Weight loss outcomes and comparisons with other weight management programmes management programmes

To the best of our knowledge, this is the first study to evaluate the effectiveness of each intervention in a real-life weight management programme; whereas, previous studies evaluated a single intervention or programme phases, regardless of the types of interventions.

A tier 3 service of the Fakenham programme (FWMS) reported that 44.1% of all participants and 53.8% of completers lost ≥5% of initial weight after six months (Jennings et al., 2014) (full details in page 70). FWMS offers a lifestyle change for participants to help them achieve their target weight loss over one year. The patients were considered for treatment with orlistat, LELDs or bariatric surgery if they met the clinical criteria. During the period of study, just 36 participants were prescribed orlistat due to a national shortage of the drug; 9 patients were prescribed LELDs. As this study did not report the results for each intervention, it is not possible to compare the results of phase 2 of the GCWMS with FWMS. There are no other tier 3 service providers that have published the outcomes of each intervention.

4.6.2.1 Orlistat

Orlistat (360 mg/day) users in phase 2 had completed the lifestyle intervention in phase 1.

Mean weight loss improved (-1.9 kg) for all 536 participants using orlistat, compared with the same group of participants (-1.4 kg) in the lifestyle phase. In the HTA journal, a previous systematic review of eight RCTs by Avenell et al. (2004) stated that the addition of orlistat to the diet was accompanied by weight loss at 12 months; the mean difference in weight between orlistat plus diet versus placebo plus diet was 3.01 kg (95% CI: 3.48 to -2.54 kg). This suggests that using orlistat after the issuance of dietary advice can improve long-term weight loss.

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While several RCTs have studied the effect of orlistat on weight loss, the majority of them reported the effects on patients who spent at least a year using the drug. A RCT was undertaken to assess the efficacy of orlistat to promote weight loss in patients with a BMI 28-47 kg/m² over 2-years duration (Sjostrom et al., 1998). In total, 743 participants from 15 European centres entered four-week single blind, hypocaloric diet, and then were assigned to orlistat 360 mg or placebo. At the end of the first year, the mean weight change for the orlistat and placebo groups was -10.3 kg and -6.1 kg, respectively. Moreover, the mean weight loss at the end of the first 3 months for the orlistat and placebo group was -7.2 kg and -5.2 kg, respectively.

Another one-year RCT compared the effect of orlistat 360 mg versus placebo on cardiovascular disease in 339 participants with BMIs between 30 and 50 kg/m² from 8 centres in Australia and New Zealand. The mean weight loss at a one-year duration for those who used orlistat in conjunction with a lifestyle change was -4.7 kg (Swinburn et al., 2005). Additionally, based on the HTA programme, a previous RCT by Micic et al. (1999) reviewed the clinical effectiveness of orlistat in the treatment of obesity over 6 months duration. This tested 119 patients with BMI ≥30 kg/m² recruited for a two-week diet and then randomised to receive orlistat 360 mg or a placebo. The mean weight change in the orlistat group was -10.7 kg compared with -7.3 kg in the placebo group (O'Meara et al., 2001). A prospective randomised study was carried out to evaluate the efficacy and safety of orlistat 360 mg in 80 patients with obesity (BMI ≥30 kg/m²) at an outpatient department in India over a 24 week duration. The mean weight change reported was -1.59 kg, -4.65 kg and -5.25 kg at 8 weeks, 16 weeks and 24 weeks, respectively (Jain et al., 2011).

A cohort trial, based on real life data, assessed the effect of orlistat on body weight over 3 years, when delivered in a primary care setting in a UK population. Mean BMI in that study was 37.2 kg/m², and the weight change in the first 4 months for all 99,420 participants was -0.94 kg/month (95% CI: -0.93 to -0.95 kg/month), meaning the patients lost 2.82 kg after 3 months duration (Douglas et al., 2015).

The SIGN guidelines and United States guidelines recommend orlistat for patients with BMI ≥30 kg/m² or 28 kg/m² plus comorbidity, who have not achieved their target weight loss through lifestyle intervention. However, based on the above results, the evidence for the effectiveness of orlistat on obesity depends on the results of RCTs, and it is not known how the efficacy measures in the trials relate to effectiveness in the general population. In

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conclusion, orlistat was approved for obesity treatment based on its positive benefits as established in RCTs; however, in real life, orlistat is associated with a lesser effect on weight loss than in RCTs (Douglas et al., 2015). The current study showed a lower level of weight loss (-3.31 kg within 3 months) than that achieved in RCTs (-7.2 kg at the end of 3 months).

