AbstractBackgroundType 2 diabetes and obesity may be inversely associated with amyotrophic lateral sclerosis (ALS), but the evidence is controversial.MethodsUsing Danish, nationwide registries (1980‐2016), we identified patients with a diagnosis of type 2 diabetes (N= 295,653) and patients with a diagnosis of obesity (N= 312,108). Patients were matched (1:3) to persons from the general population on birth year and sex. We computed incidence rates and Cox regression derived hazard ratios (HRs) of a diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, birth year, calendar year, and comorbidities.ResultsWe observed 168 incident cases of ALS (0.7 [95% confidence interval (CI): 0.6–0.8] per 10,000 person‐years) among patients with type 2 diabetes and 859 incident cases of ALS (0.9 [95% CI: 0.9–1.0] per 10,000 person‐years) among matched comparators. The adjusted HR was 0.87 (95% CI: 0.72–1.04). The association was present among men (adjusted HR: 0.78 [95% CI: 0.62–0.99]) but not women (adjusted HR: 1.03 [95% CI: 0.78–1.37]), and among those aged ≥60 years (adjusted HR: 0.75 [95% CI: 0.59–0.96]) but not younger. We observed 111 ALS events (0.4 [95% CI: 0.4–0.5] per 10,000 person‐years) among obesity patients and 431 ALS events (0.5 [95% CI: 0.5–0.6] per 10,000 person‐years) among comparators. The adjusted HR was 0.88 (95% CI: 0.70–1.11).ConclusionsDiagnoses of type 2 diabetes and obesity were associated with a reduced rate of ALS compared with general population comparators, particularly among men and patients aged 60 years or above. However, absolute rate differences were small.