GLP-1 Drugs Prove Effective For Obesity But Access Remains Unequal

Three Cochrane reviews reveal that GLP-1 receptor drugs lead to clinically meaningful weight loss, though questions persist about potential biases and long-term impacts. These reviews were commissioned by the World Health Organization to guide upcoming recommendations on the use of these medications in obesity treatment (1^✔ ✔Trusted Source
Semaglutide for adults living with obesity

Go to source). The analyses assessed three GLP-1 receptor agonists and found that each contributed to notable weight reduction compared to placebo. However, uncertainties remain about sustained outcomes, adverse effects, and potential conflicts of interest linked to industry-funded trials.

Development and Broader Use of GLP-1 Receptor Agonists

Glucagon-like peptide-1 receptor agonists were initially introduced in the mid-2000s to manage type 2 diabetes. Among individuals with diabetes, especially those with heart or kidney conditions, these medications enhanced blood sugar regulation, reduced cardiovascular and renal complications, encouraged weight loss, and lowered early mortality rates.

In recent years, GLP-1 receptor agonists have been explored for obesity treatment. These medications imitate a natural hormone that slows digestion and promotes longer feelings of fullness. In the United Kingdom, they are authorized for weight control alongside calorie reduction and physical activity in individuals with obesity or overweight conditions linked to health problems.

GLP-1 Drugs Show Promise for Weight Reduction

Across the reviews, tirzepatide, semaglutide, and liraglutide all produced considerable weight loss over one to two years compared with placebo, with sustained benefits likely during ongoing treatment.

Tirzepatide, administered once per week, resulted in around a 16% decrease in weight after 12 to 18 months. Data from eight randomized controlled trials involving 6,361 participants indicated these effects could persist for up to 3.5 years, though long-term safety information was limited.

Semaglutide, also injected weekly, lowered body weight by about 11% after 24 to 68 weeks, with evidence suggesting sustained effects up to two years, based on 18 randomized controlled trials involving 27,949 participants. It significantly increased the likelihood of achieving at least a 5% weight reduction but caused more frequent mild-to-moderate digestive side effects.

Liraglutide and Safety Observations

Liraglutide, given as a daily injection, produced a modest average weight loss of approximately 4–5%, as shown in 24 trials with 9,937 participants. Even so, it improved the proportion of individuals achieving meaningful weight reduction relative to placebo. Data on benefits beyond two years were limited.

Across all reviews, there was minimal or no difference between the drugs and placebo concerning major cardiovascular events, quality of life, or mortality. However, adverse effects, especially nausea and gastrointestinal discomfort, were more frequent among participants using GLP-1 drugs, leading some to discontinue treatment.

Need for Independent Evidence and Fair Access

According to Juan Franco from Heinrich Heine University Düsseldorf, these medications can bring substantial weight reduction, particularly within the first year, marking a breakthrough after years of limited success in obesity treatment options.

Most of the reviewed studies received funding from pharmaceutical manufacturers, who were heavily involved in study design, analysis, and publication. This situation raises potential conflicts of interest and highlights the importance of independent investigations.

Affordability and Global Representation Challenges

The authors emphasized that widespread adoption must consider social and economic factors such as affordability, insurance coverage, and accessibility to prevent widening existing health inequalities. High prices currently restrict access to semaglutide and tirzepatide, whereas liraglutide has become more affordable since its patent expired. Semaglutide’s patent will expire in 2026.

The studies reviewed were primarily conducted in middle- and high-income nations, with limited representation from regions like Africa, Central America, and Southeast Asia. Given global differences in body composition, diet, and health behavior, the authors stressed the necessity of understanding how these medications function across diverse populations.

Eva Madrid from the Universidad de Valparaíso, Chile, highlighted that more evidence is needed on long-term cardiovascular outcomes, especially in lower-risk individuals. She noted that regaining weight after discontinuation might affect the durability of observed benefits. More independent, publicly funded studies are crucial to guide public health and clinical decisions.

Commissioned by the World Health Organization, these Cochrane reviews will shape forthcoming WHO recommendations on the use of GLP-1 receptor agonists for managing obesity. The guidelines are expected to be released soon following a public consultation held in September.

In conclusion, the Cochrane reviews shows that GLP-1 receptor drugs can significantly aid in weight loss, yet their long-term safety, accessibility, and equitable use require further exploration through independent research. These insights will guide forthcoming World Health Organization recommendations aimed at responsible and fair use of these medications for obesity management.

Reference:

1. Semaglutide for adults living with obesity - (https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015092.pub2/full)

Source-Medindia