For any diabetic patient, there could not be anything more Important than insulin. Patients with Type 1 diabetes cannot produce insulin and patients with Type 2 diabetes cannot produce enough insulin or make too much. The insulin hormone contributes to significant metabolic functions of the body, providing cells with needed energy. Based on the blood sugar levels and other hormones, pancreas is responsible for insulin production, which allows the cells in muscles, fat, and liver to absorb glucose. Diabetes is a life-threatening condition which happens when the body either does not produce enough insulin or no longer uses the insulin it produces effectively. For proper bodily functions, insulin play an important role in diabetes treatment and prevents complications associated with it. Type-1 diabetic patients need to inject insulin four to five times a day as glucose cannot enter the cells of muscles for energy without insulin. Type-1 diabetes often occur in children and its exact cause is unknown however genetic risk cannot be ignored. Type-2 diabetes, also known as adult-onset diabetes affects 85-90% of all people with diabetes. Lifestyle conditions, eating habits, stress, medical conditions, and genetics are some of the factors responsible for increased risk of type-2 diabetes. About 50% of type-2 diabetes population require insulin injection within 6-10 years of diagnosis if the condition is not managed at early stages.

Types of Insulin

Insulin can be classified into five different types depending on how long it takes to function in the body to control blood sugar levels. Since every individual is different, some people require more than one type of insulin.

·         Rapid-acting insulin

·         Short-acting insulin

·         Intermediate-acting insulin

·         Mixed insulin

·         Long-acting insulin

Rapid-acting Insulin

Often used at the start of a meal, rapid-acting insulin work over a narrow and more predictable range of time. The insulin starts working somewhere between 2.5 to 20 minutes after injection and can last up to five hours. The rapid-acting insulin works just like insulin released by pancreas and improves blood glucose levels after a meal.

Short-acting Insulin

Often used 30-60 minutes before a meal, short-acting insulin takes effect to wear off more quickly than long-acting insulins. Its effect starts to show up two to five hours after injection and lasts for a period of six to eight hours. The short-acting insulin are clear and do not settle if the bottle sits for a while.

Immediate-acting Insulin

Immediate-acting insulin, also known as background or basal insulins begin to work about 60-90 minutes after injection. Its maximum effect starts to show up 1-1.5 hours after injection and it lasts for 16-24 hours. These insulins contain added substances that make them work for a long time, which may make them look cloudy.

Mixed Insulin

The mixtures of insulin can be combined in a single syringe unit, but all insulins cannot be mixed. The insulin starts to work as quickly as the fastest-acting insulin in the combination and lasts as long as the longest-acting insulin in the mixtures. 

Long-acting Insulin

Long-acting insulin have no peak and can last for up to 24 hours. Its maximum effect can be observed after 3-4 hours.

According to TechSci research report on “Global Human Insulin Market By Indication (Type I Diabetes, Type II Diabetes), By Brand (Lantus, Humulin R, Novolin R, Humulin N, Exubera, Afrezza, Novolin N), By Route of Administration (Subcutaneous, Transdermal, Nasal, Intravenous, Oral and Others), By Type (Basal, Bolus, Pre-mixed, Biosimilar, Traditional), By Onset Time (Rapid acting, Short-acting, Intermediate acting, Long acting, Pre-Mixed, Inhaled, Ultra-long Acting), By Products (Insulin Pens, Insulin Pumps, Infusion System, Injections), By Region, Forecast & Opportunities, 2025”, Global human insulin market was valued at USD26.91 billion in 2019 is expected to grow at a steady CAGR of 8.01% during the forecast period. Growing geriatric population, increasing diabetic patients, rising prevalence of obesity, and increasing demand for human insulin analogs are contributing to the surging demand for human insulin market, globally. Now a days, diabetes is not only restricted to geriatric population, but it is also common among youth. Also, the technological advancements have eradicated human physical activities leading to obesity and diabetes disorders which is directly influencing the growth of the market. Cost effectiveness, reimbursement prices and strict regulatory requirements for approval of insulin can be considered as a major restraining factor for the market as everyone suffering from diabetes might not be able to afford insulin.

Biosynthesis of Human Insulin

Although diabetic patients are being treated with insulin, that was purified form of bovine or porcine pancreas since 1920s, the development in the field of genetic engineering allowed scientists to produce human insulin in laboratory with recombinant DNA technology. The technology requires the use of restriction enzymes, which cut DNA at specific sequences. Then the cut-out gene is inserted into a bacterial DNA known as plasmid, which is re-introduced into bacterial cells, creating many copies of the gene.

