Weight Management and the Role of Medications

Australia is today ranked as one of the most obese nations in the developed world, with the prevalence of obesity rising significantly over the past decade. Based on measured height and weight from the 2011–12 Australian Bureau of Statistics Australian Health Survey to calculate BMI, it is estimated that almost 2 in 3 adults are overweight or obese (10% more than in 1995) and an estimated 1 in 4 children are overweight or obese1. Excess weight, especially obesity, is a major risk factor for cardiovascular disease, Type 2 diabetes, some musculoskeletal conditions and some cancers. As the level of excess weight increases, so does the risk of developing these conditions. Pharmacists are ideally placed in the community to help educate patients about healthy lifestyle strategies and as medication experts, are well versed to talk to patients about the role that medications may play as potential causes of weight gain and as treatment options for weight management.

Measuring obesity

For obesity to occur there must be either an increase in energy intake over our body’s needs or a decrease in energy expenditure (or both). There can be a large inter-person variation in total body fat stores as well as in body fat distribution. It is recognised that ‘abdominal’ or ‘central’ accumulation of fat is associated with a greater risk developing weight-related diseases1. A healthy weight range can be defined as the body weight, adjusted for height with the most widely used weight-to-height ratio being the Body Mass Index (BMI), defined as: BMI = Body weight (Kg) / Height (m2). The risk of metabolic complications and the classification of weight status according to BMI is summarised below (Table 1).

The ‘healthy’ BMI range is based on a number of studies which indicate that BMIs in that range are associated with the lowest death rate – however there is considerable debate as to whether the BMI ranges for overweight and obesity used for Caucasians are appropriate for those of Asian origin and Indigenous Australians as some evidence shows that they may have a greater risk of disease at lower BMI’s4.

The need to measure central (abdominal or visceral) adiposity in clinical assessments is not in dispute, as this is strongly associated with metabolic disease, particularly tye-2 diabetes, dyslipidaemia, hypertension and cardiovascular disease. The simplest measure of this is waist (abdominal) circumference – Men at increased risk have waist circumference measuring >94cm (substantially increased at >102) and women at increased risk have a waist circumference measuring >80cm (substantially increased at > 88cm)2. Waist-to-hip ratio may also be used as a measure of abdominal obesity.

Medicines and Weight Gain

Whilst there may be many possible factors (genetic, environmental and behavioural) that could play a role in the development of obesity, an area of particular importance in the pharmacy setting is being aware of medications which may cause weight gain. Some medications may cause weight gain through mechanisms such as increasing appetite, reducing satiety, changing basal metabolism or by altering/limiting levels of activity. Some commonly prescribed examples include3,5;

• Anti-seizure medication eg. Valproate
• Antidepressants: TCA’s, some SSRI’s (paroxetine, citalopram, sertraline)
• Antipsychotics: (See table 2 on the right)
• Antidiabetic agents eg. Sulfonylurea’s and Thiazolidinediones
• Alpha-blockers
• Beta-blockers
• Corticosteroids
• Insulins
• Lithium
• (Some) oral contraceptives

Antipsychotics and Metabolic Syndrome

Antipsychotic medications are widely prescribed and have a varying potential to cause weight gain, hyperglycaemia, hypertension and hyperlipidaemia – collectively described as ‘metabolic syndrome’, ‘Syndrome X’ or insulin-resistance syndrome. The life expectancy of patients with schizophrenia (even after controlling for the risk of suicide) is shortened by up to 25 years compared to the general population due to cardiovascular co-morbidities and the estimated risk of diabetes in people with psychosis is 2-6 times higher than the general population6. Physical inactivity and unhealthy eating are extremely common in people with psychosis, contributing to obesity and hyperlipidaemia is an early metabolic response to some antipsychotics causing low-levels of High density lipoprotein (HDL) and raised triglycerides6,7.

While there is some debate regarding the degree to which antipsychotics contribute to cardio-metabolic risks, there is a generally accepted hierarchy of drugs which promote weight gain (see Table 2) in the short term while longer term impacts are somewhat less clear (as patients with persistent psychosis are generally on lifelong maintenance therapy). Additionally, patients with complex mental health conditions are also likely to be treated with other commonly prescribed medications which may contribute to weight gain and the potential for medication-related weight gain should be considered as cumulative.

