Taking an insulin is like letting a new partner into your life. You have to know everything about him/her. It is not a temporary phase. Doctors and nurses can’t tell you how to treat your partner. They can only give guidelines. How much you will fit in with your partner depends on you.

This may seem like a fairy tale. As if it is said by someone who doesn’t have diabetes and who doesn’t know how difficult it all is. Diabetes is a “lifelong” disease, but it is not untamable. There are medications that can fit into each and every life. In order to make it successful, the doctor needs to know – when to introduce insulin, which insulin, how many units to start with, how to change the types of insulin. It is also important that the person who takes insulin – understands everything and wants to find the right insulin with the right measure for his/her lifestyle.

In our country, in Serbia, it always starts with human insulin. Insulin is free. If a suitable solution cannot be found within 6 months – you can switch to another insulin. What does it mean? Human insulin did not meet the needs – it was not possible to achieve “normal” morning glycemia of 4 – 6 mmol/l, without nocturnal hypoglycemia. Or, normalization of postprandial glycemia was not achieved (i.e., 2 hours after a meal, glycemia was not 7.8 – 9 mmol/l). If HbA1c ≤7% could not be achieved during 6 months without nocturnal hypoglycemia, or due to persistent postprandial hyperglycemia, then you can switch to an insulin analogue – and then it becomes free in Serbia.

This picture was taken in 2017. Human insulins are placed in the first two rows. Then, boxes with insulin analogues are lined up. Today, after 2-3 years, there are 2 more insulin analogues on the Republic Fund Health Insurance list – Tresiba and Fiasp in a new insulin pen, Flextouch. Ryzodeg is also expected.

Why are that many insulins needed?

Because people are not identical. It is best felt by people with type 1 diabetes, who are completely dependent on insulin. They have certainly tried each new insulin and can describe exactly how it works for them. Many found the “latest” insulin unsuitable for them, so they returned to the “old” one – which they are used to and which is quite good.

People with type 2 diabetes can also feel the differences, although they are not completely dependent on insulin. In type 2 diabetes, in addition to progressive β cells weakness, there is resistance to insulin, a kidney that “does not filter sugar”, a stomach that works too fast, intestines that do not secrete intestinal hormones – GLP-1, a brain that does not recognize satiety. Insulin resistance is a complex concept. It can be at the level of the liver – which means that the liver constantly produces and releases sugar into the blood, especially at night. Also, it can be in muscles – which do not take glucose from the blood and do not use it for energy. Insulin resistance can be at the level of adipose tissue – which constantly releases free fatty acids, which destroy pancreatic β cells and stimulate the synthesis of cholesterol and triglycerides in the liver.

What does all this mean? Insulin in type 2 diabetes is needed to “break” the liver and provide normal morning blood sugar level, when metformin tablets fail. It is also needed to overcome high blood sugar after a meal, when the “exhausted” β cell fails. Other disorders in type 2 diabetes are solved by other medications. That is why it is pure art to find an adequate combination of insulin and medications in type 2 diabetes.

What is different in “basal” insulins?

Human basal insulins act unevenly and shorter. It takes them 2 hours to reach maximum effect. This effect lasts for about 10 hours and then slowly decreases. And during the “maximum” effect, it is not even. Then hypoglycemia is possible. The effect of HM basal insulin is 14-16 hours. Everyone wants basal insulin that works for 24 hours and that works evenly.

This is where the “basal” insulin analogues appear. Each of them are equally effective in achieving the target HbA1c, with constant titration. They differ in the way they achieve prolonged action, in the length of action, as well as in the stability of action. They also differ in the risk of hypoglycemia, weight gain and cardiovascular effects. Lantus works for 24 hours, Toujeo for 36 hours, Levemir for up to 24 hours, and Tresiba for up to 42 hours. Levemir causes the least weight gain. Hypoglycemia is the rarest in the titration period on Toujeo insulin, and afterwards there is no difference in relation to Tresiba. Tresiba shows the “calmest” effect. Insulins that have a calmer effect can be more easily titrated. The dose of some basal analogues (Levemir, Lantus) can be changed each evening, and some (Toujeo, Tresiba) only on the 5th day.

What is obtained by switching from one analogue to another?

