An important study called TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) has just been published in the
Annals of Internal Medicine about a drug that's been around forever, salsalate. Several small previous studies have suggested that salsalate (AKA sodium salicylate) might lower blood sugar levels. I wrote about some of these earlier studies a while ago, in an essay titled
Another way to prevent or treat diabetes?
Salsalate 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, isn't likely to cause gastrointestinal bleeding as a side effect. Of importance to us today, salsalate apparently inhibits a substance called NF-kappaB, which is ordinarily activated by obesity and which leads to insulin resistance and increased risk for T2D and cardiovascular disease, which makes it an interesting candidate for a drug to treat diabetes.
The TINSAL-T2D study was done in 128 people with T2D, some of whom were on stable doses of oral antidiabetic drugs and some only on diet-control. The results clearly showed that salsalate lowered blood glucose levels over the 14 weeks of the study. Patients had been randomly assigned to placebo or to varying doses of salsalate (3.0, 3.5, or 4.0 grams/day). Over the 14 weeks, A1C fell in the salsalate-treated groups compared to placebo, as did fasting glucose and another marker of glycemic control, glycated albumen. Improvement in triglyceride levels and adiponectin (a protein involved in glucose and fat metabolism) was also seen.
But there was increase in urinary albumen concentration, which is not a good thing, and might indicate undesirable kidney toxicity. Reported side effects included some typical of salicylates, including heartburn, nausea, vomiting and diarrhea. Tinnitus (ringing in the ears), another known side effect of salicylates, occurred less frequently than anticipated. The drug also caused some hypoglycemia, but only in patients also receiving sulfonylurea treatment.
In summary, salsalate lowered HbA1c levels and improved other markers of glycemic control in patients with type 2 diabetes during this 3-month study, but concern for renal safety were raised. The authors point out that "The number of patients studied and the trial duration were insufficient to warrant recommending the use of salsalate for type 2 diabetes at this time."
Clearly, the TINSAL-T2D study needs to be expanded to include more people, and a longer duration of administration of salsalate, and the authors are doing exactly that: they are currently conducting a follow-up study, which they've nicknamed TINSAL-T2D-II. During this second stage, 282 participants are being randomized to either placebo or salsalate at 3.5 g/d, given for 48 weeks. The primary objective of this second study is to again evaluate the effects of salsalate on glucose control, and to look at how well the drug is tolerated, and to assess "the effects of salsalate on measures of inflammation, the metabolic syndrome, and cardiac risk." So, in a year or two, we'll have lots more information about whether salsalate will become another medication that's recommended for the treatment of type 2 diabetes.