Coming soon: Newer weight loss cum diabetes drugs. Will they be more effective and lasting?

An interesting, novel approach is to combine Semaglutide with another new molecule – Cagrinitide (Cagri- Sema). This produces greater weight loss than Semaglutide alone says Dr Ambrish Mithal, Chairman, Endocrinology and Diabetes, Max Healthcare

2023 also saw data from studies using 25 and 50 mg oral Semaglutide with results comparable to the injectable version. (Representational Photo)

Written by Dr Ambrish Mittal

If someone has diabetes, weight reduction can lead to better glucose control and reduce the risk of long-term complications. However, it is a challenge to control glucose level and lose weight simultaneously when treating diabetes. Medications that are effective in controlling glucose often lead to weight gain — insulin, sulphonylureas and glitazones being some examples. On the other hand, the relatively recent GLP1 receptor agonists and SGLT2 inhibitors promote weight loss.

GLP 1 (glucagon-like peptide-1) is a hormone secreted by our intestine and binds to a specific receptor in the pancreas, promoting insulin secretion and suppressing glucagon secretion. GLP1 also acts in the brain, where it induces early satiety, thereby reducing food intake. As Semaglutide, it revolutionized weight loss stories in 2023. Tirzepatide, which acts via two receptors – GLP1 and GIP – was approved for treating obesity in the US and is superior to Semaglutide for weight loss. Recent evidence suggests that the new class of drugs reduces cardiac events by 20 per cent, both in people with and without diabetes, and slows down kidney disease, mainly because of reduction in urinary protein loss.

Also Read | Can this cheaper diabetes and weight loss injectable drug, now available in India, work for you?

What does 2024 have in store? Some drugs that act via two or even three receptors may reach clinical usage stage in 2024/25. The dual receptor Servodutide, which acts on GLP1 and glucagon receptors, has been shown to reduce weight by as much as 15 -20 kg. The most anticipated drug is Retatrutide, which was developed as a triple receptor agonist (GLP1, GIP and glucagon). Clinical results show that Retratutide can reduce weight by approximately 25 per cent at 48 weeks! All participants lost at least five per cent body weight. Acting via the glucagon receptor induces satiety and enhances energy expenditure. Adding glucagon activity increases liver fat clearance in a way not seen before, and potentially could turn out to be a powerful drug for fatty liver too. Retatrutide is unlikely to reach the stage of commercial production for the next two to three years.

2023 also saw data from studies using 25 and 50 mg oral Semaglutide with results comparable to the injectable version. It’s very likely the future will see higher doses of oral Semaglutide in clinical use. An interesting, novel approach is to combine Semaglutide with another new molecule – Cagrinitide (Cagri- Sema) which produces greater weight loss than Semaglutide alone. Orforglipron is an orally administered partial GLP1 agonist that resulted in weight loss of 14.7 per cent or 15 kg at 36 weeks. Yet another remarkable development is the monoclonal antibody Bimagrumab, which causes fat loss while helping increase muscle mass.

This year sounds exciting for medication related to diabetes and obesity. However, do not take them without medical supervision as some of them have side effects, like nausea, vomiting and stomach paralysis. They should not be taken by those with a history of pancreatitis or a family history of certain types of thyroid cancer. Besides, about 20 per cent of the weight loss is muscle, so regular exercise is essential. Not all users lose weight and there is the issue of how long they should be taken for. Newly emerging data shows that the weight tends to come back once the drug is discontinued unless backed by major lifestyle modifications.