ype 2 diabetes mellitus (T2DM) is a condition that can be managed by both oral (taken by mouth) and injectable medications. Injectables can be broadly divided into insulin and non-insulin agents. One type of injectable non-insulin agents is called glucagon like peptide-1 (GLP-1) agonist or mimetics. They act in the same way (mimic) as naturally occurring incretin hormones from the gut. Incretins stimulate insulin secretion after oral intake of glucose. The insulin secretion in response to incretin can be 2-3 times higher. In obesity, the incretin effect is diminished.

It is worth mentioning that GLP-1 mimetics are not first-line agents in the treatment of T2DM. These agents are used when diet, lifestyle and oral anti-diabetic medications have failed to control blood sugar. This medicine also promotes weight loss in obese subjects.

In 2005, the first GLP-1 mimetic approved by the United States Food and Drug Regulatory Authority (FDA) for use in the treatment of T2DM was exenatide. There are many types of GLP-1 mimetics available in the market. They come in the form of injections as once-daily, twice-daily or once-weekly regimens. They are not considered safe in pregnancy and must be discontinued. In terms of side effects, pancreatitis is a known one and hence contra-indicated in patients who have a history of it.

Semaglutide is an anti-diabetic medication developed by Novo Nordisk in 2012 and approved by the FDA for use in the treatment of T2DM in 2017. Its oral version was approved in 2019. Injectables are used once weekly, whereas oral tablets are taken once a day. Semaglutide has also been used in the management of obesity in overweight patients alongside lifestyle modifications like exercise and a healthy, low-calorie diet. One can expect to lose up to five per cent of their body weight in a month on semaglutide. The weight loss is more rapid in the initial months of treatment, but later, it plateaus.

A recent article in The Times (UK) highlighted a study that suggested that the loss of appetite from semaglutide leading to weight loss can result in the loss of healthy muscle and bone mass in some individuals. This is worrying and needs further evaluation.

In terms of affordability, GLP-1 mimetics are expensive medications and in regions with high out-of-pocket costs, it may be outside the reach of many. Initiating such a group of costly medications in people with T2DM in low- and middle-income countries is challenging due to poor access to health services and the lack of a structured primary healthcare system.

Existing low levels of education and socio-economic status further exacerbate problems related to disease management. One of the adverse consequences of fragmented healthcare systems is poor disease management and treatment of T2DM. Inappropriate medication use and prescribing combined with poor continuity of care can lead to insufficiently managed chronic diseases and the development of complications.

Excessive use of GLP-1 agonists has led to the promotion of its falsified versions in the local markets, including online availability. The Drug Regulatory Authority of Pakistan (DRAP) released an alert in July 2023 about such products. It advised use of registered/ approved brands on prescription only.

Management of diabetes requires the involvement of a multidisciplinary team comprising of nutritionists, primary care physicians, nurse practitioners, pharmacists and specialists. Initiation of GLP-1 mimetics requires close monitoring of blood glucose in addition to patient education about their condition and how the medicine works.

There is a need for information leaflets that are easy to interpret and preferably in local languages.

It is worth noting that modifications in dietary habits and physical activity remain the main form of treatment for T2DM and obesity; however, pharmacological interventions are at times needed. It is imperative that the management of diabetes and its complications, including its pharmacological recommendations and interventions at the primary care level, be evidence-based, cost-saving and cost-effective.

The writer is an associate professor in family medicine at Health Services Academy, Islamabad