SOURCE: Athauda D, Maclagan K, Skene SS, et al. Lancet 2017 Aug 3. pii: S0140-6736(17)31585-4. doi: 10.1016/S0140-6736(17)31585-4. [Epub ahead of print].

Most clinicians are used to thinking about dopamine modulation when considering treatments for Parkinson’s disease. Unfortunately, none of the current treatments can be designated as disease-modifying, even though such treatment provides transient symptomatic relief.

Current use of a glucagon-like peptide-1 receptor agonist (GLP-1RA) is limited to the management of type 2 diabetes. From where did the idea emerge that GLP-1RA might benefit Parkinson’s patients?

The authors of studies about Parkinson’s based on animal models have noted that a GLP-1RA not only crosses the blood-brain barrier, but produces sufficient neuroprotective and neurorestorative effects to improve motor function and memory. Investigators who conducted a subsequent open-label, one-year pilot trial of exenatide in humans with Parkinson’s disease found favorable effects that endured for an additional 12 months post-treatment.

Based on these early successes, Athauda et al performed a randomized, double-blind, placebo-controlled trial of exenatide administered in weekly, subcutaneous, 2 mg doses (n = 62) for 48 weeks added to whatever current regimen study participants were receiving. The primary outcome was the motor performance subscale of a Parkinson’s disease rating scale, measured 12 weeks after discontinuing exenatide treatment.

Motor function improvements were demonstrated in exenatide-treated patients, whereas investigators noted deterioration in placebo patients. Larger, longer-term studies will be needed before GLP-1RA treatment could be confirmed as an appropriate consideration for Parkinson’s patients.