Immune modulators are the foundation of treatment in various rheumatologic diseases.1 These medications have proven to be effective for these conditions by altering the immune system, however, they have also been found to produce a variety of endocrine effects in patients as well. These effects include improving pancreatic function and altering erythrocyte survival in both patients with or without diabetes. Because of this, it is important for providers to consider the properties of a particular immune modulator when prescribing treatment as they can greatly affect a patient’s disease management.
Research has shown that rheumatologic disease and diabetes frequently go hand-in-hand.1 It has been found that in patients with type 1 diabetes, there is an increased risk in the development of rheumatoid arthritis. Additionally, patients with rheumatologic disease have increased rates of type 2 diabetes, cardiovascular (CV) risk factors, and CV mortality. Due to their ability to affect both rheumatologic disease as well as diabetes, it is particularly important for providers to know and understand the implications of use of immune-modulating agents in their patients.
A recent analysis by Pilla et al summarized the various effects immune modulators have on patients with diabetes.1 The authors reviewed several studies analyzing the effects these agents have on patients with type 1 and 2 diabetes as well as the effects of these agents on the prevention of diabetes. Several important conclusions were obtained regarding the effects of these agents on patients with type 2 diabetes (Table 1).
Researchers also found that, despite obtaining many important results, many of the immune-modulating agents analyzed did not have any studies completed in patients with type 2 diabetes. Several medications did not have any associated studies in this patient population (Table 2).
In their review, Pilla et al described several studies that demonstrated the antihyperglycemic effect of hydroxychloroquine in patients with type 2 diabetes.1 This antimalarial agent is used first-line for rheumatoid arthritis and systemic lupus erythematosus and is thought to produce its glycemic effect by causing intracellular insulin metabolism changes in peripheral tissues. One randomized controlled trial found that, after 18 months, there was a 1.02% reduction in a patient’s HbA1c measurement when hydroxychloroquine was added to their sulfonylurea therapy (95% CI, 0.24%-1.81%).
Another study found that addition of hydroxychloroquine to insulin therapy significantly reduced a patient’s HbA1c value vs placebo after 6 months. A small retrospective cohort study also discussed in this review found that, compared with methotrexate, hydroxychloroquine had a greater HbA1c reduction from baseline to the lowest value obtained within 12 months of therapy. Hydroxychloroquine also demonstrated its glycemic effect in a noninferiority trial, which found it to have comparable antihyperglycemic efficacy to pioglitazone.
Pilla et al also discussed several important factors that should be considered for patients with rheumatologic disease.1 First, immune-modulating agents that possess antihyperglycemic properties should be utilized in rheumatologic patients with type 2 diabetes or type 2 diabetes risk factors. As seen by the results of various studies discussed in this review, hydroxychloroquine is the preferred agent in patients with difficult-to-control hyperglycemia who require immune-modulating therapy. In addition, based on the evidence of several cohort studies, hydroxychloroquine or a tumor necrosis factor (TNF)-inhibitor may be considered in patients at risk of developing type 2 diabetes.
Another important aspect in the management of a patient with a rheumatologic condition is the appropriate monitoring of that patient after initiation of an immune-modulating agent. Although the glycemic effect of immune modulators is not always immediate, it is important for a patient to be informed of the risk of hypoglycemia as well as the symptoms that may occur prior to the initiation of therapy. The authors also stated that collaboration with the patient, as well as their full care team, is crucial for successful disease management.
Immune modulators are effective medications used in the treatment of several rheumatologic conditions. Many of these agents also produce endocrine effects in patients, which are important for providers to know about and thoroughly understand. Although several studies have been completed, additional analyses regarding the effects of these medications on diabetes and CV outcomes are needed in the future.
Table 1. Effects of Immune-Modulating Agents on Patients with Type 2 Diabetes
|Colchicine||Gout prophylaxis and treatment||
|Dapsone||Off-label for complications of lupus and vasculitides||
|Glucocorticoids||Widely used for their anti-inflammatory and immunosuppressive properties||
|Hydroxychloroquine||RA, SLE, and off-label for a variety of other conditions||
|Methotrexate||RA, JIA, and off-label for a variety of other conditions||
|Sulfasalazine||Mild-moderate RA and JIA, and off-label for a variety of other conditions||
|Tumor Necrosis Factor Inhibitors||RA, psoriatic arthritis, ankylosing spondylitis, JIA, and off-label for a variety of other conditions||
Table 2. Immune Modulators With No Completed Studies in Type 2 Diabetes
- Pilla SJ, Quan AQ, Germain-Lee EL, Hellmann DB, Mathioudakis NN. Immune-modulating therapy for rheumatologic disease: Implications for patients with diabetes. Curr Diab Rep. 2016 Oct 16. doi: 10.1007/s11892-016-0792-9 [Epub ahead of print]
This article originally appeared on MPR