Active ingredient: Insulin Glargine
Chemical name: 21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin
Chemical structural formula:
Molecular formula: C267H404N72O78S6
Molecular weight: 6063
Excipients: Zinc chloride, M-cresol, Glycerol, Sodium hydroxide (for pH adjustment), Hydrochloric acid (for pH adjustment), Water for injections.
In healthy subjects and diabetic patients, insulin serum concentrations indicated a slower and much more prolonged absorption and showed a lack of a peak after subcutaneous injection of insulin glargine in comparison to human NPH insulin. Concentrations were thus consistent with the time profile of the pharmacodynamic activity of insulin glargine. The graph below shows the activity profiles over time of insulin glargine and NPH insulin.
Insulin glargine injected once daily will reach steady state levels in 2-4 days after the first dose.
After subcutaneous injection in diabetic patients, insulin glargine is rapidly metabolized at the carboxyl terminus of the Beta chain to form two active metabolites M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). In plasma, the principal circulating compound is the metabolite M1. The exposure to M1 increases with the administered dose of Basalin. The pharmacokinetic and pharmacodynamic findings indicate that the effect of the subcutaneous injection with Basalin is principally based on exposure to M1. Insulin glargine and the metabolite M2 were not detectable in the vast majority of subjects and, when they were detectable their concentration was independent of the administered dose of Basalin.
In clinical studies, subgroup analyses based on age and gender did not indicate any difference in safety and efficacy in insulin glargine-treated patients compared to the entire study population.
The following content is intended to answer your questions only and is not intended to be used for promotional purposes or as a clinical medication guidance.
※Product Characteristics
● What is the basic information about Basalin®?
The generic name of Basalin® is insulin glargine injection. It contains insulin glargine as its active ingredient and is intended for people with diabetes who require insulin treatment. This medicine was approved for sale in China in 2005. Insulin glargine is a long-acting insulin that requires a single daily subcutaneous injection. The appropriate dose varies from patient to patient and should be adjusted based on target blood glucose levels. Notably, Basalin® is classified as a biosimilar, meaning it closely mirrors the quality, safety, and efficacy of the authorized reference (originator) product.
● Will Basalin® cause liver and kidney problems like some oral hypoglycemic drugs?
Basalin® is not associated with liver or kidney problems. The liver and kidneys are involved in the elimination of the body's own insulin. The introduction of exogenous insulin does not place an additional burden on these organs. In cases of liver or kidney dysfunction, the need for insulin may be reduced due to the reduced breakdown of endogenous insulin. Therefore, patients should continue to monitor their blood glucose levels while using insulin and adjust the dose if necessary.
● Is injecting Basalin® addictive? Will higher doses lead to dependence?
Basalin® is not associated with addiction or dependence. Drug addiction is defined as "the interaction of drugs with the body that leads to mental and physical abnormalities in the user, causing the user to develop an uncontrollable desire to acquire and continue to use" in order to experience the euphoria produced by these drugs, and is a form of psychological dependence. Insulin, on the other hand, is a hormone normally produced by the human body every day, which can help the body complete its metabolism and sustain life and is not itself an addictive substance. Whether you need to use insulin or not, and whether you can stop using it or not, depends on your blood glucose control and β cell function, and there is no addiction.
● Does Basalin® accumulate after 24 hours of action?
Basalin® achieves its long-acting mechanism by the gradual release of its active metabolite when administered under the skin in a neutral pH environment. Once the drug enters the bloodstream, its behavior and processing are very similar to that of human insulin. As a result, there is no build-up or accumulation. Studies have confirmed this lack of drug accumulation even during 12 days of continuous insulin administration in combination with glucagon (Heise et al, 2002).
● What are the precautions for the use of Basalin® in special populations? Are there efficacy and safety data?
Pregnant and breastfeeding women: Use with caution and under medical supervision. According to the foreign literature, there is no information on the use of insulin glargine during pregnancy in controlled clinical trials. The limited data on use during pregnancy from post-marketing surveillance indicate that insulin glargine does not adversely affect pregnancy or fetal or neonatal health, and no other relevant epidemiological information is available to date (as stated in the prescribing information).
Children: Use with caution. There is insufficient data on the use of Basalin® in children and its use in children should be under the supervision of a physician. The safety and effectiveness of insulin glargine in children have not been established in China due to limited experience (as stated in the prescribing information); the FDA has approved insulin glargine for use in children 6 years and older.
Older people: Use under medical supervision. The need for insulin may gradually decrease in the elderly due to progressive renal failure (as stated in the prescribing information).
※ Clinical Study
● What are the pharmacokinetics/pharmacodynamics (PK/PD) of Basalin®️ compared to the reference drug, the original insulin glargine?
A randomized, double-blind, triple-crossover study was conducted in a phase 1 clinical trial conducted jointly by Gan & Lee Pharmaceuticals and reported by Heise et al. at the American Diabetes Association (ADA) in 2021. The aim of the study was to assess the comparability of Basalin®️ with the original insulin reference product in terms of pharmacokinetics (PK), pharmacodynamics (PD) and safety. The reference insulin is approved in the United States and the European Union for the treatment of insulin-dependent diabetes mellitus.
