Another way to prevent or treat diabetes?   (May 22, 2008)

There's a medication called salsalate, which is a nonsteroidal anti-inflammatory drug, and has been used for many years to treat arthritis. It is chemically related to aspirin, but unlike aspirin, it hasn't been recommended for prevention of heart attack and stroke.

In a recent publication, Use of Salsalate to Target Inflammation in the Treatment of Insulin Resistance and Type 2 Diabetes, the authors report on three preliminary studies that demonstrate that salsalate may be of benefit by both lowering blood sugar and reducing inflammation. Both high (4.5 g/d) and standard (3.0 g/d) doses of salsalate reduced fasting and postprandial glucose levels after two weeks of treatment.

One of these three studies was published in Diabetes Care in February 2008: Salsalate improves glycemia and inflammatory parameters in obese young adults. This study was pretty rigorous, being a placebo-controlled, double-blind, randomized trial. However, the authors did not look at people with T2DM, but rather at obese folks who had either normal glucose or impaired glucose tolerance (i.e., were at risk of diabetes or had prediabetes). Subjects were less than 30 years old, and obese, with BMI of 30 kg/m2 or greater.

But it was a short study, with only 4 weeks of treatment. And it was a small study: 27 subjects were enrolled, and only twenty participants completed the protocol.
 
What good did the salsalate do? Fasting glucose decreased 13% in the salsalate group compared with the placebo group after 1 month, and the glycemic response to an OGTT improved after salsalate treatment. A1C levels were not measured, but a similar test called glycated albumin was, and the authors found a 17% reduction in the percentage of glycated albumin between salsalate and placebo. Laboratory tests for inflammation also improved. Side effects mentioned in this report included rash (in 3 of 20 subjects), tinnitus, headache, dizziness, and mild elevation of liver enzymes that decreased "spontaneously" (it's unclear if the patients were withdrawn from the drug). No hypoglycemia was noted.

What next? Well, clearly, the study design should be expanded to include people with type 2 diabetes, people who are not dramatically obese, and older folks. And the next time, plan to run the study for many months, and to measure A1C levels. All of which will be more difficult than the present study design, but if the present results are replicated, will be an important finding. I should add that aspirin itself has been shown (in high doses, 4-7 g/day) to improve fasting and postprandial hyperglycemia in patients with diabetes, so it won't be surprising if salsalate also will help. But aspirin in those doses can be pretty toxic, with the potential of life-threatening gastrointestinal bleeding, so it's not recommended for treating or preventing diabetes.

Salsalate for diabetes prevention and/or treatment seems like an interesting idea. Maybe someday we'll recommend routine use of salsalate to prevent diabetes, as well as recommending routine use of aspirin in people with diabetes.