Lantus solostar

RGECs were cultured in 96‐well plates for 24 h, followed by a pre‐incubation with PKC‐β specific inhibitor LY‐333531 (10 nmol/L; Axon Ligands, Groningen, the Netherlands), PKC agonist phorbol‐myristate‐acetate (PMA; 10 μmol/L; Sigma), PKA inhibitor H‐89 (10 μmol/L; Sigma) or PKA agonist 8‐bromo‐adenosine 3′,5′‐cyclic monophosphate (8‐Br‐cAMP; 100 μmol/L; Sigma) for 30 min. Then RGECs were treated with AGEs (200 μg/mL; Abcam), AGEs (200 μg/mL) + insulin (1 IU/mL, Lantus Solostar, Sanofi, Beijing, China) or AGEs (200 μg/mL) + rhGLP‐1 (1.0 mg/mL; Shanghai Benemae Pharmaceutical Corporation) for another 24 h according to a previously used method detect of reactive oxygen species (ROS) production16.
RGECs were seeded in 24‐well plates and pre‐incubated with PKC inhibitor LY‐333531, PKC agonist PMA, PKA inhibitor H‐89 or PKA agonist 8‐Br‐cAMP for 30 min, and then treated with AGEs (200 μg/mL), AGEs (200 μg/mL) + insulin or AGEs (200 μg/mL) + rhGLP‐1 for 24 h. Detection of NO production followed a previous study16.

After a 3-week screening period, during the run-in period, all patients received subcutaneous injection of FlexPen^® Ref-InsAsp-US at a concentration of 100 U/mL (Batch numbers: HZF7372; HZFA196; JZFC499; JZFC879; manufactured by Novo-Nordisk) at mealtime until randomization. In addition, all patients were shifted from their current basal insulin to Lantus SoloSTAR^® (insulin glargine injection, 100 U/mL, manufactured by Sanofi-Aventis) once daily at the start of the run-in period and continued till study completion. The doses of Ref-InsAsp-US and Lantus were titrated during the run-in period to ensure diabetes control. During the treatment period, all patients received one of the following treatments: MYL-1601D (Batch number: BM18002196) manufactured by Biocon from a manufacturing process or Ref-InsAsp-US taken at mealtime in a prefilled disposable pen with a 3-mL cartridge. Frequent adjustments of insulin dose were discouraged. Study treatment dose and titration instructions were given to the patient at the time of medication dispense, and all subsequent study visits were as per the recommended ADA 2019 standard-of-care specifics (the targets were prandial or post prandial). The 7-point self-monitoring of blood glucose (SMBG) diary was assessed, reviewed, and discussed at each visit to ensure the effectiveness and safety of glycemic control.

The study design and methods for the FPG GOAL study (ClinicalTrials.gov identifier NCT02545842) have been reported previously [23 (link), 24 (link)]. Briefly, FPG GOAL enrolled individuals with T2D and an HbA1c > 53 mmol/mol (> 7.0%) to ≤ 91 mmol/mol (≤ 10.5%) and FPG > 7 mmol/L despite receiving stable doses of 1–3 OADs for at least 3 months. Participants were randomly assigned (1:3:3) to one of three self-monitored FBG target groups: > 3.9 to ≤ 5.6 mmol/L, > 3.9 to ≤ 6.1 mmol/L, or > 3.9 to ≤ 7.0 mmol/L. Subcutaneous once-daily insulin glargine 100 U/mL (Lantus^® SoloSTAR^®, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany) was initiated at a dose of 0.2 U/kg and was titrated over the 24-week treatment period using a pre-defined titration algorithm.
The study was conducted in accordance with the principles stated in the Declaration of Helsinki and in line with the International Conference on Harmonization guidelines for good clinical practice. An institutional review board at each site approved the study, and all participants gave written informed consent.