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02-23-2017 | Prediabetes | Article

Editorial board comment

Liraglutide and the rule of halves

Sanjay Kalra

Comment on: Liraglutide boosts preventive power of lifestyle intervention in prediabetes

Guidelines from the American Association of Clinical Endocrinologists clearly recommend the use of pharmacotherapy in prediabetes with additional risk factors such as obesity. Such an approach is backed by evidence: metformin, pioglitazone, and liraglutide have demonstrated their ability to prevent or postpone diabetes in high-risk individuals. To date, however, the best results have been achieved with lifestyle modification.

Le Roux et al's publication on the 3-year follow-up of the SCALE Obesity and Prediabetes study puts its weight behind the use of liraglutide for type 2 diabetes risk reduction and weight management in individuals with prediabetes.

Apart from the improvement  in weight and glycemia, liraglutide improved other markers of vasculometabolic health. These include fasting insulin, HOMA-IR, systolic blood pressure, and high sensitivity C-reactive protein. Thus, liraglutide can be considered an apt preventive therapy for metabolic syndrome. It must be noted, however, that Le Roux et al prescribed lifestyle intervention counselling once a month, along with liraglutide. This included advice to undergo at least 150 minutes of physical activity a week, and to reduce daily energy intake to 500 kcal below individual requirements. 

We also highlight what we term Liraglutide's Rule of Halves. Only half of all participants completed the trial (791/1505 [47%] of liraglutide-treated participants, 337/749 [55%] of the placebo group). The proportion of placebo-treated participants who withdrew due to adverse events (46/747, 6%) was half that of the liraglutide group (199/1501, 13%). At the same time, only half of all liraglutide-treated participants were able to achieve a sustained weight loss of >5% (49.6%). Of these, another half managed a >10% weight loss (24.8%), and yet another half demonstrated a >15% loss of body weight (11.0%). The proportion of placebo-treated participants who achieved >5% weight loss was half that seen in the liraglutide arm (23.7% vs 49.6%).

The SCALE Obesity and Prediabetes data are encouraging, but remind us that a lot more still needs to be done. The results signal a need for a paradigm drift in our thought process. From secondary prevention (early diagnosis and treatment of disease), we should now move to primary prevention of diabetes (mitigation of risk factors before disease sets in). With lifestyle modification, and liraglutide, we should be able to achieve this in a significant proportion of our patients.

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