Data on FDA-approved weight management medications dominate Obesity Week
Focus on Obesity
Last year was a pivotal year for approvals of weight management medications, with naltrexone plus bupropion (Contrave—Takeda) and liraglutide (Saxenda—Novo Nordisk) approved for chronic weight management in September and December, respectively. These two approvals were added to the drugs already marketed for weight management and weight loss—specifically, phentermine plus topiramate (Qsymia—Vivus) and lorcaserin (Belviq—Arena)—giving clinicians greater therapeutic options to help patients reach an ideal body weight.
Numerous presentations were focused on data evaluating these four agents for weight management at the 2014 Obesity Week meeting, held November 2–7 in Boston, which combines both the American Society for Metabolic and Bariatric Surgery (ASMBS) and the Obesity Society (TOS) annual meetings. For more information on presentations covering a variety of topics focused on weight management, visit the ObesityWeek abstract archive: http://obesityweek.com/abstract-information/abstract-archive/ and the journal, Obesity: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1930-739X.
New Phase III data for liraglutide showed that this agent produced weight loss across a range of body mass index (BMI) categories and improved health-related quality of life.
An analysis of the SCALE (Satiety and Clinical Adiposity—Liraglutide Evidence in Non-diabetic and Diabetic people) Obesity and Pre-diabetes trial was conducted to assess the efficacy and safety of once-daily liraglutide 3 mg, given as an adjunct to a 500 kcal/d diet and exercise program, on weight management in patients across a variety of baseline BMI subgroups. Patients with a BMI of 27 kg/m or more and one or more comorbidities or those with a BMI of 30 mg/kg or more were randomized 2:1 to active treatment with liraglutide 3 mg daily (n = 2,487) or placebo (n = 1,244) and assessed at week 56.
Across all baseline BMI categories (≤29.9 kg/m, 30–34.9 kg/m, 35–39.9 kg/m, and ≥40 kg/m), use of liraglutide resulted in a similar body weight loss. Almost all patients given liraglutide lost weight (92%) compared with 65% of patients in the placebo group. Body weight loss of 5% or more, 10% or more, and 15% or more occurred in 63%, 33%, and 14% of patients given active treatment compared with 27%, 11%, and 3.5% of patients given placebo, respectively (P < 0.0001 for all three comparisons). Liraglutide was well tolerated, with gastrointestinal disorders the most common events reported.
An assessment of the impact of liraglutide on health-related quality of life was also conducted for patients in the SCALE trial. The Impact of Weight on Quality of Life (IWQoL), Short-Form (36) Health Survey (SF-36), and Treatment Related Impact Measure—Weight (TRIM-W) questionnaires were used to assess health-related outcomes. The investigators reported that weight loss was accompanied by improvements in the total IWQoL score with liraglutide (10.6 ± 13.3) compared with placebo (7.6 ± 12.8; P < 0.0001), which was mostly driven by improved physical function. In addition, the TRIM-W total score, the SF-36 summary physical/mental health scores, and all domain scores of the IWQoL and SF-36 improved with liraglutide compared with placebo.
Naltrexone plus bupropion
Two separate analyses assessing the effects of naltrexone plus bupropion were presented, with one concluding that the efficacy of this agent is unrelated to race or ethnicity and the other showing that naltrexone plus bupropion has a direct effect on controlling cravings in patients.
A subanalysis of the COR-BMOD (A Safety and Efficacy Study of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects Participating in an Intensive Behavior Modification Program) study, a 56-week, randomized, placebo-controlled trial that examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD), was conducted to determine the effects of naltrexone plus bupropion in white (n = 313) and African American (n = 70) patients. In the original trial, naltrexone plus bupropion significantly reduced body weight compared with placebo, and more patients in the naltrexone plus bupropion group who completed the trial achieved a 56-week weight loss of 5% or more and 10% or more compared with placebo (P < 0.001).
Baseline characteristics for the white and African American patients were similar in terms of body weight (approximately 100.5 kg) and BMI (36.5 kg/m), but age differed slightly between the groups (white, 48.7 y; African American 44.5 y). After 56 weeks, the placebo weight loss response was more robust in white patients (−9.2% vs. −4.9%), but weight loss was similar between the two groups after placebo correction (−4.0% white vs. −4.3% African American). In addition, safety was similar between groups in terms of the frequency and pattern of adverse events and serious adverse events. The authors concluded that the efficacy of naltrexone plus bupropion is unrelated to race or ethnicity.
