Study shows more people on Soliqua® had improved blood sugar control without weight gain and without low blood sugar events (hypoglycaemia) in first head-to-head comparison with premixed insulin

These findings come just ahead of Soliqua’s® launch in South Africa towards the end of July.

Johannesburg, 30 June, 2021 A new study of Soliqua® (a fixed-ratio combination of insulin glargine and short-acting glucagon-like peptide-1 receptor agonist – lixisenatide) has demonstrated both non-inferiority and statistical superiority compared to premix insulin (biphasic insulin-containing 30% insulin aspart + 70% insulin aspart protamine,  BIAsp 30) in terms of HbA1c reduction, as well as statistical superiority in bodyweight change in adults living with type 2 diabetes uncontrolled on insulin and oral anti-diabetic medicines.1 These findings come just ahead of Soliqua’s® launch in South Africa towards the end of July.

“Concerns about hypoglycaemia and weight gain are known barriers to adherence to treatment, especially insulin therapy with complex regimens. These results show better glucose control with iGlarLixi over BIAsp 30, as well as less bodyweight gain and less hypoglycaemia. They provide a robust level of evidence to support clinical decisions when basal insulin therapy needs to be advanced in people with uncontrolled type 2 diabetes, and may inform future treatment guidelines,” said  Kiolan Naidoo, Medical Advisor: Diabetes, for Sanofi South Africa.

 

A secondary analysis also found that study participants using Soliqua® reported greater improvements in patient-reported outcomes compared to premixed insulin, as measured by Treatment-Related Impact Measure Diabetes (TRIM-D) and patient- and physician-rated Global Treatment Effectiveness Evaluation (GTEE) scores.2 These tools include measurements of treatment burden, daily life, diabetes management, compliance, psychological health, and treatment effectiveness.

 

Dr Beki Magazi,  Medical Head of General Medicines at Sanofi South Africa, said “that while premixed is used by around 40% of people taking insulin globally to manage their type 2 diabetes today, recent real-world evidence suggests only 18.2% of people using it reach their blood sugar goal.3,4 Having Soliqua® available in South Africa provides a new, once-daily therapeutic option to help patients with type 2 diabetes reach their treatment goals”. Amongst adults, South Africa has a prevalence of diabetes of over 12%,5 and 90% of all people with diabetes have type 2 diabetes. While the prevalence rate of diabetes in South Africa is high, it is important to take into account that many people with diabetes are undiagnosed and some ethnic groups, such as the South African Indian population, are even more prone to developing the disease.6 This innovative treatment option from Sanofi will help millions of people around the world who live with inadequately controlled diabetes, continues Dr Magazi.

 

Soliqua® provides a suitable treatment option for patients uncontrolled on oral anti-diabetic drugs with a high HbA1c (above 9%) or those uncontrolled on basal insulin. These are patient groups of particular importance in South Africa, as data indicates that  67% of patients are uncontrolled with HbA1c levels above target, leaving them at increased risk of micro and macrovascular complications.7 Additionally, patients requiring treatment intensification beyond basal insulin will often require more complex treatment regimens. Increasing treatment complexity may lead to increased hypoglycaemia and weight gain as well as reduced adherence. Soliqua thus meets the need for effective therapeutic simplification in this population.7 Soliqua® is indicated for the treatment of adults with type 2 diabetes mellitus to improve glycaemic control when oral glucose-lowering medicines alone or combined with basal insulin do not provide adequate glycaemic control.   Soliqua® will be delivered in two pre-filled SoloSTAR® pens, providing different dosing options that may help answer individual patient insulin needs. The differentiation between pen strengths is based on the dose range and ratios of each pen. The SoloSTAR 50/100 pre‑filled pen contains 0.5 µg lixisenatide and 1 unit of insulin glargine. The SoloSTAR  33/100 pre‑filled pen contains 0.33 µg lixisenatide and 1 unit of insulin glargine.8

 

About the SoliMix study

The SoliMix study was a 26-week, open-label, multicenter, randomized controlled trial of 887 adults living with type 2 diabetes who were uncontrolled on a basal insulin plus metformin with or without a sodium-glucose cotransporter-2 inhibitor (SGLT-2i). The study compared the efficacy and safety of Soliqua® compared to a commonly used premixed insulin (BIAsp 30). Participants were randomized to switch from their prior insulin to either Soliqua® once daily or premixed insulin twice daily, with starting doses determined and adjusted weekly. Any metformin or SGLT-2i treatment was maintained through the study period. The study met its two primary endpoints and all three of its key secondary endpoints.