The recombinant human insulin is produced using either E. coli or Saccharomyces cerevisiae. By solubilization and refolding procedures, the insulin precursors (known as Preproinsulin) are produced as inclusion bodies and fully functional polypeptides. Removal of single peptide during insertion into the endoplasmic reticulum further creates proinsulin. Proinsulin consists of three domains, an amino-terminal B chain, a carboxy-terminal A chain and a C peptide. Within the endoplasmic reticulum, exposing proinsulin to specific endopeptidases, mature form of insulin is created. Then, insulin and free C peptide are packed in the Golgi into secretor granules accumulating in the cytoplasm.  Stimulating the beta cells appropriately, insulin is secreted from the cell through exocytosis, which later diffuses into islet capillary blood.

Generally, E. coli bacteria is preferred to produce recombinant proteins owing to its advantages such as easy to handle, simple media requirement, high growth rate, high yield and cost-effective. For commercial manufacturing of human insulin, Saccharomyces cerevisiae is the preferred yeast strain as they are amenable to various genetic manipulation and are easy to handle.

Different Ways to Administer Insulin

Insulin Injections

Most people administer insulin by drawing it up into a syringe and injecting it into the fat beneath the skin. Insulin must not be injected into the muscles otherwise body may absorb it too quickly, and it might not last as long. Injecting is a painful procedure, which also requires manual dexterity. People who inject insulin should rotate their injection sites as using the same spot can cause lumps or indentation, interfering with insulin absorption. Insulin can be injected in thighs, arms, buttocks, or abdomen.

Insulin Pens

Insulin pens are easier alternatives to administer insulin as they allow more simple, accurate and convenient delivery than using a needle and syringe. The pen makes the whole procedure of injecting insulin less intrusive and inconvenient. Most insulin pen fall into one of these two categories, disposable pen, and reusable pen. A disposable pen contains a prefilled insulin cartridge, and the entire unit can be thrown away after a single use. A reusable pen consists of an insulin cartridge, which can be installed after discarding the previous one. The insulin pen must be stored in the refrigerator but make sure to inject the hormone at room temperature only. Insulin pens should not be stored with an attached needle otherwise it can affect the cleanliness and sterility of the needle.

Insulin Pumps

Insulin pumps are compact and computerized devices that mimic the way human pancreas work. They deliver small dosages of short acting insulin continuously to deliver variable amount of insulin when a meal is eaten. Doctor sets the basal insulin rates, which can be programmed at one or multiple basal settings based upon the needs. Most insulin pumps come with built-in bolus calculators to evaluate the amount of insulin required at the mealtime based on the glucose levels. Basically, two types of pumps are available in the market such as traditional insulin pumps, and insulin patch pumps. Traditional insulin pumps consist of an insulin reservoir and pumping mechanism, attached to the body with tubing and infusion set. One can program insulin delivery for meals, specific types of basal rates or suspend insulin infusion in traditional insulin pumps. Whereas an Insulin patch pumps consists of a reservoir, pumping mechanism and infusion set within a small case. These can be controlled by a separate device that allows programming of insulin deliver for meals.

Jet Insulin Injectors

Jet insulin injectors are a perfect solution for people who find insulin injections unsettling in any way. The jet injector uses a high-pressure narrow jet of the injection liquid to penetrate the epidermis and disperse insulin into the subcutaneous adipose tissue compartments. Their speed makes jet injectors very efficient and pain-free.

Inhalable Insulin

Inhalable insulin is a concentrated powdered form of insulin that is delivered into the system with an inhaler. Inhaled insulin is more rapidly absorbed than injected insulin as it reaches the lungs with a faster peak concentration and inhibits more rapid metabolism. However, inhalable insulin was pulled off from the market due to increased risk of hypoglycaemia for patients who smoked.

Conclusion

Insulin has undergone multiple evolutions since the introduction of the first synthetic “human” insulin in 1921. Diabetes technology has improved dramatically with better pumps, more accurate CGMs and smart pens that record insulin dosing, etc. However, there is still no perfect insulin that perfectly mimics body’s physiologic production of the hormone, so the researchers need to seek better formulations that last longer and do not have peaks.

According to TechSci research report on “Asia Pacific Biosimilar Insulin Glargine & Lispro Market By End User (Type 1 Diabetes and Type 2 Diabetes), By Country (Japan, China, India, South Korea, Bangladesh, Pakistan), Competition, Forecast & Opportunities, 2024”, Biosimilar is a biological product which is similar to the reference product, already approved by authorities and marketed by companies other than the patent holder company. Insulin is a hormone produced by pancreatic cell which is responsible for absorption of glucose from the blood. Lack of insulin in the body causes diabetes. Insulin is available in different forms depending upon the sources such as animal derived, chemically synthesized or produced through recombinant technology. Insulin can be categorized as fast acting, immediate acting and long acting depending upon the absorption of insulin from the blood in the body. Glargine and lispro are two types of insulin.