Exenatide

In this double-blind, placebo-controlled trial, 62 patients with moderate Parkinson's disease were randomised to subcutaneous exenatide 2 mg once weekly or placebo for 48 weeks, followed by a 12-week washout. The primary endpoint, the adjusted difference in practically defined off-medication MDS-UPDRS Part 3 motor score at 60 weeks, favoured exenatide by 3.5 points (95% CI -6.7 to -0.3; p=0.0318), with the exenatide group showing a +1.0-point improvement versus a -2.1-point decline on placebo. Because the motor advantage persisted after the 12-week washout, when exenatide would have been cleared, the authors raised the possibility of a disease-modifying rather than purely symptomatic effect, though they cautioned this required confirmation.

Researchers tested a diabetes drug, exenatide, given as a weekly injection, in 62 people with Parkinson's disease over roughly a year. People on exenatide had modestly better movement scores than those on dummy injections, and the benefit lasted even after they stopped the drug for 12 weeks. This hinted the drug might slow the disease itself rather than just mask symptoms, but larger studies were needed to be sure.

This single-blind, controlled proof-of-concept study assigned 45 patients with moderate Parkinson's disease to either exenatide 5 microg twice daily (later 10 microg) subcutaneously for 12 months or to act as controls, all continuing conventional therapy. Exenatide-treated patients showed a mean improvement of 2.7 points on the MDS-UPDRS at 12 months versus a mean decline of 2.2 points in controls (p=0.037), with parallel advantages on cognitive testing (Mattis Dementia Rating Scale). The benefits, though the trial was open-label and small, provided the first clinical signal supporting the neuroprotective/neurorestorative effects of GLP-1 receptor agonism observed in preclinical models and motivated the subsequent double-blind trial.

This early study gave exenatide to 45 people with Parkinson's disease for a year and compared them with untreated patients. Those on the drug improved slightly on movement and thinking tests, while the comparison group got worse. Because it was a small, non-blinded study the findings were preliminary, but they were encouraging enough to justify a rigorous follow-up trial.

This triple-blind, placebo-controlled 30-week trial randomised 336 patients with type 2 diabetes inadequately controlled on metformin to placebo or exenatide 5 or 10 microg twice daily. Exenatide 10 microg reduced HbA1c by 0.78% versus placebo (placebo essentially unchanged), and 46% of the high-dose group reached HbA1c <=7% versus 13% on placebo. Exenatide also produced dose-dependent, progressive weight loss (approximately 2.8 kg with the 10 microg dose) with no increase in hypoglycaemia; mild-to-moderate nausea was the most common adverse effect.

In people with type 2 diabetes whose blood sugar was not well controlled by metformin alone, adding twice-daily exenatide injections meaningfully lowered long-term blood sugar (HbA1c) compared with placebo. Patients also lost weight rather than gaining it, which is unusual for diabetes drugs, and did not have more episodes of dangerously low blood sugar. The main side effect was mild-to-moderate nausea.