How the world’s first weekly insulin shot could change diabetes treatment in India

“Novo Nordisk has championed the cause of insulin. Insulin was discovered around 100 years ago, before which patients had to restrict their calorie intake to manage blood glucose, which led to people getting sicker. It took nearly 40 years to move from insulin with a short life to one with a 12-hour life and then one that could be taken once a day. Now, another 20 years later, we have a drug that can be taken just once a week,” said Vikrant Shrotriya, managing director of Novo Nordisk India.

This innovation has reduced the number of shots from 365 a year to just 52, he added.

First, how does it work?

For long-lasting effects, two key modifications were made to human insulin to develop insulin icodec.

First, a fatty acid chain was added to increase its affinity to a protein in the blood called albumin. While a week’s dose of insulin is delivered under the skin, this bonding with albumin creates an inactive depot of the drug. This bond is reversible and the drug is slowly released into the bloodstream throughout the week.

Second, three amino acid substitutions were also made to lower the molecule’s affinity to insulin receptors. Even after the molecule gets out of the albumin bond, the reduced affinity for insulin receptor means that the drug gets used slowly. The reduced affinity does not reduce the potency of the drug in any way.

“The impact of this drug is similar to that of any other insulin. The advantage for the patients, however, is that it would reduce the number of shots they have to take. This is likely to improve compliance as well,” said Dr SV Madhu, professor of endocrinology at GTB Hospital, New Delhi.

“By introducing better diabetes management products, we want to bring down the HbA1c level (a measure of average blood glucose levels over the last three months) from 8.9 to 7 in India,” said Shrotriya.

How is icodec different from normal insulin?

It is an insulin analogue — a genetically engineered version of human insulin — that increases its life within the body.

Before the discovery of insulin in 1921, a childhood diabetes diagnosis was fatal. Physicians prescribed starvation treatment — low-calorie diets with periods of fasting. “Patients with T1D were often kept in hospital for weeks or months at a time, while their calorie intake and glucose excretion were meticulously recorded,” the BMJ recalled in its history of insulin.

Initially, the insulin given to these patients came from extracts of mashed-up pig and cow pancreas. It was only in the 1960s when structure of insulin was discovered, it could be manufactured. It became more widely available after recombinant technology — which can be used to alter the genetic code of a protein — was developed in the 1970s.

Now, most insulin is commercially manufactured and altered in various ways to increase the duration it stays in the body or improve the way it is absorbed. Insulin icodec is one such development.

While everyone with Type 1 diabetes needs insulin injections because their body does not produce the hormone, when it comes to the more common Type 2, many can be managed with oral pills. Yet, 25 to 30% of the people end up needing insulin eventually.

Who is the drug meant for?

The drug is meant for two categories of diabetics:

One, people with type 2 diabetes who have failed to achieve blood glucose control even with the highest doses of oral medicines.

“Those living with diabetes for eight to ten years, with pills being unable to control the blood glucose levels, need to take insulin injections to prevent further complications. Yet, most of them are unwilling to switch to the shots. Around 93% of people wish for diabetes control without the use of insulin, and there is a need to change this mindset. Initiating insulin early can prevent damage to the organs, nerve endings, and the eye,” said Dr SK Wangnoo, head of endocrinology at Indraprastha Apollo Hospital, New Delhi. Not only patients, he said, but even doctors demonstrate an inertia to start their patients on insulin treatments.

Dr Madhu added that once patients do not meet their blood glucose targets despite the maximum allowed dose and combination of oral medications, they should immediately be moved to insulin, initially at a lower dose alongside oral pills before transitioning completely to insulin.

Shrotriya added, “Currently, there are 6 million people on insulin in India, but this number should at least be double. Insulin is a drug that is never abused and is very effective for the treatment of diabetes, yet people stay away from it. We are hoping that the convenience of using this drug would mean more and more people who are recommended insulin start using it.”

Two, it can also be used as background insulin by Type 1 diabetics.

Those with type 1 diabetes need a long-acting dose known as the basal dose, along with shots around the meal times known as the bolus dose, based on how many calories they consume.

“People with type 2 diabetes would be the best fit for this drug. This is because people with Type 1 diabetes already need to take the three doses a day; a fourth dose doesn’t add too much burden. Plus, they typically see more fluctuations in their blood glucose levels and need to adjust their insulin doses accordingly. When I put out a survey two years ago, some women reached out to me and said that they needed to adjust the dose during menstruation. This type of flexibility is not possible with a weekly dose,” said Dr V Mohan.

What about side effects?

The most common side effect of the medicine is hypoglycemia — a condition where the blood glucose levels fall too much — that can affect one in ten people. Dr Wangnoo, however, assures that this is the same level as seen with other daily insulin shots.

Dr Madhu adds, “The reason people notice these episodes of hypoglycemia with insulin is that their blood glucose levels are controlled for the first time with it. Even pills can cause episodes of hypoglycaemia, but when the blood glucose levels are through the roof the question of hypoglycaemia does not arise.”

How much does it cost?

The drug will cost Rs 261 per week.

It will be available in two doses of pre-filled pens — a 700 unit/ ml costing Rs 2,611 and a 2,100 unit/ ml costing Rs 7,883. A patient usually needs around 70 units per week, which may need to be scaled up depending on their needs.

“The Rs 261 per week cost is cheaper than the current price of other insulin analogues, which can cost anywhere between Rs 345 and 453 a week. This drug will essentially cost around R50 a day,” said Shrotriya.

How does it work with GLP-1 drugs?

The drug can also be used with novel GLP-1 molecules, with the company in fact developing such a combination drug alongwith its own semaglutide.

While icodec lowers blood glucose levels, it becomes more effective in combination with GLP-1 drugs. This is because abdominal obesity, which is reduced with GLP-1 drugs, reduces a person’s insulin sensitivity. Meaning, they need more insulin to process the same amount of sugar. “When the insulin resistance caused by adiposity goes down, patients would require lower doses of insulin. A weekly insulin shot would mean the patients can take their GLP-1 and insulin at the same time, improving compliance,” said Dr Wangnoo.

How many people in India need it?

Currently, 101 million people are living with diabetes and 136 million with pre-diabetes.

While initially most of them would be managed with pills, after five years, say, 5% to 10% would need insulin shots. And, after 10 years, maybe 20% to 30%. Even if we consider that only 20% need it, the number would still stand at around 20 million. There would definitely be more use for the drug in Type 2 diabetics because of the convenience of taking one shot and cost similar to other products in the market,” said Dr V Mohan.