Key points

Key points

The content of this evidence summary was up-to-date in June 2017. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Regulatory status: New medicine. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor antagonist. Liraglutide (Saxenda) received a European marketing authorisation in March 2015 and was launched in the UK in January 2017. It is licensed as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adult patients with an initial BMI of:

  • 30 kg/m2 or more (obese), or

  • from 27 kg/m2 to less than 30 kg/m2 (overweight) in the presence of at least one weight-related comorbidity such as dysglycaemia (prediabetes or type 2 diabetes mellitus), hypertension, dyslipidaemia or obstructive sleep apnoea.

Treatment should be discontinued after 12 weeks on the 3.0 mg daily dose (recommended maintenance dose) if patients have not lost at least 5% of their initial body weight.

Liraglutide (Saxenda) is a different licensed product to liraglutide (Victoza) and the doses of liraglutide (Saxenda) used for weight management are different to that used in managing type 2 diabetes (Victoza). Liraglutide (Victoza) has been licensed in the UK for the treatment of type 2 diabetes in adults since 2009. Victoza is not licensed as a pharmacological treatment option for weight management and it also has a different licensed dose range.

Overview

This evidence summary discusses 4 randomised controlled trials (RCTs) in adults who were obese or overweight (BMI 27 kg/m2 or above) with a variety of weight-related comorbidities including dyslipidaemia, hypertension, type 2 diabetes and obstructive sleep apnoea. All of these studies compared liraglutide 3.0 mg daily with placebo and all participants also received lifestyle interventions for weight loss. There are currently no published double-blind RCTs which compare liraglutide with other medicines for weight management.

The main efficacy outcomes from the 4 studies included weight loss outcomes, time to onset of type 2 diabetes and change in apnoea-hypopnea index (AHI; apnoea or hypopnea events per hour of sleep). After 32 to 160 weeks' treatment, there was a statistically significant increased weight loss with liraglutide 3.0 mg daily compared with placebo in all 4 studies (an estimated treatment difference of −5.4 to −4.0% in percentage body weight change from baseline across the 4 studies). However, many participants regained weight after stopping treatment. In 1 study in adults without type 2 diabetes, after 56 weeks' treatment with liraglutide, participants who switched to placebo gained 2.91% bodyweight over the following 12 weeks compared with 0.69% for those who continued on liraglutide.

In 1 study in adults with prediabetes, 2% of participants in the liraglutide group developed type 2 diabetes over a 160‑week treatment period compared with 6% in the placebo group. There was a reduction in the AHI with liraglutide compared with placebo in 1 study in people with obstructive sleep apnoea. However, the clinical significance of this is unclear as there is no established minimum clinically significant difference for this measure.

The European Public Assessment Report (EPAR) for liraglutide (Saxenda) reports that the general adverse event profile is in line with that for liraglutide (Victoza). The EPAR states that there is currently insufficient data to assess if uncommon events (pancreatitis/neoplasms) occur more frequently with liraglutide 3.0 mg daily compared with liraglutide 1.8 mg daily. Liraglutide has been associated with an increase in pulse rate, which the EPAR states does not appear to be dose-related.

The NICE guideline on identifying, assessing and managing obesity (2014) recommends considering pharmacological treatment for people who have not reached their target weight loss or have reached a plateau on dietary, activity and behavioural changes. The guideline recommends orlistat as a pharmacological treatment option only as part of a weight management plan in adults who are obese or have a BMI of 28 kg/m2 or more with associated risk factors, such as type 2 diabetes. Liraglutide (Saxenda) is not specifically mentioned in the NICE guideline, however it is another potential pharmacological treatment option for use in line with its marketing authorisation, for adults for whom lifestyle and behavioural approaches have not been effective and for whom the potential benefits of treatment outweigh the risks. However, as reported in the EPAR for liraglutide (Saxenda) it is unlikely that any potential weight loss achieved with liraglutide would be sustained after treatment is stopped. The summary of product characteristics (SPC) for liraglutide (Saxenda) does not provide further information on how long treatment should be continued for in people who have lost at least 5% of their initial body weight after 12 weeks' treatment. There were high drop-out rates in all of the studies so continuation with treatment may be a problem in practice.

A summary to inform local decision-making is shown in table 1.

