Physicians' Academy for Cardiovascular Education

Long term GLP-1 agonist treatment provides health benefits for prediabetics

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

le Roux CW, Astrup A, Fujioka K, et al. - The Lancet 2017; published online ahead of print

Background

Liraglutide 3 mg administered subcutaneously once-daily leads to weight loss through reduced appetite and energy intake. It is approved as adjunctive therapy on top of a reduced-calorie diet and increased physical activity program [1,2]. The effects of liraglutide were assessed in obese and overweight individuals with prediabetes and other comorbidities, for the duration of 56 weeks (SCALE Obesity and Prediabetes study) [3].

In this 3-year study extension, the effect of liraglutide 3 mg therapy on the onset of type 2 diabetes mellitus (T2DM), weight loss and safety was evaluated in 2 254 individuals with prediabetes. Patients were randomised 2:1 to either liraglutide or placebo. Those who completed 56 weeks of treatment continued for an additional 104 weeks, allowing for a total of 160 weeks of treatment. Subsequently, there was a 12-week off-treatment follow-up period (until week 172). At week 160, the mean of all continuous variables at multiple time points was calculated.

Main results

Conclusion

3 years of treatment with once-daily subcutaneous liraglutide 3 mg on top of a reduced-calorie diet and increased physical activity, reduced the risk of T2DM in overweight or obese individuals with prediabetes and led to greater weight loss and improvements in glycaemic control and CV risk factors compared with placebo. This data support the hypothesis that long term liraglutide therapy provides additional health benefits to a specific group of high-risk individuals.

Editorial comment

In their editorial article [4], Farr and Mantzoros comment that the important finding of the le Roux et al study is the normalisation of glucose values in prediabetes patients treated with liraglutide. However, they note that this may not be the most cost-effective way for the management of prediabetes, since lifestyle modification is less expensive, non-interventional and appears to be equally effective.

The authors conclude: ‘Whether liraglutide is more effective in the longer term (e.g. 10 years) or whether other GLP-1 analogues are more effective than lifestyle modification alone also remains to be seen. These considerations should be weighed carefully in terms of future recommendations for the treatment of patients with prediabetes in the clinic.’

References

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Find this article online at The Lancet