.16%; 95% confidence interval [CI]: 0.88 to 5.44; p=0.0067).
The study also met its first main secondary efficacy endpoint, with participants showing comparable glycemic variability, measured as the coefficient of variation at Week 12 (39.91 with Insulin glargine 300U/ml and 41.22 with iDeg; LS mean difference: -5.44; 95% CI: -6.50 to – 4.38; non-inferiority p<0.0001). The second main secondary endpoint of superiority for percentage of TiR for Insulin glargine 300U/ml with respect to insulin degludec 100U/mL was not demonstrated (LSM difference -2.35% (-4.75 to 0.05); p= 0.0548).
Other secondary descriptive endpoints included change in HbA1c values from baseline (8.29±0.82% with Insulin glargine 300U/ml and 8.34±0.80% with iDeg) to Week 12 (7.51 LS mean change from baseline: -0.75%; 95% CI: -0.87 to -0.64 with Insulin glargine 300U/ml; 7.38; LS mean change from baseline: -0.92%; 95% CI: -1.03 to -0.81 with iDeg; LS mean difference in change: 0.17; 95% CI: 0.01 to 0.32), showing an effective reduction of HbA1c from baseline to 12 weeks with both treatments.
Rates and incidences of hypoglycemia were comparable between Insulin glargine 300U/ml and iDeg across ADA-recommended hypoglycemia categories. Rates of any anytime hypoglycemia were 109.4 per patient-year (PPY) with Insulin glargine 300U/ml and 114.9 PPY with iDeg (rate ratio: 0.95; 95% CI 0.82 to 1.11), while rates of anytime severe hypoglycemia (ADA Level 3) were 0.2 PPY with Insulin glargine 300U/ml and 0.3 PPY with iDeg (rate ratio: 0.76; 95% CI: 0.45 to 1.28).
Safety and tolerability findings were similar with both treatments, and in line with their established safety profiles within this patient group. 50 participants using Insulin glargine 300U/ml experienced adverse events, 4 of which were considered to be related to treatment, while 35 participants using iDeg experienced adverse events, 7 of which were considered to be related to treatment.