Could it be that newly diagnosed myeloma patients might benefit and live longer if prescribed the diabetes drug, metformin? Possibly relapsed patients, too? Here is the second installment of Danny Parker’s series:
Metformin, Myeloma and Type 2 Diabetes
For a number of years the evidence has been increasing that there is something about the diabetes drug metformin that seems to help reduce the progression of monoclonal gammopathy of unexplained significance (MGUS) to myeloma. A recent, large and very carefully executed study by Chang et al. (2015) provides compelling evidence that MGUS patients taking metformin experience a lower risk of developing multiple myeloma over time:
And why is that?
Beyond studies of MGUS, for some time we have known that myeloma patients with type 2 diabetes, suffer a shorter overall survival than non-diabetic patients. Research suggests that Insulin-like growth factor-1 (IGF-1), signaling underlies the promoting effect of type 2 diabetes on cancer growth rates. Indeed, this specific pathway has been identified in multiple myeloma pathogenesis in the bone marrow microenvironment (Menu et al., 2009)
Over time the relationship of diabetes and myeloma prognosis has been refined. For instance, a retrospective evaluation of 1240 myeloma patients by Wu et al. (2014), found that the average survival for myeloma patients with diabetes was only 5.5 years as opposed to 8.2 years for non-diabetic patients. Also, the same patients were found to have significantly different rates of achieved remission during myeloma induction therapy. Diabetes patients failed more often to reach CR during induction with or without stem cell transplant.
As myeloma patients often take corticosteroidssuch as Dexamethasone for treatment of the disease, the study found that patients with steroid induced diabetes (SID)—a real risk of steroid treatment—in particular experienced worse survival. Although steroid induced diabetes often ends after treatment, if treatment extends over a long period, the diabetes can become chronic and thus is a real risk for myeloma patients.
Interestingly, this same study also found that within myeloma patients with diabetes, those that were treated with metformin had a statistically significant longer survival than those treated with insulin or similar analogues.
Within the investigation, this beneficial impact of metformin pharmacology remained significant even after controlling for statistical hazards (comorbidities and statistical artifacts of retrospective evaluation such as immortal time bias). While the association of metformin use with better outcomes appeared undeniable within the group of diabetic myeloma patients, no causal relationship can be established from the type of retrospective epidemiological data presented. That important question can only be answered by randomized clinical trials.
But the fact remains that even though a chain of cohort correlation studies—and not definitive– not only has metformin use been associated with longer survival for diabetic patients suffering multiple myeloma, but also for retrospective studies of patients with pancreatic, prostate and HER2+ type breast cancer have shown improved prognosis as well.
Why would metformin have such potential activity relative to cancer?
Laboratory studies, such as those above by Feng et al. (2011), have shown that glucose can promote cancer cell growth rates. This investigation also suggested that glucose can contribute to plasma cell development of resistance to chemotherapy, whereas metformin suppressed cancer cell growth and can even induced apoptosis—killed cancer cells.
We’ll get to that next time. Meanwhile, it is still beautiful autumn in many parts of the U.S.
Remember my recommendation to walk? Did you know just a short walk drops your blood glucose after a meal?
The world is waiting just outside the door.
Thanks, Danny! I’m learning so much about dexamethasone. Doctors admitted that deterioration of my right hip joint was a result of long term dex use. If you recall, I needed a hip replacement. Some have eye problems. Others muscle wasting. Still others retain a lot of water and blow up like a puffer fish. I knew using dex could cause blood sugar complications, but I wasn’t aware of steroid induced diabetes.
Watch for Danny’s next post Monday.
Feel good and keep smiling! Pat