The study involved 114 male participants with type 1 diabetes mellitus (T1DM). The results showed that Basalin®️ and the original reference drug had similar PK and PD profiles with comparable safety results.
The key PK parameters Cmax (maximum concentration) and AUC0-24h (area under the curve over 24 hours) were used as primary endpoints to evaluate the insulin metabolite M1. The study demonstrated PK bioequivalence between Basalin®️ and the reference drug, as evidenced by the 90% confidence intervals (CIs) falling entirely within the predefined PK similarity range of 80% to 125%.
Figure 1 Comparison of mean PK curves (±SEMs) and primary endpoints
The key pharmacodynamic (PD) measures, GIRmax and AUCGIR.0-24h, showed a comparable glucose infusion rate (GIR) pattern between Basalin®️ and the original reference drug. The PD endpoints met bioequivalence criteria with both the 90% and 95% confidence intervals (CIs) ranging from 80.00% to 120.00% similarity.
Figure 2 Comparison of mean PD curves (±SEMs) and primary endpoints
Consistent and comparable safety was observed across the three treatment groups, with all insulin types being well tolerated. The incidence of adverse events was similar and there were minimal cases of injection site reactions.
● What is the GLITTER study? What are the results of the studies?
The GLITTER studies, sponsored by Gan & Lee Pharmaceuticals, include two international, multicenter Phase 3 equivalence trials. These randomized, open-label studies were designed to evaluate the immunogenicity, efficacy, and safety of Basalin®️. In October 2023, Gan & Lee Pharmaceuticals presented data from these two clinical trials at the 59th European Association for the Study of Diabetes (EASD) Annual Meeting. The results of these studies showed that Basalin®️ is bioequivalent to the original reference drug in terms of immunogenicity, efficacy, and safety.
The primary endpoint of these studies is immunogenicity, which assessed by the proportion of patients developing treatment-induced anti-insulin antibodies (AIA) between treatment groups, defined as the development of a new confirmed positive AIA or a significant (at least fourfold) increase in titer from baseline to week 26. The secondary endpoint included efficacy, the change in glycosylated haemoglobin (HbA1c) from baseline at week 26, and safety, the incidence of all treatment-emergent adverse events (TEAEs) at week 26.
The GLITTER 1 study demonstrated immunogenicity bioequivalence between Basalin®️ and the original reference drug, as the percentage of subjects testing positive for treatment-induced AIA was similar and the 90% confidence interval (CI) (-5.4, 6.5) of the difference in proportions was well contained within the predefined similarity margins of -11.3 to 11.3. The key efficacy endpoint is similar, as the treatment difference in HbA1c was -0.08, with the 90% CI within the predefined equivalence limits (-0.4%, 0.4%). In addition, the safety profile was comparable, with similar rates of TEAEs in both groups.
Figure 3 Study design and resluts of GLITTER 1 study
The GLITTER 2 study also demonstrated immunogenicity bioequivalence as the proportions of subjects testing positive for treatment-induced AIA through week 26 were similar between Basalin®️ and the original reference drug, and the 90% CI of the difference in proportions was well within the predefined similarity ranges of -10.7 to 10.7. The key efficacy endpoint was similar as the treatment difference in HbA1c was 0.06, with the 90% CI within the predefined equivalence limits (-0.4%, 0.4%). In addition, the safety profile was comparable, with similar rates of TEAEs in both groups.
Figure 4 Study design and resluts of GLITTER 2 study
※ Clinical Application
● Does Basalin®️ require a higher dosage than the original insulin glargine to achieve equivalent efficacy?
There is no difference in the dosage of Basalin®️ compared to the original insulin glargine. A bioequivalence study conducted in Germany evaluated Basalin®️ and originator insulin glargine and showed no discernible differences in pharmacokinetic and pharmacodynamic characteristics between the two. This was confirmed by a 30-hour glucose clamp study in humans (Heise et al., 2021).
● If considering switching from insulin degludec to Basalin®, how should the dose be adjusted?
Basalin®️ can replace insulin degludec in equal doses 1:1. The results of two studies shed light on the comparison between insulin glargine and insulin degludec: In the BEGIN-ONCE China subgroup study, the mean daily dose of insulin glargine was similar to that of insulin degludec, with comparable glycaemic control (31 U). Similarly, the DEVOTE study demonstrated a parallel dosing regimen for insulin glargine and insulin degludec to achieve equivalent glycaemic control (31 U). However, in DEVOTE, insulin glargine was used at a slightly lower dose than insulin degludec while achieving similar glycaemic control.
● Can Basalin® be used in an insulin pump?
Basalin®️ cannot be used in insulin pumps.
● How to switch from using an insulin pump to using insulin glargine injection?
At the end of insulin pump therapy, the basal insulin dose in the pump can be directly converted to a 1:1 ratio for Basalin®.
● Is the physiological basal insulin level the upper dose limit for insulin glargine injections?
No, while basal insulins such as Basalin® aim to mimic the body's natural insulin secretion patterns, it's important to note that people with diabetes often have insulin resistance. As a result, the physiological range of basal insulin secretion (18-32 IU/d) cannot serve as an upper limit for exogenous insulin supplementation.
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