IDiabetes is one of the largest global health emergencies of this century. According to the International Diabetes Federation database published in April 2025, about 90 million people in the range of 20 to 79 years in India are diabetic, ranking second in the world after China. Diabetes is the shorter version of its full name, ‘diabetes mellitus’. Diabetes originates from the Greek word diabetes, meaning “a siphon” or “to pass through,” referring to excessive urination. Mellitus comes from the Latin word mellitus, meaning “honey-sweet,” referring to the sweet taste of urine due to sugar.
Remarkably, the symptoms of diabetes were described as early as 3,500 years ago in an ancient Egyptian papyrus. Although the exact location of the tomb remains unknown, the Papyrus was found between the legs of a mummy in the Assissif district of the Theban necropolis or city of the dead. The papyrus was 30 cm wide, 20.23 m long and consisted of 110 pages. It is widely regarded as the oldest surviving medical manuscript, written in hieratic script around 1552 BC. It contains chapters on ophthalmology, gynaecology, obstetrics, dentistry, surgery, etc. Georg Ebers, a well-respected Egyptologist, published a facsimile in Latin and English in 1875, after which it became known as the Ebers Papyrus. Around 100 AD, Aretaeus of Cappadocia provided what is considered as the first accurate clinical description of diabetes.
He wrote: “Diabetes is a wonderful affliction, not very frequent among men, being a melting down of flesh and limbs into urine. The patients never stop making water, but the flow is incessant, as if the opening of aqueducts”. He further observed that patients were unable to restrain either their thirst or urination; when deprived of water, their mouths became parched and their bodies dried, accompanied by nausea, restlessness, and intense thirst, ultimately leading to death. Over the past two millennia, scientific understanding of diabetes has advanced dramatically.
Today, the causes of diabetes and methods for its management are well established. Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin that it produces. In 1889, Joseph von Mering and Oskar Minkowski discovered the role of the pancreas in diabetes. They found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards. Later, in 1910, Sir Edward Albert Sharpey-Schafer identified insulin deficiency as the underlying cause of diabetes and coined the term insulin, derived from the Latin insula (meaning “island”), referring to the insulin-producing islets of the pancreas. The two most common types of diabetes are Type 1 and Type 2.
In Type 1 diabetes, the immune system destroys the pancreatic cells responsible for insulin production. Type 1 is still incurable; as a result, they are dependent on external insulin from a very young age. Type 2 diabetes is more common, which constitutes 90 per cent of all cases of diabetes. In India, there are an estimated 77 million people above the age of 18 years who are suffering from diabetes (type 2), and nearly 25 million are prediabetics, placing them at a higher risk of developing the disease in the near future. Type 2 diabetes can often be managed through lifestyle changes, including a balanced diet with controlled carbohydrate intake, regular physical exercise, reducing sedentary behaviour, adequate sleep, etc.
When lifestyle changes are not sufficient to control blood sugar levels, oral medication is prescribed. When oral medication fails to achieve adequate blood glucose control, injectable therapies – either GLP-1 (non-insulin) or insulin – are introduced into the body to control blood sugar levels and prevent further complications. Insulin is quite affordable and widely used in India. For many people with diabetes, managing their blood sugar levels requires daily insulin shots. Insulin shots are usually taken around mealtimes. Taking the shots sometimes requires privacy, particularly when the patient is at a party or in a public place.
However, using the insulin pump does not require taking injections at mealtimes. Insulin pumps offer a viable alternative. It is a small device, worn all the time on the body, that delivers insulin throughout the day and night via a tiny tube (cannula) inserted under the skin. The pump is programmed to deliver tiny amounts of insulin over 24 hours, depending on the insulin the patient needs. However, delivering insulin by shots is more common. In a study published in the journal Nature on 19 November 2025, scientists reported progress in developing a skin-applied gel capable of delivering insulin without injections.
The gel was initially tested on diabetic mice and pigs, and it was found that blood sugar levels were normalised within one to two hours of application and remained in the normal range for approximately 12 hours. Delivering insulin through human skin presents significant challenges. The outermost layer of the human skin, known as the stratum corneum, is only about 10 to 15 micrometres (10-6 m) thick, thinner than even a strand of human hair. But dead cells and fats form a protective layer that is tough to penetrate. While some small molecules can penetrate this layer, larger proteins, like insulin, typically cannot.
To overcome this obstacle, researchers developed a pHresponsive polymer known as OP, capable of penetrating the stratum corneum. The skin surface is mildly acidic, with a pH of around 5, while deeper layers of the skin are closer to a neutral pH of 7. pH is the potential of hydrogen; a pH of 7 is neutral (pure water), values below 7 are called acidic, while values above 7 are alkaline. At the acidic surface, the OP polymer becomes positively charged, allowing it to stick to the fatty acids within the skin, much like the attraction of opposite magnetic poles. As the pH gradually increases in deeper layers, the OP polymer changes to a neutral state that enables it to diffuse through fats in the skin.
The insulin-laden OP then efficiently migrates through the skin to dermal lymphatic vessels and systemic circulation, which would not normally be possible on its own. Laboratory studies have demonstrated that OP penetrates all layers of mouse and pig skin. In the case of a diabetic mouse, applying the gel once lowers the blood glucose level to a normal range within about an hour and keeps it within that range for roughly 12 hours. However, to achieve this, a very high OP-insulin of 116 units per kilogram (U/kg) of body weight, far beyond a typical human dose of insulin, is required. This could raise a concern that the insulin delivery through the skin might not be efficient enough.
In the case of diabetic miniature pigs, whose skin resembles human skin, a much smaller dose is needed. Using a single dose of about 7.25 U/kg in the gel restored the pig’s blood glucose to normal levels. The speed and long-term effects of the gel are found to be comparable to those of “basal insulin shots”. Basal insulin shots deliver a steady dose that stabilises blood sugar levels between meals and overnight. This result raised hopes for the scientists to carry out further research to apply it to humans. Repeated application of gel has not caused any skin irritation or inflammation. Despite these promising results, several challenges remain before clinical application in humans can be considered. The absorption of gel into the bloodstream is slower than that of injection, limiting its usefulness in case of emergencies.
While a 12-hour duration suggests that the gel could serve as a long-acting insulin to provide backend blood-sugar control, patients would still likely prefer a fast-acting dose at mealtimes. The gel has not shown any side effects in mice or pigs, but this does not guarantee that humans will not show any toxicity, particularly when humans use it for decades. These considerations highlight the substantial research still required to achieve safe, effective, and clinically relevant insulin delivery through the skin.
The long-term safety of repeated gel application also remains unknown. Nevertheless, if the results observed in animals translate successfully to humans, needle-free insulin gels could significantly benefit patients with needle aversion, improve treatment adherence, and reduce the burden of diabetes management. Continued research may eventually open a new pathway towards non-invasive diabetes care.
(THE WRITER, AN AUTHOR, WAS EDITOR-IN-CHIEF OF THE JOURNAL SCIENCE AND CULTURE FOR ABOUT TWO DECADES)