The American College of Physicians (ACP) recently lauded the World Health Organization (WHO) for its efforts in fighting type 2 diabetes, and its new evidence-based guideline on the benefits and harms of medications, intervention costs, and application to resource-poor settings, according to a commentary published in the Annals of Internal Medicine.

But ACP experts also offered treatment recommendations that differed with some of the points made in the WHO’s guideline.

“The [WHO] guideline reinforces several others—including the American College of Physicians guideline—and highlights the importance of lifestyle changes in managing diabetes and the use of metformin as the best first-line pharmacologic therapy for most patients with type 2 diabetes,” wrote authors led by Linda L. Humphrey, MD, MPH, chair of the High Value Care Committee, American College of Physicians, Philadelphia, PA.

In the commentary, ACP experts provided feedback on WHO recommendations of second- and third-line treatments and the differences between WHO and ACP guidelines.

“We consider the nuances of clinical decision making in the face of limited evidence and limited resources,” the authors wrote, “and we describe the WHO guideline’s implications for clinicians in the United States.”

Second-line agents

The WHO guideline recommends sulfonylureas as the optimal second-line agent when metformin fails to attain glycemic targets or in patients in whom metformin is contraindicated. Although sulfonylureas are cheaper and work just as well as newer agents in lowering hemoglobin A1C, the authors raised concerns about the cumulative effects of hypoglycemia, which is a risk of these drugs.

Dr. Humphrey and colleagues pointed out that the WHO prioritized sulfonylureas based on cost and access considerations, which, although important, are less relevant in the United States. In 2017, the ACP recommended that physicians consider the importance of adverse events, such as patient comorbidities, weight gain, and risk of glucose disturbance, when prescribing a sulfonylurea, a thiazolidinedione, an SGLT-2 inhibitor, or a DPP-4 inhibitor as a second-line oral agent.

The ACP experts also bridged additional benefits of drugs when choosing second- and third-line agents when treating type 2 diabetes, a consideration that was acknowledged by the WHO. For instance, the SGLT-2 inhibitors empagliflozin and canagliflozin could decrease cardiovascular events and hospitalizations for heart failure in patients at high risk for heart disease, as well as reducing blood pressure, decreasing renal events, and slowing the clinical course of kidney disease.

“We look forward to more research in these important areas and believe that guideline recommendations will change in the coming years as more experience with these medications and longer-term data accrue,” the authors wrote.

Fasting blood glucose levels

Importantly, the ACP experts pointed out that WHO guidance suggests a fasting blood glucose of < 126 mg/dL, which once again is likely rooted in the WHO’s concerns about costs in resource-poor practice settings. Nonetheless, previous research has not supported the targeting of fasting blood glucose in clinical decision-making, and the majority of other diabetes guidelines focus on hemoglobin A1C-based clinical calculus.

“In summary, although the WHO and ACP guidelines are similar in many respects, differences do emerge,” wrote the authors. “The ACP recommends that clinicians and patients discuss benefits, adverse effects, and costs when choosing among second-line therapy options, including sulfonylureas, thiazolidinediones, SGLT-2 inhibitors, and DPP-4 inhibitors.”

This story is contributed by Naveed Saleh and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.