An integrated analysis of four 56-week Phase III trials of naltrexone plus bupropion was conducted to assess the effects of this agent on the Cravings and Mood Sub-scales of the Control of Eating questionnaire (CoEQ) and its relationship with weight loss. Principal components of the CoEQ included Craving Control, Craving for Sweet, Craving for Savory, and Positive Mood. The analysis was conducted in patients who completed 56 weeks of treatment with naltrexone plus bupropion (n = 1,238) or placebo (n = 720) and had weight and CoEQ measurements at baseline and week 56.
The investigators reported that use of naltrexone plus bupropion resulted in improved Craving Control and Craving for Sweet compared with placebo, which was independent of weight loss. They concluded that these findings suggest that naltrexone plus bupropion has a direct effect on cravings.
Phentermine plus topiramate
Two separate analyses of Phase III data showed that use of phentermine plus topiramate resulted in improved metabolic syndrome parameters in patients with a BMI of 35 kg/m or more and was safe and effective in overweight patients aged 65 years and older.
A pooled analysis of data from two 56-week Phase III trials, EQUIP (Controlled-release Phentermine/Topiramate in Severely Obese Adults: A Randomized Controlled Trial) and CONQUER (Effects of Low-dose, Controlled-release, Phentermine Plus Topiramate Combination on Weight and Associated Comorbidities in Overweight and Obese Adults), was conducted to assess the effects of phentermine plus topiramate, given as an adjunct to lifestyle modifications, on weight loss and metabolic syndrome parameters in 2,695 patients with a BMI of 35 kg/m or more. At baseline, patients had a mean weight of 114 kg, a waist circumference of 120 cm, systolic blood pressure of 126 mm Hg, fasting glucose of 100 mg/dL, and cholesterol levels of 49 mg/dL for high-density lipoprotein (HDL) and 143 mg/dL for triglycerides. Treatment with three different doses of phentermine plus topiramate resulted in weight loss effects of −5.1% to −10.8% compared with −1.8% for placebo. In addition, changes in waist circumference, systolic blood pressure, HDL, triglycerides, and fasting glucose levels were all significant compared with placebo.
A post-hoc analysis of the SEQUEL (Two-year Sustained Weight Loss and Metabolic Benefits with Controlled-release Phentermine/Topiramate in Obese and Overweight Adults) trial, which was a 52-week continuation phase to the CONQUER trial, was conducted to assess the effects of phentermine plus topiramate in a small subpopulation of 64 patients aged 65 years and older (age range at baseline, 65.2–70.8 y). At baseline, patients had a mean weight of 101 kg, a BMI of 36 kg/m, and a number of comorbidities, such as hypertension (67%), dyslipidemia (39%), prediabetes (50%), and type 2 diabetes (20%). After a total of 108 weeks of treatment, least-squares mean weight loss was −8.0% to −11.4% in the phentermine plus topiramate groups compared with −4.3% in the placebo group. In addition, the annualized rate of type 2 diabetes in those without the disease at baseline was lower in patients given active treatment compared with placebo.
Two post-hoc analyses of data from three Phase III trials showed that use of lorcaserin helped more obese patients shift into the overweight category, and it may be considered a viable treatment option in severely obese patients for presurgery weight loss or as a potential alternative to surgery.
Data from the BLOSSOM (Behavioral Modification and Lorcaserin Second Study for Obesity Management), BLOOM (Behavioral Modification and Lorcaserin for Overweight and Obesity Management), and BLOOM-DM (Behavioral Modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus) trials were analyzed to assess the effects of lorcaserin 10 mg, given twice daily, compared with placebo in patients who were obese at baseline.
Patients were classified into three categories: class I obesity (30–34.9 kg/m), class II obesity (35–39.9 kg/m), or class III obesity (≥40 kg/m). After 52 weeks of treatment, more patients in the lorcaserin groups achieved BMI levels of less than 30 kg/m compared with placebo. Lorcaserin was particularly effective at shifting patients who were classified as class I obesity at baseline, with or without type 2 diabetes, into the overweight category. The investigators concluded that these effects may potentially result in decreased weight-related health risks.
In another analysis of the same three trials, the effect of lorcaserin in patients with severe obesity was assessed. Severe obesity was defined as a BMI of 40 kg/m or more or a BMI of 35 kg/m or more plus one obesity-related comorbidity. The investigators noted that mean weight loss was greater in patients given lorcaserin compared with placebo (−5.9% vs. −2.6%), and more patients in the lorcaserin group achieved BMI levels of less than 35 kg/m at week 52 compared with placebo. In addition, an assessment of the percentage of patients who lost 5% or more weight at week 12 showed that 47.3% of patients in the lorcaserin group achieved this endpoint compared with 21.9% of patients in the placebo group.