Background: MYL-1501D is a long-acting human insulin analogue with amino acid sequence, strength, and formulation identical to the reference product (insulin glargine), although both are manufactured by distinct processes. 
Aims: The aims of the phase 3 INSTRIDE studies were to compare the safety and efficacy of MYL-1501D with the reference product insulin glargine in patients with type 1 diabetes (T1D) after 52 weeks of once-daily administration (INSTRIDE 1) and in patients with type 2 diabetes (T2D) after 24 weeks of once-daily administration (INSTRIDE 2). The primary objectives were to show noninferiority (0.4% margin) of MYL-1501D to insulin glargine when administered once daily in combination with prandial insulin (INSTRIDE 1) or when administered once daily in combination with oral antidiabetic drugs (OADs; INSTRIDE 2), as measured by change from baseline in HbA1c at week 24. The secondary endpoints in both studies included metabolic readouts (eg, fasting plasma glucose [FPG], insulin dose, self-monitored blood glucose) and safety parameters (eg, adverse events, hypoglycemia, and allergic reactions). 
Method: In the INSTRIDE 1 study, after a 6-week run-in period on the reference product, 558 patients with T1D (HbA1c ≤9.5%) were randomized to receive once daily MYL-1501D (n=280) or insulin glargine (n=278) in combination with thrice-daily mealtime insulin lispro for 52 weeks. The INSTRIDE 2 study enrolled 560 patients with T2D who were either insulin naive (HbA1c >7.5 to ≤10.5%; n=230) or had been on stable once-daily insulin glargine for at least 3 months before screening (HbA1c <10.5%; n=330). All patients were on stable doses of OADs for at least 3 months before screening. Patients were randomized to once-daily MYL-1501D (n=277) or insulin glargine (n=283) for 24 weeks and continued their OADs.
Results: MYL-1501D met the criteria for noninferiority to insulin glargine for change from baseline in HbA1c at week 24 in the intent-to-treat population in INSTRIDE 1 (least squares [LS] mean difference between treatment groups, 0.03; 95% confidence interval [CI]: -0.066, 0.117) and INSTRIDE 2 (LS mean difference, 0.06; 95% CI: -0.098, 0.218). Secondary efficacy measures, including change from baseline in FPG, were generally similar in the 2 treatment groups in both studies. There were comparable findings for both treatment groups for safety outcomes, including adverse events, hypoglycemia, allergic reactions, and weight change in INSTRIDE 1 and 2. Similar efficacy and safety profiles were also observed between the 2 treatment groups within the insulin-naive and insulin-treated subgroups in INSTRIDE 2. 
Discussion: Both MYL-1501D and insulin glargine, when used in combination with prandial insulin in patients with T1D (INSTRIDE 1) or with OADs in patients with T2D (INSTRIDE 2), were effective and had similar metabolic and safety profiles.

Efficacy and safety of proposed biosimilar MYL-1501D vs reference insulin glargine for T1D and T2D: the INSTRIDE studies