For the subgroup of participants with type 2 diabetes, the current results of the effect of orlistat in real life on weight loss (-2.93 kg (95% CI: -3.8 to -2.0 kg) at 3 months) was less than the weight loss observed in the systematic review and meta-analysis of the RCT (-3.67 kg (95% CI: -4.30 to -3.04 kg) at 3 months) (page 90). In the LOOK AHEAD study, of the 722 individuals who lost less than 5% (at 6 months) of their initial weight after an ILI, 291 patients took orlistat for 6 months and lost an additional 1.8% of their weight (Wadden et al., 2009); a result comparable to GCWMS. This may be because the patients in the GCWMS and the LOOK AHEAD study had first gone through the lifestyle intervention phase and then used orlistat; while the participants in the RCTs underwent lifestyle interventions and took orlistat at the same time. Therefore, the latter may have been on a low-fat diet following the lifestyle intervention and certain fats may need to be present in the diet for orlistat to have effect.

Due to the unpleasant side effects of orlistat, such as oily stools, patients may stop taking this medication. A longitudinal study undertaken by Hollywood and Ogden (2011) recruited 566 individuals who was prescribed orlistat by their GP and were registered on the Xenical support system. These patients completed a baseline questionnaire within the first three months of starting the treatment and filled up a follow-up questionnaire after six months. Patients who stopped taking the medication by six months, those who continued taking the medication and those who reported flexible adherence based on their diet were grouped as non-adherers, adherers and lifestyle adherers, respectively. The researchers found that within six months, 47.5%, 30.4% and 22.1% could be classified as non-adherers, adherers and lifestyle non-adherers, respectively. Therefore, it is recommended that clinicians should not focus only on advising patients about the consequences of eating a high fat diet, but should also promote healthy dietary changes and inform patients about the effectiveness of this kind of medication on weight management. Also, it is important that health care professionals, GPs, patients, and policy makers understand the possible effects of orlistat use as part of the protocol in routine weight management services.

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To date, a number of trials appear to have suggested that LCD (800-1800 kcal/day) is associated with modest weight loss (5-6%) at 12 months duration. A previous systematic review and meta-analysis of 80 RCTs after ≥1-year follow-up by (Franz et al., 2007) reported weight loss at 6, 12, 24, 36, and 48 months for different interventions. The intervention for 51 studies was diet alone, and the mean weight losses at 6, 12, 24, and 48 months was -4.9, -4.6, -4.4, and -3.0 kg, respectively. Moreover, a previous RCT, performed in three hospitals in the Netherlands and two hospitals in Poland reported a weight change at 12, 24 and 36 months of female patients with obesity and breast cancer.

The mean weight difference between the treatment group and the control group at 12 months was -6.2 kg (95% CI: -9.0 to -3.4 kg); however, the sample size for the study was small, reflecting the wide confidence interval (De Waard et al., 1993). Additionally, a recent RCT was conducted in the Netherlands on 57 participants with BMI =28-35 kg/m² with no comorbidities randomised to a LCD (1,250 kcal/day) for 12 weeks. It found the mean weight change was -8.2 kg (Vink et al., 2016); whereas, the mean weight change in the current study for a group of participants (n =1,043) selecting LCD (600 kcal deficit diet) was -2.39 kg. However, the aforementioned trial suffered from a small sample size in contrast with the current research and different methodological used.

In the lifestyle phase, LCD was selected by the patients; however, in phase 2, a prescribed LCD was offered to the patients, giving a daily meal plan. The participants in the current study were recruited for lifestyle interventions for 4 months prior to the selected LCD, and they had lost -1.89 kg (95% CI: -2.0 to -1.7 kg). This might reflect the fact that this group of participants were less motivated to lose weight. Furthermore, some of the participants suffered from diabetes, which may have caused more modest weight loss, as it is known that people with type 2 diabetes lose less weight than those without diabetes (Stanford et al., 2012). Based on the above and the intensity of the programme (monthly follow up), those who selected LCD as part of a routine weight management programme were less likely to lose weight compared to those in RCTs. Although, in GCWMS, this was effectively rescue therapy; i.e. giving prescribed LCD to those who had failed to lose weight.

A RCT undertaken by Jakicic et al. (2012) was conducted with 363 individuals who were overweight or obese with a BMI in the range of 25-40 kg/m². Of these individuals, 198 were allocated randomly to a stepped-care weight loss intervention (STEP), while 165

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were allocated randomly to a standard behavioural weight loss intervention (SBWI).

