Implications for Age and Sex Differences on Anti-Hyperglycemic Therapy Exposure and Incidence of Newly Diagnosed Multiple Sclerosis in Propensity Score Matched Type 2 Diabetics
Gregory Branigan1, Georgina Torrandell Haro1, Francesca Vitali1, Roberta Brinton1, Kathleen Rodgers1
1Center for Innovation in Brain Science, University of Arizona
Objective:
To determine whether exposure to anti-hyperglycemic medications (A-HgM) is associated with risk of Multiple Sclerosis (MS)
Background:
MS is an autoimmune-mediated neurological disorder that affects the central nervous system and leads to severe physical and cognitive disability. There is mounting evidence linking metabolic disorders and MS with unclear impact of therapeutics used to treat type-2 diabetes mellitus (T2D) on the incidence of MS.
Design/Methods:
This retrospective cohort study used the Mariner claims dataset. Patients were required to be actively enrolled in Mariner claims records for six months prior and at least three years after the diagnosis of T2D without a history of previous neurodegenerative disease including MS. Patient records were surveyed for a diagnosis of MS starting 12 months post T2D diagnosis. Survival analysis was used to determine the association between A-HgM exposure and diagnosis of MS with subgroup analysis for the impact of age and sex on risk. A propensity score approach was used to minimize measured and unmeasured selection bias. The analyses were conducted between January 1st and April 28th, 2021.
Results:
In T2D patients younger than 45, A-HgM exposure was associated with a reduced risk of developing MS (RR:0.22, 95%CI:0.17-0.29, p-value<0.001). In contrast, A-HgM exposure in patients older than 45 was associated with an increased risk of MS with women exhibiting greater risk (RR1.53, 95%CI1.39-1.69, p<.001) than men (RR:1.17, 95%CI:1.01-1.37, p=0·04). Patients who developed MS had a higher incidence of baseline co-morbidities. Mean follow-up was 6.2 years with standard deviation of 1.8 years.
Conclusions:
A-HgM exposure in patients with T2D was associated with reduced risk of MS in patients younger than 45 whereas in patients older then 45, exposure to A-HgM was associated with an increased risk of MS particularly in women. These findings represent a call to investigate the interplay between the endocrine, immune and nervous systems in multiple sclerosis.