Table 1 Summary of the evidence on effectiveness, safety, patient factors and resource implications

Effectiveness

  • In obese or overweight adults without type 2 diabetes, there was a mean change in body weight from baseline of −8.0% with liraglutide 3.0 mg daily (recommended maintenace dose) and −2.6% with placebo (estimated treatment difference:−5.4%, 95% confidence interval [CI] −5.8 to −5.0%, p<0.001). There was also a statistically significant higher percentage of participants in the liraglutide group who lost 5% or more and 10% or more bodyweight from baseline compared with placebo:

    • 63.2% versus 27.1% (odds ratio [OR] 4.8, 95% CI 4.1 to 5.6, p<0.001) for 5% or more and

    • 33.1% versus 10.6% (OR 4.3, 95% CI 3.5 to 5.3, p<0.001) for 10% or more (Pi-Sunyer et al. 2015, RCT, n=3,731, 56 weeks).

  • In obese or overweight adults with type 2 diabetes, there was an estimated mean change in body weight from baseline of −6.0% with liraglutide 3.0 mg daily and −2.0% with placebo (estimated treatment difference:−4.0%, 95% CI −5.1 to −2.9%, p<0.001). There was also a statistically significant higher percentage of participants who lost 5% or more and 10% or more bodyweight from baseline compared with placebo:

    • 54.3% versus 21.4% (estimated treatment difference 32.9%, 95% CI 24.6 to 41.2%, p<0.001) for 5% or more and

    • 25.2% versus 6.7% (estimated treatment difference 18.5%; 95% CI 12.7 to 24.4%, p<0.001) for 10% or more (Davies et al. 2015, RCT, n=846, 56 weeks).

  • In obese or overweight adults with prediabetes, 2% of participants in the liraglutide 3.0 mg daily group developed type 2 diabetes compared with 6% in the placebo group (hazard ratio 0.21, 95% CI 0.13 to 0.34, p<0.0001) [le Roux et al. 2017, RCT, n=2,254, 160 weeks].

  • In obese adults with obstructive sleep apnoea and a baseline AHI of 49.0 in the liraglutide group and 49.3 in the placebo group, there was a mean reduction in AHI of −12.2 events per hour of sleep in the liraglutide group compared with −6.1 events per hour of sleep in the placebo group (estimated treatment difference: −6.1, 95% CI −11.0 to −1.2, p=0.015) [Blackman et al. 2016, RCT, n=359, 32 weeks].

Safety

  • There are several special warnings and precautions for use in the SPC for liraglutide (Saxenda), including warnings on pancreatitis, cholelithiasis and cholecystitis, thyroid disease, heart rate, dehydration and hypoglycaemia in people with type 2 diabetes.

  • In the study in overweight adults with type 2 diabetes there were 5 severe hypoglycaemic events in 3 participants in the liraglutide 3.0 mg daily group, 3 events in 2 participants in the liraglutide 1.8 mg daily group compared with no events in the placebo group. All of these severe hypoglycaemic events occurred in participants who were taking concomitant sulfonylureas (Davies et al. 2015, RCT, n=846, 56 weeks).

Patient factors

  • Liraglutide is given by subcutaneous injection. Orlistat is an oral treatment, which may be preferable to some patients. Orlistat and liraglutide have different adverse effect profiles, which also need to be considered.

  • More participants in the liraglutide 3.0 mg groups withdrew from the studies due to adverse events compared with the placebo groups (from 9.2 to 13.0% with liraglutide 3.0 mg compared with 3.3 to 6.0% with placebo across the 4 studies discussed in the evidence summary).

  • Gastrointestinal disorders were the most common adverse events reported in the studies. Across the studies in the clinical development programme, nausea was reported in 39.3% of participants taking liraglutide 3.0 mg daily compared with 13.8% taking placebo (EPAR: Saxenda).

Resource implications

  • Liraglutide (Saxenda) costs £196.20 for 30 days' supply at the maintenance dose of 3.0 mg daily (MIMS, May 2017, excluding VAT).

  • Orlistat 120 mg 3 times a day costs £18.05 for 30 days' supply (Drug Tariff, May 2017, excluding VAT).

  • The manufacturer has reported that they will only promote the use of liraglutide (Saxenda) on private prescription, so they anticipate that use on the NHS will be limited. This evidence summary does not contain recommendations from NICE on whether the medicine should be prescribed within the NHS or by private prescription.