Greater access to weight-loss drugs has sparked concerns. Regulatory prudence will be key

Generic drugs transformed access to essential medicines that were unaffordable for people suffering from serious diseases. Their impact on the global HIV-AIDS pandemic was profound. Since 2000, access to antiretroviral drugs dramatically increased, reaching millions of HIV-infected persons in developing countries. India’s generic drug industry played a major role in this.

In 1970, India substituted “process patenting” for “product patenting”, giving a marked fillip to the production of generics in pharmaceutical manufacturing. Thereafter, India became the acclaimed “pharmacy of the world”. As the prototype GLP-1 agonist drug semaglutide goes off patent, many Indian drug manufacturers are rushing to benefit from the burgeoning domestic market for the drug. They can also flood the global supply chain with generic versions that will cost only 25-30 per cent of their current price.

The Doha Declaration, adopted by the World Trade Organisation in 2001, permits countries to relax patent rules to counter major public health threats. Cardiovascular diseases and diabetes now constitute a “slow motion public health emergency”. Together, they are the leading cause of death worldwide, accounting for 23,000,000 to 25,000,000 deaths annually. In India, these disorders account for a third of all deaths. Tragically, many of these deaths occur prematurely in the 40-69 year age group.

While healthy diets, regular physical activity and avoidance of exposure to tobacco smoke are essential to prevent and control these disorders, many affected persons have high levels of body fat, which makes control of diabetes or pre-diabetes, hypertension and abnormal blood lipids difficult. This is especially a problem with inflammation stoking abdominal fat deposits — a common feature among Indians. GLP-1 agonists effectively overcome this.

However, these drugs also come with several potential adverse effects. These include gastrointestinal side effects (nausea, bloated stomach, pancreatitis), mental health disturbances (anxiety, depression), visual disturbances (optic neuropathy) and bone thinning with risk of fractures. While many of these occur in a small proportion of users, a common side effect is loss of skeletal muscle (sarcopenia) which accompanies fat loss. Sarcopenia has been reported in 25-40 per cent of persons taking these drugs. This can be a serious problem in Indians, who generally have a low lean muscle mass. This can result in falls due to loss of stabilising muscle strength. The young must be aware of the possible side effects to sexual health.

Discontinuation of these drugs, after achieving desired weight loss, has been widely reported to result in rebound weight gain and loss of cardio-metabolic health benefits. This is especially true of persons who do not adhere to healthy diets or regular physical activity, believing that the drugs have permanently cast away body fat. Prolonged therapy may be needed, with high financial costs and adverse drug effects. Use of leptin, an appetite-suppressing hormone, has been suggested for long-term therapy after initial therapy with semaglutide. As yet, that is uncharted territory.

The levels of benefits and risks associated with these relatively recent drugs still need to be carefully assessed in our patient population. So, regulatory caution is fully justified. The use of these drugs should be guided by medical wisdom and regulatory prudence. As Louis Pasteur advised his students, “keep your enthusiasm but let strict verification be its constant companion”.

The writer is chancellor, PHFI Institute of Public Health Sciences, and chair, Centre for Universal Health Assurance at the Indian School of Public Policy