Metformin. That's the word on the street for the best oral diabetes drug for those who are just beginning therapy for the disease, now affirmed by a study in JAMA Internal Medicine. And as Rick and I marvel on PodMed this week, how is it that a comparative effectiveness study of common diabetes medications hasn't been undertaken before? And another marvel: why do so many physicians continue to prescribe medicines other than metformin for initial diabetes therapy, in view of the fact that the American Diabetes Association and a host of other professional and advocacy organizations have been advocating metformin for years? Let's hope this study will convince more of them to adopt evidence-based prescription.
This study looked at 15, 516 patients who were part of the Aetna health insurance network and who began oral glucose lowering therapy from July 1, 2009, through June 30, 2013. Four categories of medication were identified: metformin, a sulfonylurea, a thiazolidinedione, or a dipeptidyl peptidase 4 inhibitor (DPP-4). Review of the charts showed that just under 58% of patients were started on metformin, followed by 23% on the sulfonylureas, just over 13% on the dipetptidyl peptidase 4 inhibitors, and 6.1% on the thiazolidinediones. Out-of-pocket spending for the filling of the initial prescription was significantly higher for DPP-4 inhibitors and thiazolidinediones, the paper states.
What was the likelihood that an additional agent for the management of blood glucose would be required per agent initiated? "In unadjusted analyses, use of medications other than metformin was significantly associated with an increased risk of adding a second oral agent only, insulin only, and a second agent or insulin (P < .001 for all). In propensity score and multivariable-adjusted Cox proportional hazards models, initiation of therapy with sulfonylureas (hazard ratio [HR], 1.68; 95% CI, 1.57-1.79), thiazolidinediones (HR, 1.61; 95% CI, 1.43-1.80), and dipeptidyl peptidase 4 inhibitors (HR, 1.62; 95% CI, 1.47-1.79) was associated with an increased hazard of intensification." Well. Happily, there were no increased risks associated with agents other than metformin, including low blood sugar, ED visits, or in this short term follow-up, cardiovascular events.
Why did so many physicians choose agents other than metformin for initial therapy? In those who have kidney disease metformin is contraindicated, but as Rick quips in the podcast, it's extremely unlikely that 42% of patients in this study had such an issue. He attributes the prescribing behavior to the influence of pharmaceutical companies, both in advertising to physicians and patients, who may come in asking for a certain medication as a result of direct-to-consumer advertising. He also muses that physicians may choose other agents in deference to more up-to-date therapies. To this I must counter that we have abundant clinical experience with metformin and it's very inexpensive. Rick cites other benefits: less weight gain and other side effects. In sum then, we agree with the investigators and guidelines already in place that metformin should be the first line agent of choice in oral management of serum glucose in folks with diabetes, and that's really the evidence based conclusion.
Other topics this week include both an editorial and study from Sierra Leone on Ebola in NEJM, a look at an LDL variant and aortic valve calcification in JAMA, and blood pressure lowering after stroke in the Lancet. Until next week, y'all live well.