Lifestyle interventions to assist in weight management are the same for patients taking antipsychotics as the general population (see weight management strategies below), with a particular emphasis on behavioural interventions for weight loss showing the best reductions in weight gain for patients starting on antipsychotics9. Should lifestyle interventions be unsuccessful, pharmacotherapeutic interventions may include switching antipsychotic medications (under a switching protocol determined by a psychiatrist or specialist) where appropriate, to another antipsychotic with a lower potential for weight gain8.

Weight Management Strategies

There are multiple approaches to weight management strategies, and often patient’s need to navigate their way through traditional approaches and the transient ‘fad diet’ phenomena. Pharmacists are ideally placed in the community to provide support and advice in helping patients find an approach that will be suitable for them or aid in putting patients in contact with other health professionals who can assist, such as dieticians and exercise physiologists.

It is important to consider weight management strategies with patient’s holistically, with tailored solutions rather than a one-size-fits-all approach. Some important points to emphasize at the outset of weight management strategies include;

• Understand that everybody’s weight loss journey is individual; avoid comparing needs and approaches of others, as these will often differ from your own
• Modest weight losses of around 5-10% of body weight can produce significant health benefits, with reductions in cardiovascular risk, control of diabetes, increased fertility and improved quality of life10.
• The main goal of any weight loss strategy should be an improvement in health, with some specific and measurable goals being; A reduction in blood pressure (a 4-5kg reduction in weight can improve blood pressure by 8-9mmHG11), improved lipid profile and improved glycaemic control (a 7-10% reduction in weight can reduce fasting plasma glucose values by >25%11).

Lifestyle interventions

Behavioural change programs to alter eating habits and to increase activity are the basis on which successful weight management therapies are built. Encouraging patients to reduce their intake of saturated fats whilst increasing their intake of fibre and carbohydrates with a low glycaemic index (GI) is important.Protein intake can also be increased if desired. Maintenance of weight loss in the long term is best achieved with a reduction in fat intake10.

Increasing activity in patients can start slowly where required, increases in incidental exercise (daily activities, walking to work, walking up stairs etc.) can be quite useful for some. The incorporation of a specific exercise program tailored to the individual’s capability and needs is also a highly effective weight loss and lifestyle intervention.

When behavioural changes are made as part of lifestyle interventions, follow up with patients around what has been implemented, what is working and what the barriers are important to achieve longer term success. Motivational interviewing techniques and strategies to gauge an individual’s readiness to change can be useful tools for pharmacists who are implementing structured weight management services or in general counselling support of patients who are trying to manage their weight.

Pharmacological management

Whilst any approach to weight management should be multi-faceted, drug therapy and/or formulated meal replacements may be considered as part of an overall strategy for patients, particularly if diet and exercise interventions alone are insufficient.

CNS Stimulants: Phenteramine is a sympathomimetic agent similar in nature to amphetamines, but with a modified structure which lowers is potential for abuse. Phenteramine works by decreasing appetite, it is approved for short term use (up to 3 months) as there are no studies which show efficacy in use of greater than 1 year5,12. Despite not having the same abuse potential as other amphetamines, common adverse effects can still include sleeplessness, palpitations, dry mouth, nervousness and irritability5.

Orlistat: Orlistat is a lipase inhibitor which induces fat malabsorption if excess fat is consumed. Consumption of a high-fat meal may induce significant fatty diarrhoea and faecal incontinence, approximately one third of total fat intake is not absorbed at a dose of 120mg three times daily5. It is indicated for patients with a BMI of >30 (or BMI > 27 for patients with hypertension, type 2 diabetes and dyslipidaemia2,5). It is contraindicated for use in patients with chronic pancreatitis or other comorbidities causing malabsorption, it is not recommended in pregnancy and is not indicated for use in children2. The adverse effects caused by excess intake of fat are to aid patients in recognizing their fat intake and learning to avoid hidden fats. In patients with reduced levels of fat soluble vitamins (A,D,E,K), vitamin supplements may be necessary as an adjunct2.

