Effects of a novel combination of orlistat and acarbose on tolerability, appetite, and glucose metabolism in persons with obesity

Abstract

Objective: There is an unmet medical need for a safe and effective weight loss product with minimal systemic side-effects. In this study, the effect of a novel modified-release fixed-dose combination of orlistat and acarbose (MR-OA) was compared with conventional orlistat (CO) regarding tolerability, appetite and glucose metabolism.Methods: Sixty-seven men with obesity, aged 24 to 60 years with body mass indexes (BMIs) 33 to 40 kg m −2 or BMIs 30 to 32 kg m −2 and waist circumference above 102 cm were included. They were randomized to either three different doses of the test formulation MR-OA (60 mg orlistat/20 mg acarbose, 90/30 and 120/40) or CO (Xenical, 120 mg orlistat) for a 2-week study of daily treatment. The participants spent days 1 and 14 at the clinical research centre where they received standardized meals, had blood sampling and filled in questionnaires regarding tolerability and appetite after meals. In days 2 to 13, the participants were at home and continued to fill in the questionnaires daily.Results: In the MR-OA groups, reports of liquid and oily stools as well as faecal incontinence were fewer, whereas reports of gastric distension and flatulence were higher, compared with the CO group. More participants reported decreased hunger in the 90/30 and 120/40 MR-OA, and postprandial plasma glucose concentration was reduced in all MR-OA groups compared with CO.Conclusions: This study shows that by using a modified-release dosage form, orlistat and acarbose can be combined without compromising tolerability. Furthermore, MR-OA shows promising effects regarding reduction of appetite and reduces postprandial glucose. Tolerability is coupled to compliance and thereby efficacy of a treatment; therefore, this novel combination MR-OA could be an effective approach for Abbreviations: CRC, clinical research centre; GI, gastrointestinal; GLP-1, glucagon like peptide-1; LOCF, last observation carried forward; MR-OA, multiple release orlistat acarbose; TID, three times a day; VAS, visual analogue scale.

Safety of a Novel Weight Loss Combination Product Containing Orlistat and Acarbose

“…16 Acarbose plasma concentrations are difficult to measure due to a lack of ionized functional chemical groups within the molecule; therefore, bioequivalence in glucose-lowering capability is the usual way of determining an acarbose effect. 18,19 In the previous study, 5 we showed an expected effect on plasma glucose concentration, which was similar to that reported with conventional oral product of acarbose, 20 a sign that the MR-OA formulation does not affect acarbose absorption.…”

“…These 3 dose strengths were given to the 3 treatment groups; group I, II, and III, respectively, a conventional orlistat product, that is, Xenical, 120 mg was used as comparator (Table 1), denoted in group IV. A detailed description of the study was published previously 5 . Ethics approval was granted by the regional Ethical Review Board in Uppsala, Sweden (dnr 2016/257).…”

“…Included in the study were obese male White subjects 24‐60 years old with either a body mass index (BMI) of 32–40 kg/m 2 or BMI of 30–32 kg/m 2 together with waist circumference >102 cm. Subjects were screened for eligibility as per study‐specific inclusion/exclusion criteria within 5 weeks before (days –35 to –4) randomization and the first oral administration of the test and reference products 5 . Additional inclusion criteria were based on medical history, physical findings, vital signs, electrocardiogram (ECG), and blood chemistry values at the time of screening.…”

“…4 We recently showed that a novel multiple-unit modified-release (MR) capsule with a fixed-dose combination of orlistat and the carbohydrate-digestion inhibitor acarbose (MR-OA) reduced appetite and postprandial glucose. 5 We also found that the oral MR formulation enabled combining these 2 active pharmaceutical ingredients (APIs) without worsening gastrointestinal tolerability compared with the approved conventional orlistat drug product. 5 Here, we present pharmacokinetic data from the clinical study EP-001 for obese middle-aged men treated with the novel capsule, administered 3 times .00 (5.88-6.00) 6.00 (6.00-6.00) 6.00 (6.00-6.00) 6.00 (6.00-6.00) t max , h-V 4 6.00 (4.90-6.00) 6.00 (6.00-6.00) 6.00 (6.00-6.00) 6.00 (6.00-6.00)…”

“…We recently showed that a novel multiple‐unit modified‐release (MR) capsule with a fixed‐dose combination of orlistat and the carbohydrate‐digestion inhibitor acarbose (MR‐OA) reduced appetite and postprandial glucose 5 . We also found that the oral MR formulation enabled combining these 2 active pharmaceutical ingredients (APIs) without worsening gastrointestinal tolerability compared with the approved conventional orlistat drug product 5 …”