Although the intervention combining physical exercise, a hypocaloric diet and counselling on a week or month basis for a year and a half was applied to participants in both groups, the programme was fixed in the case of the SBWI group, while the programme could be adjusted according to weight reduction goals in the case of the STEP group. The results revealed that, upon completion of the year-and-a-half programme, the SBWI group achieved a higher average weight reduction than the STEP group, with an average weight difference of -1.3 kg (95% CI: -2.8 to 0.2 kg). The weight percentage decreased by -8.1%

(95% CI: -9.4% to -6.9%, p ˂0.001) and -6.9% (95% CI: -8.0% to -5.8%, p ˂0.001) in the SBWI group and the STEP group, respectively.However, the real interest is in the rate of success of the intensification of the programme; despite 5 steps to intesify the programme including phone counselling and liquid meal replacements, only 5% of the participants moved back to the target weight loss trajectory during the study. Therefore, it could be concluded that rescue interventions may not work.

With regard to the difference between men and women in terms of weight loss, a previous study by Wamsteker et al. (2005) recruited 66 participants with obesity (48 women and 18 men) to be treated in an outpatient clinic in the Netherlands from September 2000 to June 2001 for 8 weeks. They were treated by LCD (800-1000 kcal/day) with meal replacement and the mean weight change was 10.2%. Moreover, there was no significant difference between men and women in terms of percentage weight loss, which concurs with the current research finding (2.41 kg (95% CI: 2.8 to 1.9 kg) in men and 2.38 kg (95% CI: -2.7 to -2.0 kg) in women).

4.6.2.3 FWL

The current study shows that participants who did well in the lifestyle phase were offered FWL and continued to lose weight in phase 2, but their weight loss in this phase was not considerable (-1.9 kg) compared with (-8.27 kg) in the lifestyle phase. The possible reasons might be the higher number of sessions in the lifestyle phase (fortnightly) compared with phase 2 (monthly). However, this group of participants were still more motivated to lose weight than those who selected orlistat or LCD, as 83% had lost at least 5 kg weight by the end of the lifestyle phase. After that, weight loss plateauing might be expected at the end of phase 2, and patients may experience some difficulties in losing weight. An example from the systematic review and meta-analysis of long term RCTs, found weight loss starts to plateau across all interventions after 6 months. For example, when adding exercise to LCD,

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this resulted in a mean weight loss of -7.9 kg at 6 months, then plateaus at -6.7 kg at 12 months (Franz et al., 2007). Unfortunately, the data did not explain the reasons why those who were selected for the FWL lost more weight in the lifestyle phase when compared with those in the LCD and orlistat group in phase 2. Behaviour and psychological effects may be suggested as possible reasons for this. In addition, it could be that the members in the group selected for the FWL were heavier (mean BMI was 42.8 kg/m²), more motivated and more likely to be male (33.9%) than the members of the groups who were offered orlistat or LCD.

4.6.3 Completion and weight loss outcomes for subgroups

Among those participants offered FWL and who completed the lifestyle phase and phase 2 of the programme, 86.5% lost their target weight (≥5 kg); demonstrating they had met their target and achieved further meaningful weight loss (95% CI: -11.5 to -10.7 kg). Overall, the patients who completed the programme by attending ≥7 sessions in the lifestyle phase and ≥2 sessions in phase 2 lost more weight than the non-completers; however, a minority of people who used orlistat or LCD also lost their target weight. This might be due to the higher threshold for completion applied, and the assumption that attendance is directly correlated with weight loss. 45.2%, 48.4% and 37.3% of the patients offered orlistat, LCD, and FWL respectively, did not complete the requisite number of sessions. This might be because they did not reach their weight loss target, or due to the limited choices of appointment times and the service design.

The findings showed that the patients without diabetes lost more weight than patients with diabetes when selecting FWL in phase 2; this is likely to be due to differences in dietary adherence, as suggested in the previous chapter, or might be because most of the patients were using anti-diabetic drugs, a common side-effect of which is weight gain. In addition, patients with diabetes might suffer from other complications, such as neuropathy, foot ulcers or heart disease. Therefore, increasing physical activity, which is an important aspect of the treatment of patients with obesity, is usually unsuccessful. However, there was no difference between the weight losses of people with and without diabetes offered orlistat or LCD, possibly because those with diabetes were successful at remembering to take the orlistat tablet with their anti-diabetic medication. This research and that in the previous chapter explored the effects of gender, SIMD, age and initial BMI on weight change. A previous study by Stubbs et al. (2011) reviewed the rate and extent of weight loss in a primary care/commercial weight management partnership system of 34,271

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participants referred to Slimming World; it was found that regardless of sex, age and initial weight, if a patient is able to complete a programme of treatment and is encouraged to achieve reasonable weight loss in the first week, they will be likely to succeed in achieving their target weight loss.