Example: A person with type 1 diabetes is on Levemir insulin. He/she takes 40 units. Morning glycemia is between 5 and 9 mmol/l. If it is increased to 42 units – sometimes it is just right, but sometimes a hypo occurs. It seems that Levemir does not always work evenly. He/she was suggested to switch to Tresiba insulin. What will be gained by that? Stability and flexibility. That sounds a bit contradictory – but it’s true. Tresiba works for 42 hours – but there is no overlapping effect – and it sounds the opposite too. But it is true. Long-lasting effect gives flexibility in receiving insulin. It can be taken at any time in the morning, from 6 a.m. to noon. Or in the afternoon until evening, for example from 5 p.m. to 11 p.m. But a period between two injections must not be shorter than 8 hours – otherwise an overlap occurs.

Tresiba works fantastically evenly. If a person tries to adjust the dose so that he starts the day with glycemia of 4-5 mmol/l, without nocturnal hypoglycemia, then a lot is obtained in quality of life. Titration is performed based on the average of 2 morning glycemia on the 6th and 7th day, from the day of dose change. Many do not have patience to wait 5 days and prefer insulins whose dose can be changed on a daily basis.

What is obtained by switching from Toujeo to Tresiba insulin?

Honestly, everything is individual. Someone will notice less hypo, in the long run, on Tresiba insulin. Someone will notice that he/she needs fewer units of insulin. And someone will say that it doesn’t suit him “because it is so slow”. This is most often noticed by women with PMS. They cannot determine the exact day when the dose of Tresiba should be increased in order to cover the inconvenient PMS. With Toujeo insulin, they were achieving that more easily.

If HbA1c is around 9% – switching from Toujeo insulin to Tresiba will not fix anything.

Will there be a better “basal” insulin?

Yes – very soon! There will be basal insulins which will be given once in 7 days.

When a patient on basal bolus insulin therapy brings readings from a glucose-meter, or a notebook with over 100 measurements, – where to start from?

Start with the analysis of glycemia on waking up.

Many patients measure their glycemia for the first time before breakfast. This does not give a true picture of the effect of basal analogue! To adjust the dose of Tresiba insulin, an average of 2 morning glycemia should be found, five days after the last dose change. For Toujeo insulin, an average of 3 morning glycemia is required, also 5 days after the dose change.

The next thing to consider is whether there was hypoglycemia – at night or during the day. Only when the right dose of basal analogue is reached, the effects of bolus insulin can be analyzed.

What is the difference in bolus insulins?

Human bolus insulin starts to “work” after 30 minutes, acts for a maximum of 4 hours, and then its effect decreases. The problem with HM boluses is that they don’t start working so fast. When they “work to the maximum,” they don’t work as efficiently. If a dose is achieved to “work efficiently”, hypo is certain due to prolonged action.

Bolus analogues have a “more natural” effect. They failed to fully imitate the natural response of insulin to food, thus attention is needed. They include insulin lispro (Humalog), insulin aspart (NovoRapid) and glulisine (Apidra). They act significantly shorter and cause less hypoglycemia. They reduce the need for snacks. They can be administered just before a meal. Doses are easier to calculate in relation to carbohydrate (“sugar”) units in a meal and the corrections. However, they do not manage to overcome the postprandial jump in glycemia fast enough.

There is also an ultra-fast bolus analogue – FiAsp. It appears in the blood in 2.5 minutes. Insulin activity in the first 30 minutes is increased by 74%. It enables twice as much suppression of endogenous glucose production in the first 30 minutes, compared to insulin aspart. FiAsp has been shown to work great in T1DM. It starts acting fast and ending fast as well. And it perfectly overcomes postprandial glycemia in T1. It can be administered up to 20 minutes after starting a meal. If a meal is bigger, and especially if it lasts longer – it is necessary to divide the dose into two. In T2DM, people who were on FiAsp had less hypoglycemia, compared to those who were on insulin aspart. This did not affect HbA1c.

How to check the adequacy of bolus insulin?

There are 2 ways. One is to measure the blood sugar level, 2 hours after the end of a meal. Glycemia should not exceed 10 mmol/l.

Another way is to measure glycemia before the next meal, with a logical thinking that if the bolus insulin managed to “pick up” all the sugar after a meal, the glycemia before the next meal should be around 5-7 mmol/l. Measurements should be tried in both ways.