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- Grudén, Stefan, et al.
(författare)
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Safety of a Novel Weight Loss Combination Product Containing Orlistat and Acarbose.
- 2021
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Ingår i: Clinical Pharmacology in Drug Development. - : John Wiley & Sons. - 2160-763X .- 2160-7648. ; 10:10, s. 1242-1247
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Tidskriftsartikel (refereegranskat)abstract
- The safety of a novel modified-release oral capsule with orlistat and acarbose (MR-OA) was investigated in 67 obese middle-aged White men with a body mass index of 32 to 40 kg/m2 or 30 to 32 kg/m2 plus waist circumference >102 cm. The purpose of this investigation was to compare MR-OA with the existing conventional orlistat regarding systemic safety defined as plasma orlistat concentration at the end of the treatment period of 14 days. Participants took the MR-OA fixed-dose combination formulation 3 times a day together with a major meal. Three different doses of MR-OA were evaluated-60/20, 90/30, and 120/40 (mg orlistat/mg acarbose)-as well as 1 reference group who received the conventional orlistat, Xenical, with 120 mg of orlistat. Blood plasma was sampled on days 1 and 14. The orlistat plasma concentrations of the MR-OA dose showed a delayed absorption and were lower compared with conventional orlistat at the end of the study. All doses were safe and well tolerated without any unexpected adverse events and no serious adverse events. The delay in the rise of orlistat plasma concentration indicates that the modified-release properties of the MR-OA formulation are effective. The systemic exposure of orlistat resulting from MR-OA was similar, albeit a bit lower than the conventional orlistat with 120 mg of orlistat. We can therefore assume that the safety profile regarding the orlistat moiety of MR-OA is comparable to the conventional orlistat and a promising approach for weight control in obese patients. Further clinical evaluation is underway.
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| 2. |
- Holmbäck, Ulf, et al.
(författare)
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Effects of a novel combination of orlistat and acarbose on tolerability, appetite, and glucose metabolism in persons with obesity
- 2020
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Ingår i: Obesity Science & Practice. - : WILEY. - 2055-2238. ; 6:3, s. 313-323
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Tidskriftsartikel (refereegranskat)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 weight loss treatment. A follow-up study in a more diverse population and for a longer duration with weight loss as primary outcome variable is planned.
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| 3. |
- Holmbäck, Ulf, et al.
(författare)
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Effects of a novel weight-loss combination product containing orlistat and acarbose on obesity : A randomized, placebo-controlled trial
- 2022
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 30:11, s. 2222-2232
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management.
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| 4. |
- Vahlberg, Birgit, 1964-, et al.
(författare)
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Effects on walking performance and lower body strength by short message service guided training after stroke or transient ischemic attack (The STROKEWALK Study) : a randomized controlled trial
- 2021
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Ingår i: Clinical Rehabilitation. - : Sage Publications. - 0269-2155 .- 1477-0873. ; 35:2, s. 276-287
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate whetherdaily mobile-phone delivered messages with training instructions during three months increase physical activity and overall mobility in patients soon after stroke or transient ischemic attack.DESIGN: Randomised controlled trial with intention-to-treat analyses.SETTING: University hospital. Data collection from November 2016 until December2018.SUBJECTS: Seventy-nine patients (mean (SD) age 63.9 (10.4) years, 29 were women) were allocated to either intervention (n = 40) or control group (n = 39). Participants had to be independent (modified Ranking Scale ⩽2) and able to perform the six-minute walking test at discharge from the hospital.INTERVENTIONS: The intervention group received standard care and daily mobile phone instructional text messages to perform regular outdoor walking and functional leg exercises. The control group received standard care; that is, primary care follow-up.MAIN MEASURES: Walking performance by six-minute walking test (m), lower body strength by five times chair-stand test (s), the short physical performance battery (0-12 points) and 10-metres walk test (m/s) were assessed at baseline and after three months.RESULTS: The estimated median difference in the six-minute walking test was in favour of the intervention group by 30 metres (95% CI, 55 to 1; effect size 0.64; P = 0.037) and in the chair-stand test by 0.88 seconds (95% CI, 0.02 to 1.72; effect size 0.64; P = 0.034). There were no differences between groups on the short physical performance battery or in 10-metres walking time.CONCLUSIONS: Three months of daily mobile phone text messages with guided training instructions improved composite mobility measures; that is, walking performanceand lower body strength.CLINICAL TRIAL REGISTRY: The study is registered with ClinicalTrials.gov, number NCT02902367.
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| 5. |
- Vahlberg, Birgit, 1964-, et al.
(författare)
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Potential effects on cardiometabolic risk factors and body composition by short message service (SMS)-guided training after recent minor stroke or transient ischaemic attack : Post hoc analyses of the STROKEWALK randomised controlled trial
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate effects of mobile phone text-messaging exercise instructions on body composition, cardiometabolic risk markers and self-reported health at 3 months after stroke.Design: Randomised controlled intervention study with per-protocol analyses.Setting: University Hospital in Sweden.Participants: Seventy-nine patients (mean (SD) age 64 (10) years, 37% female) ≥18 years with good motor function (modified Rankin Scale ≤2) and capable to perform 6 min walking test at hospital discharge were randomised to either intervention (n=40) or control group (n=39). Key exclusion criteria: Subarachnoid bleeding, uncontrolled hypertension, severe psychiatric problems or cognitive limitations.Interventions: The intervention group received beyond standard care, daily mobile phone instructional text messages to perform regular outdoor walking and functional leg exercises. The control group received standard care.Main outcome measures: Fat mass and fat-free mass were estimated by bioelectric impedance analysis. Cardiometabolic risk factors like blood lipids, glycated haemoglobin and blood glucose were analysed at baseline and after 3 months.Results: Both groups changed favourably in fat-free mass (1.83 kg, 95% CI 0.77 to 2.89; p=0.01, effect size (ES)=0.63 vs 1.22 kg, 95% CI 0.39 to 2.0; p=0.05, ES=0.54) and fat mass (-1.30 kg, 95% CI-2.45 to-0.14; p=0.029, ES=0.41 vs-0.76 kg, 95% CI-1.74 to 0.22; p=0.123, ES=0.28). Also, many cholesterol related biomarkers improved; for example, total cholesterol-0.65 mmol/L, 95% CI-1.10 to-0.2; p=0.06, ES: 0.5 vs-1.1 mmol/L, 95% CI-1.47 to-0.56; p>0.001, ES=0.8. However, there were no between-group differences. At 3 months, 94% and 86%, respectively, reported very good/fairly good health in the text messaging and control groups.Conclusions: No clear effect of 3 months daily mobile phone delivered training instructions was detected on body composition, cardiovascular biochemical risk factors or self-perceived health. Further research is needed to evaluate secondary prevention efforts in larger populations after recent stroke.Trial registration number: NCT02902367.
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