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Orlistat-acarbose combination may facilitate weight loss with fewer GI effects vs. orlistat alone
A modified-release fixed-dose formulation of orlistat and acarbose is well tolerated and may be an effective approach for weight loss, according to results of a phase 2a pilot study published in Obesity Science and Practice.
The combination is designed to provide the weight-loss effects of orlistat and to reduce orlistat’s tendency to stimulate appetite with acarbose, according to researchers, who cautioned that prescribing orlistat together with conventional acarbose is not recommended.
“By changing lipid and carbohydrates digestion, the aim was to trigger neuroendocrine feedback signaling systems and thereby affect appetite,” Ulf Holmback, assistant professor in the department of public health and caring sciences, clinical nutrition and metabolism at Uppsala University, and colleagues wrote. “In addition, as glucose metabolism usually is affected in people with obesity and the risk of developing diabetes type 2 is increased, the combination has the additional benefit of the effect of acarbose on the postprandial glucose response.”
Holmback and colleagues conducted a single-center, randomized, controlled, parallel-group, study to compare the effects on appetite and tolerability of orlistat (Xenical, Roche) vs. three doses of a modified-release fixed-dose formulation of orlistat plus acarbose.
For the 2-week study, researchers assigned 16 healthy men (mean age, 40.5 years; mean BMI 34.5 kg/m2; mean waist circumference 119 cm) to receive a daily dose of 60 mg orlistat/20 mg acarbose, 17 men (43.4 years, 34.1 kg/m2, 119 cm) to receive 90 mg of orlistat/30 mg acarbose, 16 men (42.3 years, 34.8 kg/m2, 121 cm) to receive 120 mg of orlistat/40 mg of acarbose, and 17 men (45.5 years, 35.4 kg/m2, 119 cm) to receive conventional orlistat.
Participants took their medication with meals: at breakfast and lunch provided during study visits on days 1 and 14 and with three meals at home on other days and dinner at home on study days as well. Participants reported gastrointestinal symptoms and subjective appetite via questionnaires for 3 days before the study began and then after meals throughout the study. Researchers took blood samples at the beginning, middle and end of the 2 weeks and at a follow-up visit on day 21.
The combination drug groups reported fewer orlistat related adverse effects, such as liquid and oily stools, along with some acarbose-related adverse effects, such as flatulence and gastric distension. More participants in the 90/30 and 120/40 dosage groups reported reduced hunger when compared with the orlistat-alone group.
On days 1 and 14, the highest blood glucose concentrations were significantly lower for the groups receiving any of the orlistat-acarbose combinations vs. conventional orlistat (P .05). The combination groups vs. the orlistat-alone group also had significantly lower mean blood glucose concentrations and lower maximum insulin concentrations at day 1, but not day 14 (P .05). Mean insulin concentrations were similar across groups on both study days.
No differences in reported hunger, feelings of fullness or desire to eat were observed between groups for the 14-day period. Numbers of participants reporting a prespecified decrease from baseline in hunger after lunch and dinner were significantly larger for the combination groups vs. the orlistat-only group.
These findings show it is possible to combine orlistat and acarbose in a modified-release formulation without increasing GI side effects, with additional benefits of decreasing hunger and reducing post-meal glucose concentrations, according to the researchers.
“The effect on hunger, together with the effects on glucose and insulin levels, indicate that the specifically designed release rates of orlistat and acarbose trigger systems involved in appetite regulation,” the researchers wrote. “These preliminary results need to be confirmed in a study of longer duration in a more diverse population where weight loss is the primary outcome.” – by Erin T. Welsh
Disclosures: Holmback reports having equity interests in and serving as a consultant to Empros pharma AB. Please see the full study for other authors’ relevant financial disclosures.