When to consider antiobesity drugs or bariatric surgery

Diabetes and Primary Care, Summer, 2007 by Jonathan Pinkney, David Kerrigan

Most people with type 2 diabetes are either overweight or obese, and many are severely so. Although the potential benefits of weight loss for people with type 2 diabetes are profound, weight loss is seldom a major treatment goal, and many diabetes-trained healthcare professionals remain ill-equipped to help patients tackle their obesity. This article examines the current evidence for offering antiobesity drugs or bariatric surgery in the routine management of type 2 diabetes and suggests when and in whom these treatment modalities should be considered.

Key words

- Obesity

- Bariatric surgery

- Antiobesity agents

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Obesity is intimately linked with type 2 diabetes (Colditz et al, 1995; Chan et al, 1994), and the overwhelming majority of people with type 2 diabetes are overweight or obese. In a recent survey of people with type 2 diabetes attending a secondary care diabetes clinic in Liverpool, as few as 14% had a healthy BMI, while 52% had a BMI >30kg/[m.sup.2], 24% had a BMI >35g/[m.sup.2], and 8.1% a BMI >40kg/[m.sup.2] (Daousi et al, 2006). In the same study it was found that the presence of obesity was associated with poorer glycaemic control, increased needs for other drug therapy, and further exacerbated the risks of hypertension, dyslipidaemia and macrovascular disease. These prevalence figures far exceed the prevalence of obesity in the background population predicted from the Health Survey for England (The Information Centre, 2006), and show also that severe obesity (BMI >40kg/[m.sup.2]; grade 3 or morbid obesity) is now commonplace among people with type 2 diabetes, particularly in women--a striking and poorly understood finding. Despite the many advances in diabetes care over the last three decades, life expectancy for middle-aged people with diabetes remains lower than the population average by, on average, 8 years (Roper et al, 2001). Clearly, more effective control of type 2 diabetes has become a national imperative and there is now increasing interest in weight loss as a means to achieve this.

Short-term experimental studies in people who are overweight with established type 2 diabetes clearly showed that weight loss restores blood glucose and insulin sensitivity to near-normal (Henry et al, 1986). A variety of other studies of intensive dietary interventions--alone or in combination with exercise or behavioural therapy--also demonstrate improved glycaemic control in obese individuals with type 2 diabetes (Pinkney and Wilding, 2004). Furthermore, epidemiological data suggest that weight loss reduces mortality in people with diabetes by around one quarter (Williamson et al, 2000). It would follow that the ideal treatment to prevent and control diabetes would emphasise caloric restriction, physical activity and weight loss. So, what do antiobesity drugs and bariatric surgery have to offer?

Antiobesity drugs

Currently, there are three antiobesity drugs licensed in Europe for long term treatment--orlistat (Xenical; Roche, Welwyn Garden City), sibutramine (Reductil; Abbot, Maidenhead) and rimonabant (Acomplia; Sanofi-Aventis, Guildford).

Orlistat is an inhibitor of intestinal and pancreatic lipases and can result in a 30% reduction in the absorption of dietary fat.

Sibutramine is a drug that acts on the brain to inhibit re-uptake of the neurotransmitters serotonin and norepinephrine and is believed to exert its effects by increasing satiety and enhancing energy expenditure after meals.

Rimonabant is a cannabinoid receptor antagonist that reduces body weight mainly by reducing appetite, through an action on the reward centres in the brain. Rimonabant reduces appetite by suppressing the pleasurable aspect of eating, and also appears to have a variety of peripheral actions to reduce body fat and favourably influence the metabolic syndrome (Padwal and Majumdar, 2007). Rimonabant was licensed in 2006 for use as an adjunct to diet and exercise for the treatment of obese or overweight patients with associated risk factors, such as type 2 diabetes or dyslipidaemia.

NICE has previously summarised much of the evidence on the use of orlistat and sibutramine (NICE, 2001a; 2001b) and updated its review in 2006 (NICE, 2006), although these documents relate principally to people without diabetes and do not specifically address the potential role of antiobesity drugs in diabetes management. Although rimonabant has not yet been considered, we recommend it is used in a similar way to orlistat and sibutramine. The NICE guidance endorses the selective use of orlistat and sibutramine in highly motivated individuals treated in the context of an expert, structured, multidisciplinary management programme. What defines such a programme has been set out in the Royal College of Physicians 2003 report (Table 1).

When to consider an antiobesity drug for a patient with type 2 diabetes

For all people newly diagnosed with type 2 diabetes it is appropriate to ask the question: 'would this particular individual benefit from a management programme that prioritises weight reduction and is there a realistic chance that the treatment could work?' If that question can be answered affirmatively--which it often can be--then antiobesity drugs are one set of tools to be considered.

However, before an antiobesity drug is considered the first steps in weight management should always be non-pharmacological. Without this, drug treatment is likely to be ineffective and a waste of resources. As emphasised by Karen Allan (Allan, 2005), it is vital to identify patients who are motivated and ready to change their behaviour and set weight loss as a long-term priority. This approach has been endorsed by both Dietitians in Obesity Management and the National Obesity Forum, the latter of which have produced an educational CD-ROM on the subject (see Alan, 2005, for more information).

In further support of the development of behaviour-based approaches to the control of type 2 diabetes, provocative preliminary data from the Look Ahead study in North America (Pi-Sunyer, 2006), presented at the American Diabetes Association conference in 2006, suggested that average weight loss of around 8% could be achieved in people with type 2 diabetes, even in those treated with oral hypoglycaemic agents or insulin. Although such responses will only be reproduced in selected individuals, they confirm a degree of reversibility in the metabolic disarray of type 2 diabetes and the power of behavioural approaches to achieve weight loss and treatment goals in motivated people with type 2 diabetes.