SoliMix data summary
Soliqua (n = 443) Premixed Insulin (n = 444)
HbA1c, % Baseline 8.61 ± 0.67 8.57 ± 0.65
LS mean change from baseline to Week 26 ± SE -1.30 ± 0.06 -1.05 ± 0.06
LS mean difference (97.5% CI)*   p-value for non-inferiority†   LS mean difference (95% CI)‡   p-value for superiority§ -0.24 (-0.41, -0.08)   p < 0.001   -0.24 (-0.39, -0.10)   p < 0.001
HbA1c, mmol/mol Baseline 70.6 ± 7.3 70.2 ± 7.1
LS mean change from baseline to Week 26 ± SE -14.2 ± 0.7 -11.5 ± 0.7
LS mean difference (97.5% CI)*   p-value for non-inferiority†   LS mean difference (95% CI)‡   p-value for superiority§ -2.6 (-4.5, -0.9)   p < 0.001   -2.6 (-4.3, -1.1)   p < 0.001
Bodyweight, kg Baseline 80.7 ± 16.5 82.2 ± 18.5
LS mean change from baseline to Week 26 ± SE -0.70 ± 0.20 +1.15 ± 0.20
LS mean difference (95% CI)   p-value for superiority* -1.86 (-2.28, -1.43)   p < 0.001
HbA1c < 7% without weight gain, n (%)   Odds ratio (95% CI)‡ 122 (27.5) 55 (12.4)
2.83 (1.98, 4.04); p < 0.001
HbA1c < 7% without weight gain and without hypoglycemia (plasma glucose < 70 mg/dL [< 3.9 mmol/L]), n (%)   Odds ratio (95% CI)‡ 86 (19.4) 31 (7.0)
    3.40 (2.19, 5.28); p < 0.001
HbA1c < 7%, n (%)§   Odds ratio (95% CI) 187 (42.2) 141 (31.8)
1.65 (1.25, 2.19)
Incidence and rates of hypoglycemia (safety population) n = 442 223.15 PY n = 441 217.85 PY
Level 1 (ADA definition: < 70 mg/dL [< 3.9 mmol/L] and ≥ 54 mg/dL [≥ 3.0 mmol/L])
n (%)   Odds ratio (95% CI)   PPY (events)   Rate ratio (95% CI) 114 (25.8) 170 (38.5)
  0.55 (0.42, 0.74)
2.03 (453) 2.83 (616)
  0.71 (0.52, 0.99)
Level 2 (ADA definition: < 54 mg/dL [< 3.0 mmol/L])
n (%)   Odds ratio (95% CI)   PPY (events)   Rate ratio (95% CI) 28 (6.3) 57 (12.9)
  0.45 (0.28, 0.73)
0.25 (56) 0.56 (121)
  0.40 (0.23, 0.71)
Level 3 (ADA definition: severe hypoglycemia)
n (%)   Odds ratio (95% CI)   PPY (events)   Rate ratio (95% CI) 1 (0.2) 2 (0.5)
  0.50 (0.04, 5.56)
0 (1) 0.01 (2)
  0.49 (0.04, 5.40)
Data shown are mean ± SD unless otherwise specified. *Primary endpoint was assessed at 0.025 for non-inferiority on HbA1c change from baseline then 0.05 for other endpoints, as the alpha was distributed to subsequent tests. †Two primary efficacy endpoints, non-inferiority of HbA1c reduction assessed using a margin of 0.3%; ‡Secondary endpoint was assessed at the alpha 0.05 level. §Secondary endpoint. A hypoglycemic event with severe cognitive impairment (hypoglycemic unconsciousness) requiring external assistance for recovery.   ADA – American Diabetes Association; AE – adverse event; BiAsp – biphasic aspart insulin; BMI – body mass index; CI – confidence interval; iGlarLixi – a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist, lixisenatide; ITT – intent to treat population; LS – least squares; PPY – per participant-year; PY – participant-year; SD – standard deviation; SE – standard error; T2D – type 2 diabetes

