2 from DGIM co-authors of major metformin review

Sunday, January 8, 2017

Already the newest systematic review from the Durham VA Evidence Synthesis Program boasts an Altmetrics “attention score” of 140 (as of 1/8/17). The paper’s significance is highlighted in 5 news outlets and over 100 tweets and retweets. In addition, the journal itself provided an editorial about the research. Amongst several Duke authors for this publication, two represent DGIM: Dr. Clarissa Diamantidis and senior author, Dr. John Williams.

Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review. Crowley MJ, Diamantidis CJ, McDuffie JR, Cameron CB, Stanifer JW, Mock CK, Wang X, Tang S, Nagi A, Kosinski AS, Williams JW Jr. Ann Intern Med. 2017 Jan 3. doi: 10.7326/M16-1901. [Epub ahead of print] PMID: 28055049

[Editorial: KJ Lipska, MD, MHS, Yale School of Medicine, “Metformin Use in Patients with Historical Contraindications”]

Each year, the VA ESP Center conducts three systematic reviews. This particular study was requested by the VA Guideline Group, one currently involved in updates of the VA/DOD guideline for Patients with Diabetes and the VA Pharmacy Benefits Management Group.

IT tools for research

We further explored with Dr. Williams just how the team worked and the process of reporting such important findings. To begin, we learned their team engaged several information technology tools: Duke Box to store and share documents, the Endnote database for citations, and DistillerSR, a web-based tool customized for systematic reviews to identify relevant studies and abstract data. Distiller allows anyone or everyone on the team to work on the project simultaneously. Teleconferencing/Webex facilitated their team meetings. Williams told us “we had a relatively small team so collaboration was relatively easy. The big challenge is always navigating clinical schedules.”

A key methodology

Systematic review methodology is designed to produce comprehensive, unbiased syntheses of published literature. Probably the best-known organization that conducts these studies internationally is the Cochrane Collaboration. In the US the AHRQ funded Evidence-based Practice Program (we have one at Duke) and the VA Evidence Synthesis Programs are especially well known. The studies use a very structured, protocol-driven process to identify studies and synthesize the data. In this instance, the researchers used meta-analyses, a statistical approach to summarize the effects of metformin on mortality and other important outcomes.

The authors were pleasantly surprised that the journal review took only 4-6 weeks for the initial review. The paper was then accepted within a week of submitting the revised manuscript. For this manuscript the reviewer input covered recommendations about conducting sensitivity analyses to see if the findings were the same under different assumptions (they were) and some suggestions on how to contextualize the results. In general, the Annals of Internal Medicine is not only expeditious, the editors give high quality feedback and timely publication.

Finally, new confidence for candidates to take metformin

According to Dr. Williams, while the team was conducting the study, the FDA changed its guidance for metformin, liberalizing the use in patients with CKD. They did this based largely on safety data. This study supports the FDA changes by adding data on benefit, in addition to safety. The impact will be to extend metformin use to patients who prior to late last year may not have been thought to be good candidates for this treatment.

"This will improve practice!" - Daniella Zipkin, MD

From our DGIM clinicians we heard Dr. Daniella Zipkin express gratitude “for filling a significant knowledge gap in the safety of metformin that will improve practice!"

Kudos to PI, Duke Endocrinologist Dr. Matt Crowley and team

Matt Crowley (PI) is an HSR&D investigator and endocrinologist. He is an Assistant Professor and is supported by a VA Career Development Award. Not all the investigators are HSR&D. There were several Duke nephrologists on the team. This ESP team also includes a national advisory group called a Technical Expert Panel (or TEP) for each of these projects.

What's next?

This ESP team is working on three very interesting reviews this year: the effects of support for family caregivers of patients with PTSD, TBI, or polytrauma; the effects of early palliative care for patients with advanced cancer; and, an evidence map of telehealth programs customized for women.