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Obesity: Are we one step closer to beating it?: Dr Aneesh Basheer

M3 India Newsdesk Mar 21, 2022

This article speaks about how weight loss goals may be achieved with potential pharmacological treatments and therapies.

Key takeaways

  1. GLP-1 receptor agonists are effective agents for weight loss in obese patients who are candidates for drug therapy.
  2. Semaglutide given 2.4 mg subcutaneous weekly must be considered the first-line agent since it produces greater weight loss and is more convenient to administer compared to liraglutide.


Obesity is a major public health problem worldwide and contributes to excess mortality and morbidity among adolescents and adults. Of late, it has been recognised more as a disorder of body weight regulation rather than an isolated lifestyle disease [1].

Besides, there appears to be a strong genetic background to the risk of developing obesity. As of 2015, about 604 million adults were estimated obese, reflecting a doubling in the prevalence of obesity since 1980. Studies have shown health benefits with as low as 5% reduction of body weight [2].

Most clinicians and experts consider a 10% or more reduction of body weight as an excellent goal. However, the goal needs to be decided based on the risk for major adverse health outcomes especially cardiovascular. In general, Asians are believed to be at risk at lower levels of BMI (> 23 kg/m2). In addition, a high waist circumference may predict excess cardiovascular risk despite a normal BMI.

Pharmacological treatment for weight loss

Current guidelines strongly recommend pharmacologic treatment for weight loss in persons with a BMI of 35-40 kg/m2 [3]. While is advisable to consider drug therapy in those with BMI 30-35 kg/m2 and those with BMI 27-29.9 kg/m2 with additional cardiovascular risk factors. In those who are candidates for drug therapy, several options are available including GLP-1 receptor agonists (liraglutide, semaglutide), orlistat, phentermine, topiramate and bupropion-naltrexone combination. Direct comparisons between these drugs are limited and studies indicate that all of them are effective for weight loss [4].

While Orlistat was used widely due to the availability of long-term trials showing good safety, it is commonly associated with gastrointestinal side effects. Other drugs like phentermine also have concerns related to cardiovascular side effects and are not considered first-line agents.

The GLP-1 receptor agonists have therefore emerged as first-line drugs in candidates who are eligible for drug therapy. Liraglutide was the first such agent approved for obesity treatment, administered at a maximum dose of 3 mg daily. Its weight lowering effect is independent of glycemic control and has been demonstrated in non-diabetic individuals as well. In addition, liraglutide reduces cardiovascular events in diabetics (trials testing this effect in non-diabetic obese individuals are lacking).

The STEP 8 randomised controlled trial

In a recent landmark study, in STEP 8 randomised controlled trial, investigators compared once-daily liraglutide 3 mg subcutaneously with weekly subcutaneous semaglutide 2.4 mg in 338 adults with BMI of 30 kg/m2 or more [5].

Both groups received lifestyle modifications. At the end of 68 weeks, patients in the semaglutide lost 15.8% of body weight while those on liraglutide lost 6.4% of body weight. In other words, weekly semaglutide resulted in 10% excess weight loss compared to daily liraglutide. Similar to liraglutide, major cardiovascular benefits have been demonstrated with semaglutide among individuals with type 2 diabetes.

Its effect on cardiovascular events among obese non-diabetics is being studied currently. In most trials with semaglutide, the side effects are mild with improvement on continued use. They include:

  • Nausea
  • Diarrhoea
  • Vomiting

The once-weekly subcutaneous dosing is likely to be a game-changer for pharmacologic treatment of obesity in eligible patients. With the pandemic of metabolic syndrome and obesity posing a major public health challenge, the availability of highly efficacious, easy to administer and safe drugs is the need of the hour.

STEP 8 trial provides good evidence for using once-weekly semaglutide as the first-line agent for drug therapy of obesity. If cardiovascular benefits of semaglutide in diabetics are replicated in non-diabetic obese patients, the use of this drug will not only reduce weight but also ameliorate cardiovascular risk associated with obesity.

Click here to see references


Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

The author, Dr Aneesh Basheer is an Academician Professor of Medicine from Kerala. He is an expert reviewer of international peer-reviewed medical journals and case reports.


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