Numerous studies have also described the role of IL-1β in impaired insulin secretion and insulin resistance. These include eight independent clinical trials using three different IL-1 modulators that confirm the important role of IL-1β for glucose metabolism in patients with diabetes. For example, anakinra (an IL-1β antagonist) treatment of patients with prediabetes resulted in improved β-cell secretory function. Later studies demonstrated that anakinra influences insulin secretion and insulin resistance, thereby improving type 2 diabetes pathogenesis. Canikinumab (another IL-1β-specific antibody) was also able to slightly improve insulin secretion rate in a small study of individuals with impaired glucose tolerance or well-controlled type 2 diabetes. A third IL-1 modulator (IL-1β-specific antibody, LY2189102) was able to improve glycated hemoglobin levels, fasting and postprandial glycemia, and inflammatory biomarkers.
Effective Immunomodulatory Drugs
Salsalate inhibits the NF-κB pathway. It is the prodrug form of salicylic acid and is prescribed because it has fewer side effects than sodium salicylate. Seven individual clinical trials have demonstrated that salsalate improves both inflammatory and metabolic markers. Specifically, treatment with salsalate improved glycemia, reduced levels of C-reactive protein and increased adiponectin blood plasma levels in obese and nondiabetic adults as well as adults with diabetes. In some cases, the mechanism of action of an antiinflammatory drug has not yet been fully elucidated. This is the case for diacerein and AC-201. Both of these antiinflammatory drugs have proven effective in patients with type 2 diabetes.
Future of Antiinflammatory Drugs
The cost of treating patients with diabetes is rapidly becoming a global concern. By extension, the cost of any new drug will likely be scrutinized, particularly since type 2 diabetes is a slowly progressing chronic disease. Treatment of diabetes with antiinflammatory drugs also raises numerous questions revolving around the magnitude of effect, as well as long-term safety. In particular, there is concern about the long-term effects of immunomodulatory drugs with long half-lives.
Dr. Donath believes rheumatologists will have an important role in exploring the effect of immunomodulatory drugs on the treatment of type 2 diabetes. “A large number of patients treated by rheumatologists have diabetes alongside with their rheumatoid disease. Some antiinflammatory drugs may improve both conditions. For example, patients with RA and diabetes may benefit for both conditions from a TNF antagonist or patients with gout and diabetes may have optimal treatment with an IL-1 antagonist.”
Can Obesity Be Ignored?
Deborah Jane Wexler, MD, an endocrinologist at Massachusetts General Hospital in Boston, spoke with The Rheumatologist by phone about the review article and the alternative approach to treating diabetes it describes. While agreeing that an antiinflammatory approach to treating diabetes is attractive for many diabetes scientists, she points out, “the problem is that the search for the antiinflammatory silver bullet drug has not been successful.”