Daily jabs of insulin are a painful reality for many with diabetes. That may change if researchers who have successfully tested oral insulin in rats are able to replicate those results in humans.

Nearly 350 million people worldwide suffer from diabetes, and that number is predicted to grow to more than 500 million by 2030. While the more common form, type-2 diabetes, does not always need insulin treatment, nearly a quarter of all diabetes patients depend on insulin injections. Estimated annual sales of oral insulin could be as high as $17 billion.

The benefits of an insulin pill include more than just ease of taking the drug. A pill would mean patients can start taking insulin earlier in the disease's development, which could reduce some of diabetes' secondary complications like blindness and the impaired healing that leads to amputations.

The idea of oral insulin has been around since the 1930s, but the difficulties of making it have previously seemed too large to overcome. First, insulin is a protein—when it comes in contact with stomach enzymes, it is quickly destroyed. Second, if insulin can pass through the stomach safely, it is too big a molecule (about 30 times the size of aspirin) to be absorbed into the bloodstream, where it needs to be in order to regulate blood-sugar levels.

In spite of the difficulties, Sanyog Jain at India’s National Institute of Pharmaceutical Education and Research and his colleagues have been working on delivering insulin in the oral form for many years. Their first fully successful attempt came in 2012, when they developed a formulation that successfully controlled blood-sugar levels in rats. But the materials used were too expensive to consider commercializing the technology.

Now, in a paper published in the journal Biomacromolecules, they have found a cheaper and more reliable way of delivering insulin. They overcome the two main hurdles by first packing insulin into tiny sacs made of lipids (fats) and then attaching to it folic acid (vitamin B 9 ) to help improve its absorption into the bloodstream.

The lipids they use are cheap and have, in the past, been successfully employed to deliver other drugs. They help to protect insulin from being digested by stomach enzymes, which gets it to the small intestine. When the lipid-covered sacs enter the small intestine, special cells on its lining, called microfold cells, are attracted to the folic acid. The folic acid helps activate a transport mechanism that can let big molecules pass through into the blood. The amount of folic acid used in the formulation also appears to be in the safe region.

In rats, Jain’s formulation was as effective as injected insulin, although the relative amounts that entered the blood stream differed. However, it exceeded injected insulin in one key aspect: whereas the effects of an injection subside in 6 to 8 hours, Jain’s formulation helped control blood-sugar levels for more than 18 hours.

The most important part of the research comes after successful testing in animals—the formulation needs to be given to human volunteers. But, Jain said, “at a government institute like ours, we don’t have the sort of money needed for clinical trials.”

He may not have to wait for long, as big pharma companies have been searching for an insulin pill formulation for decades. Two of them, Danish pharma giant Novo Nordisk and Israeli upstart Oramed are in a race to come up with a solution. Google’s venture capital arm, Google Ventures, recently invested $10m in Rani Therapeutics with the hope it will help develop an oral insulin product. Indian firm Biocon also does oral insulin research, and it recently signed an agreement with pharma giant Bristol-Myers Squibb.

Oramed is ahead of Novo Nordisk, with its oral insulin product soon to enter phase-II clinical trials, which is the most advanced stage any oral insulin formulation has ever reached. Oramed chief scientist Miriam Kidron said of Jain’s research: “Most people have the same basic idea to develop an insulin pill, but it's the little differences that will determine ultimate success.”

While Kidron did not reveal Oramed’s formulation, she said, “we attempted liposomal delivery before, just like Jain’s work, but we weren’t successful.” She warned that translating success from rats to humans is very difficult. And she is right—most drugs have a high cull-rate at each stage of their development. Even so, research like Jain’s gives hope that an insulin pill may not remain a dream for long.

Biomacromolecules, 2013. DOI: 10.1021/bm401580k (About DOIs).

This article was originally published at The Conversation.