Could one daily pill narrow the diabetes treatment gap in the Global South?

Medication that has been a lifeline for patients with uncontrollable diabetes is now slowly shifting from injections to pills, a move that could fundamentally alter treatment for the disease – and who can access it. This shift could also affect the treatment of obesity, a long misunderstood condition once associated with overeating and laziness, rather than the metabolic disorder it is now recognised as.

GLP-1 receptor agonists therapy isn't new. The first FDA-approved drug, Exenatide, hit the market in 2005 and was followed by Liraglutide in 2009, which was seen as a revolutionary alternative to insulin. But the market has until recently been dominated by weekly injections like Ozempic and Wegovy (semaglutide), and Mounjaro (tirzepatide).

Now, once-daily oral GLP pills are emerging as an alternative, especially for the diabetes-stricken Global South. Oral once-daily pills of the same wonder drug could make access more affordable, and less reliant on the cold chain that GLP-1 injections and insulin depend on – and that are harder to secure in emerging economies.

Global burden of disease

One in nine people in the world between the ages of 20-79 lives with diabetes, and one in eight people globally is obese. The GLP injections come with a high price tag and are often not covered by insurance companies, which treat them as an elective drug.

In the United States, Eli Lily's Mounjaro costs about $500 for a month's worth of doses; in the UK, about 199 pounds ($264); and in Saudi Arabia, 1,261 riyals ($336). In India, the brand is locally manufactured and available at 14,766 rupees ($157). In Pakistan, the imported Mounjaro is a whopping 220,000 rupees ($723), while the locally manufactured Tirzepatide from Getz Pharma costs 17,000 rupees ($61).

Pakistan has the highest diabetes prevalence in the world – 31.4 percent of its population suffer from the disease – followed by the Marshall Islands (25.7 percent) and Kuwait (25.6 percent). Many other Middle Eastern countries rank among nations with the highest diabetes prevalence.

For many countries in the Global South, the relative affordability of oral GLP drugs, where the locally manufactured oral semaglutide is about $18 for a 30-day supply, could make them more accessible for diabetes and obesity patients, remove the need for refrigeration and make rural distribution easier.

Treatment revolution

Dr Zakir Alavi is an endocrinologist in Karachi, Pakistan and has been treating patients with diabetes and obesity for nearly 30 years. Pakistan is a country of contrast. We have, on one hand, childhood malnutrition, underweight, and stunted growth. On the other hand, we have childhood and adult obesity, said Alavi. And surprisingly, there is at least some element in the adult and childhood obesity which can be linked to a malnourished mother, and an underweight, premature baby.

Alavi said GLP drugs – whether the injectables or pills – have revolutionised the management of type 2 diabetes and obesity. They not only help type 2 diabetes patients manage their weight, but can also help non-diabetics tackle obesity, improving cardiac and renal outcomes, liver disease, obstructive sleep apnea and osteoarthritis.

Rayaz Malik is a professor of medicine at Weill Cornell Medical College Qatar, and a senior consultant at Hamad Medical Corporation in Doha. Malik has been at the front line of helping patients with diabetes and obesity, and he echoed Alavi's views. We looked at how much weight you need to lose to cure diabetes, the magic number seemed to come in at around 15kg, at least, he said, speaking of research on the subject.

Scientific breakthrough

Jens Juul Holst is one of the central scientists behind the GLP revolution that has given millions around the world a way to live with diabetes and, for those struggling with obesity, a chance to reclaim their bodies. A professor, physician and physiologist, Holst lives in Copenhagen and began his journey with gut hormones in the 1970s.

When we discovered this, what we found was an insulin-releasing peptide from the gut, Holst told Al Jazeera. We were interested in what regulates insulin secretion, and that was as a physiological mechanism because we had some people who were developing too low blood glucose levels, [which is called] hypoglycemia, and we were looking for a peptide that could create insulin release stimulation and then be responsible for the low glucose levels.

Holst and his team's discovery led to what is now known as semaglutide, which paved the way for another drug, tirzepatide, and a third drug called retatrutide that is currently undergoing trials with a potential release in 2027. Eli Lilly and Novo Nordisk, two of the primary manufacturers, expect the GLP market to jump from $80bn per year to $135bn by 2030.

Mechanism and access

Injectable GLP medicines, particularly tirzepatide and semaglutide, remain the most effective treatments because they provide the strongest evidence for long-term weight loss and cardiovascular benefits. The human gut releases a hormone called GLP-1 when we eat. As blood sugar rises, GLP-1 instructs your pancreas to release insulin. GIP is a gut hormone also released when we eat. Like GLP-1, it tells the pancreas to release insulin as blood sugar rises.

GLP-1 also slows how quickly food leaves your stomach, helping you feel full. GLP-1 medicines, therefore, mimic the hormone's effects to lower blood sugar and reduce appetite. Semaglutide works on one receptor, while tirzepatide works on two receptors, making it more effective.

Oral GLP-1 medicines promise the convenience of a pill without sacrificing much of the weight-loss effect, but they still face one major hurdle: the stomach. Unlike injections, which deliver the drug directly into the body, oral semaglutide must survive digestion before a small fraction is absorbed. That is why it must be taken on an empty stomach and at a higher dose.