Novel combination of orlistat and acarbose promising for effective weight loss among obese adults

In the 6-month randomized trial comprising 156 obese adults, participants who were given the new modified-release combination product of lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose, EMP16, lost ~5% more weight versus the placebo group. In the intervention groups, quality of life improved, and withdrawal due to adverse events was low; there was no occurrence of serious events.

Obesity is a chronic disease in which lifestyle modification is needed along with weight-loss medication. There is limited availability of effective drugs with proven long-term safety compared with other chronic illnesses. Currently, only the assessment of liraglutide and Orlistat has been done for more than two years. Orlistat reversibly inhibits the digestion of dietary lipids in the gastrointestinal (GI) lumen, causing modest weight loss, and it has been used for decades without any serious side effects. Orlistat's attrition and efficacy are comparable to other oral weight-loss products, but its conventional oral dosage forms are associated with frequent GI side effects. In its standard dosage, Orlistat is associated with unfortunate side effects, including increased appetite and accelerated gastric emptying.

In this proof-of-concept trial, Ulf Holmbäck, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden, and colleagues tested a fixed-dose combination of Orlistat and the antidiabetic drug acarbose (Precose) in adults with obesity. EMP16, the novel oral, modified-release formulation, was designed to improve efficacy and tolerability compared to conventional dosage forms.

The researchers evaluated the effect of EMP16 on relative body weight after 26 weeks compared with a placebo.

The treatment period of the randomized, double-blind, placebo-controlled trial was 26 weeks, with a dose escalation of up to 6 weeks. It included adults aged 18 to 75, with BMI ≥30 kg/m2 or ≥28 kg/m2 with risk factors. They were assigned randomly to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The study's primary endpoint was relative weight loss from baseline to week 26, estimated in participants with at least one post-baseline weight measurement.

The study led to the following findings:

• Of 156 randomized participants, 149 comprised the intention-to-treat population.
• The mean 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%) with EMP16-120/40 and −5.42% (−6.60% to −4.24%) with EMP16-150/50.

The researchers conclude that " our trial findings support that orlistat and acarbose can be successfully combined as a promising potential candidate for improved weight management."

Reference:

Holmbäck U, Grudén S, Litorp H, Willhems D, Kuusk S, Alderborn G, Söderhäll A, Forslund A. Effects of a novel weight-loss combination product containing Orlistat and acarbose on obesity: A randomized, placebo-controlled trial. Obesity (Silver Spring). 2022 Sep 19. doi: 10.1002/oby.23557. Epub ahead of print. PMID: 36123783.