News Release 

Metformin-based therapy should be first-line treatment for patients with T2D at low CV risk

Embargoed news from Annals of Internal Medicine

American College of Physicians

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.

1. Metformin-based therapy should be first-line treatment for patients with type 2 diabetes at low cardiovascular risk Abstract: Editorial:

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A comparison of glucose-lowering drugs suggests that metformin-based therapy may be a preferred first-line treatment for drug-naive patients with type 2 diabetes at low cardiovascular risk. There is not enough evidence to reach a conclusion about the optimal initial treatment of drug-naive patients at increased cardiovascular risk. Findings from a systematic review and network meta-analysis are published in Annals of Internal Medicine.

Accumulating evidence shows that antidiabetic drug classes and individual agents differ not only in glycemic efficacy but also in their effect on mortality and vascular end points. This means that clinicians must base their treatment decisions on more than glycemic control. They must also consider individual patient characteristics, such as history of atherosclerotic disease, heart failure, or chronic renal disease. A network meta-analysis that presents the most up-to-date and comprehensive evidence map of the pharmacologic treatment of type 2 diabetes and serves as a bridge between the deluge of clinical research and routine clinical practice.

Researchers from Aristotle University of Thessaloniki in Greece reviewed 453 trials assessing 21 antidiabetic interventions from 9 drug classes to compare benefits and harms of glucose-lowering drugs in adults with type 2 diabetes. The design and rationale of the study were informed by patients' input regarding their views and concerns about the management of the type 2 diabetes and its impact on their lives. Interventions included monotherapies, add-on to metformin-based therapies, and monotherapies versus add-on to metformin therapies. Based on the data, the researchers found no differences between treatments in drug-naive patients at low cardiovascular risk. Insulin regimens and specific glucagon-like peptide-1 receptor agonists (GLP-1 RAs) added to metformin-based background therapy produced the greatest reductions in hemoglobin A1c level. For patients at increased cardiovascular risk receiving metformin-based background therapy, specific GLP-1 RAs and sodium-glucose cotransporter-2 (SGLT-2) inhibitors had a favorable effect on certain cardiovascular outcomes.

These conclusions corroborate and build on the latest treatment recommendations of international scientific organizations by documenting the cardiovascular effects of all available antidiabetic medications and by highlighting differences, not only between drug classes, but also between drugs of the same class. Editorialists from the National Institutes of Health discuss the findings and suggest ways that future clinical trials can best inform individualized care for persons with type 2 diabetes.

Media contacts: For an embargoed PDF please contact Lauren Evans at To speak with the lead author, Apostolos Tsapas, MD, PhD, MSc(Oxon), can be contacted directly at

2. Circumstances around Extreme Risk Protection Orders illustrate importance of such laws for preventing firearm violence



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The circumstances around which Extreme Risk Protection Orders (ERPSs) are filed against individuals in Washington State deemed to be at risk for committing firearm violence against themselves or others illustrate the importance of such laws to potentially save lives. Findings from one of the first statewide studies of ERPOs with detailed information on characteristics of the respondents and circumstances of those orders is published in Annals of Internal Medicine.

In the United States, 74 percent of homicides and 51 percent of suicides involve firearms. Using ERPO laws, petitioners can request restricting firearm access for individuals (respondents) who pose harm to self or others.

Researchers from the University of Washington studied all ERPO respondents in Washington State from December 2016 to May 2019 to characterize respondents and circumstances of ERPOs. Of 237 ERPOs filed during the timeframe, the petitioner indicated that nearly a quarter of respondents had a history of domestic violence perpetration, 62 percent had a history of suicidal ideation or a suicide attempt, and 47 percent had substance use issues. The authors note that a substantial number of guns (641) were removed from the respondents, ranging from handguns to assault rifles and machine guns. In most cases, only one firearm was removed, but the data showed up to 35 guns for one respondent. This is concerning because it's possible that not all guns were reported and removed. According to the researchers, future studies in other states are needed to understand differences and commonalities among states, and ultimately examine the effect of ERPOs on preventing firearm injury and death.

An editorial by authors from John Hopkins School of Public Health discusses these findings and highlights the need for attention to how ERPOs are applied, perceived, and received. They suggest that ERPOs may be especially important right now as new light has been shed on racism and police. Because police are always armed, ERPOs could be employed to prevent dangerous, illegal, and deadly behaviors.

Media contacts: For an embargoed PDF please contact Lauren Evans at To speak with the lead author, Ali Rowhani-Rahbar, MD, MPH, PhD, please contact Sixtine Gurrey

3. Caution should be used when acting on results of genetic testing

Researchers find variances in interpretations of genetic testing for cancer risk genes


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Caution should be used when acting on the results of genetic testing. Researchers at the University of Texas Southwestern Medical Center identified different interpretations for genetic test results for 25 inherited cancer risk genes that would result in actionable recommendations. These findings suggest that a second opinion is warranted when making treatment decisions based on genetic test results. A brief research report is published in Annals of Internal Medicine.

Different genetic test interpretations are an inevitable consequence of the increased number of testing laboratories, incomplete information about the importance of gene variants, the use of subjective guidelines, and the difficulty of functionally testing rare variants for pathogenicity. These differences affect patient management and also can create confusion and mistrust in genetic testing. In addition, differences in interpretation may complicate reimbursement.

Researchers used publicly available data from the Clin-Var database to extract data about the clinical importance of gene variants for the hereditary cancer genes and measure the prevalence of different interpretations for the same genetic variant. They found 40 percent of variants had 2 or more interpretations. Of these, about 2 percent of variants had clinically significant differences in interpretations (benign or uncertain significance versus likely pathogenic). Some types of differences were differences in confidence (likely benign versus benign or likely pathogenic versus pathogenic), and others were differences with modest clinical importance (benign versus uncertain significance). Based on these findings, the researchers suggest that a formally trained, licensed specialist in genetics review the patient's clinical history, the genetic test results, and the different interpretations and then write a report of the findings with recommendations for management.

Media contacts: For an embargoed PDF please contact Lauren Evans at To speak with the lead author, Theodora S. Ross, MD, PhD, please contact


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