Glycaemic effects of weight loss drug locaserin reduce diabetes risk

Obesity

By Mardi Chapman

12 Oct 2018

Modest weight loss associated with the use of lorcaserin has been shown to improve metabolic health in overweight and obese people with or at high risk for diabetes and adverse cardiovascular events.

The findings with the serotonergic agonist are consistent with other evidence such as the DiRECT trial that weight loss can help with remission with type 2 diabetes.

Presented at the European Association for the Study of Diabetes (EASD) meeting, the results are from the international CAMELLIA-TIMI 61 study which randomised 12,000 people with a BMI ≥27 to either lorcaserin or placebo in addition to a standardised weight management program.

Lorcaserin resulted in a modest additional weight loss of about 3 kg at one year and greater reductions in BMI, waist circumference and waist-to-hip ratio than placebo.

People with prediabetes treated with lorcaserin had a 19% reduction in diabetes compared to the control group while people with diabetes at baseline had a significant reduction in HbA1c.

“Fasting plasma glucose and the homoeostatic model assessment of insulin resistance were significantly improved with lorcaserin compared with placebo in patients with diabetes or prediabetes, with the largest between-treatment differences noted in patients with diabetes at baseline,” said the study investigators, which included Professor Tony Keech, deputy director of the NHMRC Clinical Trials Centre at the University of Sydney.

Glucose-lowering medication use was lower in patients treated with lorcaserin than in the placebo group and lorcaserin also reduced the risk of diabetic microvascular complications by 21% in patients with diabetes at baseline.

Interestingly, the study showed reductions in glycaemic parameters as soon as three months into treatment and in advance of maximal weight loss.

The study investigators said the 5-HT2C receptor agonist was effective for weight loss and ‘unlike many other obesity medications to date, has proven safety for major adverse cardiovascular events, including cardiovascular death, myocardial infarction, or stroke’.

“Taken together, these findings reinforce the notion that modest, durable weight loss can improve cardiometabolic health and supports the role of lorcaserin as an adjunctive therapy in chronic management of weight and metabolic health.”

Professor Ian Caterson, from the Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders at the University of Sydney, told the limbic the findings confirm that weight loss helps people with diabetes or prediabetes.

“Lorcaserin doesn’t achieve spectacular weight loss – 2-3 kg above placebo – but even those extra kilos produce quite good but not spectacular changes in diabetes.”

“So we know from the previous diabetes prevention studies that if you are at high risk of diabetes and you lose 4 kg you can prevent 60% of the diabetes.”

“Weight loss in type 2 diabetes or in those at risk of diabetes is really important and anyway you achieve it is effective. It has a metabolic effect on blood pressure, on diabetes, on sleep apnoea. Any weight loss is good.”

He said the big problem in Australia was that weight loss drugs were not on the PBS.

“Even if it gets approved, it will be costly. We don’t have a history of funding these drugs – I suppose because they are thought of as lifestyle drugs.”

“One of the things we hope will change is that people will see that these sort of benefits for people with diabetes do save money.”

A Comment article in The Lancet said intermittent treatment with lorcaserin might be considered.

“Physicians might be uncomfortable prescribing lorcaserin on a general basis and might instead prefer to prescribe it on a temporary basis (ie, for 6–12 months); patients who respond well and for whom treatment should be continued could be identified within the first few months of treatment.”

They added that targeting specific subpopulations such as emotional eaters might also be effective given what was known about lorcaserin decreasing brain responses to food-related signals as well as emotional and limbic activity.

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