“In patients with rheumatoid arthritis, use of hydroxychloroquine may reduce the risk of developing diabetes by 53%. Given the favorable safety profile and low cost of this generic medication, these findings may have implications for the use of hydroxychloroquine for prevention of diabetes in other high risk groups,” said lead investigator Androniki Bili, MD, MPH, of the Geisinger Medical Center in Danville, Pennsylvania.
HCQ cuts diabetes risk by over 50% in Pennsylvania study
In the first RA analysis Androniki Bili, MD, and colleagues from the Geisinger Medical Center and the University of Pittsburgh used their health system Electronic Health Records (EHR - Epic) database with physician-coded diagnoses and laboratory measures to determine new cases of diabetes mellitus (DM), defined as either CD-9 250 (diabetes) or random serum glucose ≥200 mg/dL or hemoglobin A1c ≥7 or hypoglycemic drug use. Patients were stratified by ever (n = 525) and never (n = 1299) use of HCQ. Mean follow-up was done at 36.2 and 36.8 months, respectively.
Rates for new cases of DM were 17.2 per 1000 patient-years in those who had ever used HCQ vs 33.8 per 1000 patient-years in never users (P = .01.) The hazard ratio (HR), adjusted for gender, age, body mass index, positive rheumatoid factor, and anti-CCP, use of steroids, methotrexate and anti-tumor necrosis factor drugs, was 0.47 (95% confidence interval [CI] 0.26-0.82, P = .008).
The investigators concluded, “Use of HCQ in RA patients in our health system was associated with 53% reduction in risk of DM. Incidence rates of DM in our population are higher than reported elsewhere likely due to the broad definition of DM and high mean BMI in our patients. Duration of HCQ use did not affect risk, perhaps due to the short observation period. These results verify and strengthen the protective association between HCQ use and incident DM by using physician diagnoses and laboratory measures. Given the relative safety and low cost of this generic drug, HCQ may be useful in the prevention and treatment of DM in the general population.”
...and by 33% in study of Medicare data
Daniel H. Solomon, MD, and colleagues from Brigham & Women’s Hospital in Boston, Massachusetts, reached similar conclusions. They used Medicare data from 2 states to determine the risk of incident diabetes among over 25,000 older adults with RA, comparing the relative risks for HCQ, other DMARDs, and oral steroids. All patients had been dispensed at least one DMARD or oral steroid. The primary outcome was new diagnosis of diabetes or new use of a diabetes-specific medication.
Total follow-up time was of 5898 person-years. Overall, the incidence rate for diabetes was 10.9 per 100 person-years. “Compared with [methotrexate] MTX monotherapy, HCQ monotherapy was associated with a 33% reduction in the risk of diabetes (HR 0.66, 95% CI 0.45-0.98). This protective effect was diminished for HCQ with oral steroids (HR 0.93, 95% CI 0.61-1.45). Monotherapy with oral steroids was associated with a dose-dependent increase in diabetes risk (low dose HR 1.44, 95% CI 1.10-1.89; high dose HR 2.21, 95% CI 1.63-2.99),” Dr. Solomon reported.
These researchers joined Bili et al in calling for randomized controlled trials of HCQ as a potential antidiabetic agent.
Table 1: Risk of Renal Disease in Lupus Patients Taking HCQ
| Variables | HR | 95% CI | P-value |
| Age, years | 0.97 | 0.94-0.99 | .0142 |
| Ethnicity* | |||
| Texan Hispanic | 1.90 | 1.11-3.40 | .0207 |
| Manifestations (per ACR criteria) | |||
| Photosensitivity | 0.54 | 0.30-0.95 | .0333 |
| Malar rash | 0.59 | 0.33-1.05 | .0714 |
| Renal disease | 5.75 | 2.76-11.97 | <.0001 |
| SLAM-R1 | 1.10 | 1.05-1.14 | <.0001 |
| HLA-DRB1*1503 | 1.80 | 0.96-3.38 | .0672 |
| Medications | |||
| Hydroxychloroquine | 0.31 | 0.17-0.57 | .0002 |
*Caucasians are the reference group; †as per the corresponding domain of the weighted Systemic Lupus Activity Measure-Revised.
Source: Pons-Estel GJ, et al.3
Not good just for the pancreas, also for the kidneys
Meanwhile, Guillermo J. Pons-Estel, MD, reported that HCQ is so effective at preventing lupus-related kidney problems that it should be considered for inclusion as a routine part of lupus care.
“Our data strongly suggest that if renal damage is to be prevented, HCQ should be prescribed to all lupus patients early in the course of the disease,” said Dr. Pons-Estel, of the University of Alabama at Birmingham.
This study used data for SLE patients (≥4 ACR criteria) from a US multiethnic cohort of African Americans, Hispanics, or Caucasians, age ≥16 years, disease duration ≤5 years at baseline. The investigators defined renal damage using the SLICC damage index (SDI): glomerular filtration rate <50%, 24 hours protein ≥3.5 g and ESRD. The study included only patients with new-onset.
Dr. Pons-Estel reported data for 506 HCQ-takers and 76 nontakers. Multivariate analysis showed that HCQ reduced the risk of renal disease by nearly 70% in these lupus patients with disease duration <5 years [Table].
References
1. Bili A, Newman ED, Kirchner HL, et al. Hydroxychloroquine use reduces risk of diabetes in rheumatoid arthritis patients. Presented at: American College of Rheumatology 2008 meeting; San Francisco, California; October 28, 2008. Presentation 780.
2. Solomon DH, Mogun H, Schneeweiss S, et al. Hydroxychloroquine is associated with a reduced risk of diabetes among older adults with rheumatoid arthritis. Presented at: American College of Rheumatology 2008 meeting; San Francisco, California; October 26, 2008. Presentation 275.
3. Pons-Estel GJ, Danila M, McGwin G, et al. Protective effect of hydroxychloroquine (HCQ) on renal damage in patients with systemic lupus erythematosus (SLE): data from a multiethnic cohort. Presented at: American College of Rheumatology 2008 meeting; San Francisco, California; October 29, 2008. Presentation 2061.