In a secondary analysis, participants using Soliqua® also reported greater improvements in patient-reported outcomes as measured by TRIM-D and patient- and physician-rated GTEE scores at 26 weeks.

  • TRIM-D results demonstrated greater improvements for participants using Soliqua® compared to those using premixed insulin, across domains including compliance, diabetes management, and psychological health, among others.3
  • GTEE findings showed that nearly twice as many patients reported complete control of their diabetes with Soliqua® compared to premixed insulin (27.5% vs 15%). Similarly, nearly twice as many physicians also reported treatment effectiveness (i.e., complete control of diabetes) with Soliqua® compared to premixed insulin (29.9% vs 15.3%).3

Safety findings were in line with the established profiles of both treatments. The most commonly reported adverse events in the study were hypoglycemia (31.2% Soliqua®, 42.4% premixed insulin), nausea (7.7% Soliqua®, 0% premixed insulin), headache (2.5% Soliqua®, 0.5% premixed insulin), dizziness (1.4% Soliqua®, 0.5% premixed insulin), and vomiting (1.1% Soliqua®, 0.2% premixed insulin).

 

About Sanofi Diabetes & Cardiovascular

Diabetes and cardiovascular disease affect millions of people worldwide, with many managing the complex challenges of both. Building on our portfolio evolution, heritage and expertise, Sanofi has a focused business unit dedicated to delivering innovative, value-based medicines and integrated solutions in these therapeutic areas. We are committed to a collaborative approach that involves strategic alliances with professional and patient associations, research institutions and leaders in healthcare and other industries, with the goal of advancing scientific knowledge, driving the convergence of science and technology, helping to improve outcomes and inspiring an evolution in care.  

About Sanofi

Sanofi, a global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi is organised into five global business units: Diabetes and Cardiovascular, General Medicines and Emerging Markets, Sanofi Genzyme, Sanofi Pasteur and Consumer Healthcare. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

 

References

1 Rosenstock J, Emral R, Sauque-Reyna L, et al. Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes: Clinical outcomes with iGlarLixi versus premix BIAsp 30 in the SoliMix randomized controlled trial. Diabetes Care. 2021 Jun 28;dc210393.

2 Polonsky W, et al. Improved treatment perceptions with iGlarLixi vs premix Insulin in type 2 diabetes (T2D) uncontrolled on basal insulin (BI) + oral antihyperglycemic drugs (OADs): patient-reported outcomes (PROs) of the SoliMix Trial, Presentation 747-P, American Diabetes Association (ADA) 81st Scientific Sessions (virtual event), June 28, 2021.

3 Market sales data, IQVIA

4 Jude E, Trescoli C, Emral R, et al. Effectiveness of premix insulin in type 2 diabetes: a retrospective UK cohort study. Diabetes Obes Metab. 2021;23(4):929-37.

5 International Diabetes Federation. IDF Diabetes Atlas, 9th edition. Brussels, Belgium; 2019. Available from: https://www.diabetesatlas.org. Accessed 18 June 2021.

6 Cardiovascular Diabetes Education. What is Type 2 diabetes and why does it occur? Available from: cdediabetes.co.za/home/diabetes/type-2-diabetes.html. Accessed 18 June 2021.

7 Kaplan H Amod A, Chadli A, et al. IDMPS Wave 7 Africa. Journal of Endocrinology, Metabolism and Diabetes of South Africa. April 19, 2021. https://doi.org/10.1080/16089677.2021.1897230.

8 Suliqua™ EU summary of product characteristics, 2017.