Selective Serotonin Reuptake Inhibitors (SSRIs): Some selective agents such as fluoxetine and sertraline may be of benefit in the treatment of obesity if depression is also evident13. At usual doses, effective treatment of depression symptoms may facilitate adherence to lifestyle counselling interventions to assist with weight management13.

Meal Replacements: Very Low Energy Diets (VLEDs) are designed to either totally replace meals, or replace at least one meal per day, with the use of these products being recommended for patients in the treatment of obesity (BMI > 30) as part of a weight management strategy by the NHMRC research council for the treatment of obesity10. Some systemic reviews have shown the efficacy of meal replacement products for effective weight loss14,15, however as with all strategies meal replacements should be considered in conjunction with effective lifestyle interventions, behavioural change management and increased physical activity.

Bulking agents: Methycellulose and other bulking agents have been used to reduce food intake, however there is little evidence of reduction in hunger or increased satiety and they have not demonstrated any long term benefit in weight management5.

Key Points for Patients

As frontline healthcare providers with patient trust and rapport, pharmacists have an opportunity to assist patients in managing their weight safely and effectively with individually tailored advice and support. Some key points to pass on to patients when it comes to effective weight management include;

• Weight loss and weight maintenance is best achieved through a multi-faceted approach, incorporating behavioural change, dietary modification and increases in physical activity.
• Some medications may contribute to weight gain and adopting effective weight management strategies may help counteract these effects, patients should be referred to their prescriber to discuss their options should lifestyle interventions alone be ineffective with their medication related weight gain.
• The goals of weight management strategies should be aligned with the overall goal of better health, reduction of obesity-related disease risk and long-term improvements to quality of life as opposed to short term or ‘quick fix’ strategies.

Assessment Questions

The assessment questions below can be found at the Guild Pharmacy Academy myCPD e-learning platform. Login or register at: www.mycpd.org.au

1. Which of the following statements regarding measurement of obesity is correct?
   a. It is recognised that ‘abdominal’ or ‘central’ accumulation of fat is associated with a lower risk developing obesity-related diseases
   b. Men have a substantially increased risk of weight-related diseases when waist circumference is > 80cm
   c. Women have a substantially increased risk of weight-related diseases when waist circumference is >88cm
   d. Waist-to-hip ratio is not an accepted clinical measure for waist circumference
2. You undertake a BMI assessment for a patient who presents at your pharmacy with the following measurements; weight 104kg, height 1.74m. Considering BMI alone, which of the following statements regarding the patients BMI classification and risk of metabolic complications is correct?
   a. Obesity (class II), severe risk
   b. Overweight, increased risk
   c. Obesity (class I), moderate risk
   d. Morbid obesity, very severe risk
3. Which of the following is NOT a mechanism by which medications can contribute to weight gain?
   a. Increases in satiety
   b. Changes to basal metabolism
   c. Increases in appetite
   d. Prohibiting or limiting physical activity
4. Which of the following medications is most likely to cause medication-related weight gain and metabolic syndrome?
   a. Ziprasidone
   b. Olanzapine
   c. Paliperidone
   d. Asenapine
5. Which of the following statements regarding pharmacological interventions for weight management is INCORRECT?
   a. Phenteramine is only indicated for short term use (3 months), to reduce appetite and assist with weight management
   b. Vitamin A, D, E and K supplementation may be required for patients who undertake weight management treatment with orlistat, as the medication may cause reduced levels of these fat-soluble vitamins.
   c. Sertraline is an accepted treatment to aid in weight management where depression is also evident
   d. Orlistat is only indicated for treatment of childhood obesity in patients with a BMI of greater than 27

References 
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10. National Health and Medical Research Council. Clinical practice guidelines for the management of overweight and obesity in adults. Canberra: NHMRC; 2004.
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12. eTG complete [internet]. Melbourne: Therapeutic Guidelines Limited; 2014 Nov
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15. Brown T, Avenell A, Edmunds LD, et al. Systematic review of long-term lifestyle interventions to prevent weight gain and morbidity in adults. Obes Rev 2009 Nov;10(6):627–38.