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Am Fam Physician. 2022;106(1):61-69

Published online June 1, 2022.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: Dr. Ebell is cofounder and editor-in-chief of Essential Evidence Plus; see Editor’s Note. Dr. Grad has no relevant financial relationships.

This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men; rectal bleeding in women; and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.

Annually for 23 years, a team of clinicians has systematically reviewed English-language medical journals to identify the research most likely to change and improve primary care. The team includes experts in family medicine, pharmacology, hospital medicine, and women’s health.1,2

The goal of this process is to identify POEMs (patient-oriented evidence that matters). A POEM must report at least one patient-oriented outcome, such as improvement in symptoms, morbidity, or mortality. It should also be free of important methodologic bias, making the results valid and trustworthy. Finally, if the results were applied in practice, some physicians would change what they do by adopting a new practice or discontinuing an old one shown to be ineffective or harmful. Adopting POEMs in clinical practice should improve patient outcomes. Of more than 20,000 research studies published in 2021 in the journals reviewed by the POEMs team, only 260 met criteria for validity, relevance, and practice change. These POEMs are emailed daily to subscribers of Essential Evidence Plus (Wiley-Blackwell, Inc.).

The Canadian Medical Association purchases a POEMs subscription for its members, many of whom receive the daily POEM. As these physicians read each POEM, they can rate it using a validated questionnaire. This process is called the Information Assessment Method ( POEM ratings address the domains of clinical relevance, cognitive impact, use in practice, and expected health benefits if that POEM is applied to a specific patient.2,3 In 2021, each of the 260 daily POEMs were rated by an average of 1,189 physicians.

In this article, the 11th installment of our annual series (, we present the 20 most clinically relevant POEMs of 2021 as determined by Canadian Medical Association members. Looking beyond COVID-19, our patients continue to face the usual (and unusual) health problems of everyday life. Thus, we summarize the clinical questions and bottom-line answers for research studies about a variety of topics that were identified as top 20 POEMs, followed by a brief discussion. This set of 20 POEMs includes the most relevant practice guidelines of the year. The full POEMs are available online at

The five most highly rated POEMs in 2021, and eight of the top 15, were about the COVID-19 vaccines and their effectiveness in different populations. Because of the emergence of variants and widespread endorsement of the vaccine by family physicians, these POEMs are not as likely to lead to practice changes as they were when originally published. One additional COVID-19 POEM reported the incidence of myocarditis following vaccination with the Pfizer BioNTech and Moderna mRNA vaccines in U.S. military personnel. The incidence of approximately 4 more cases than expected per 100,000 patients is significantly lower than the more than 300 per 100,000 patients seen among those with SARS-CoV-2 infection.4 The rest of this article includes POEMs not related to the COVID-19 pandemic.

Type 2 Diabetes Mellitus

The first three POEMs in this category are about the management of type 2 diabetes (Table 1).58 The first study identified 2,482 adults with a mean age of 75 years who had prediabetes (defined as an A1C level between 5.7% and 6.4%, a fasting glucose level between 100 and 125 mg per dL [5.55 and 6.94 mmol per L], or both).5 Over an average of 6.5 years, only 8% to 9% of patients progressed to diabetes, many regressed to normoglycemia, and the remainder stayed at prediabetic levels. These results will help reassure physicians and avoid overtreatment of older patients with prediabetes. Of note, the U.S. Preventive Services Task Force does not recommend screening for prediabetes or type 2 diabetes beyond 70 years of age.9

Clinical questionBottom-line answer
1. What is the likelihood that older adults with prediabetes will develop diabetes mellitus over an average of 6.5 years?5 More than 90% of older adults with prediabetes will not develop diabetes.
Prediabetes is a risk factor for a risk factor. Or not. Older patients generally will not progress to diabetes over 6.5 years. They will stay at prediabetic A1C levels or revert to normal levels. In other words, if a patient makes it to their mid-70s without a diagnosis of diabetes, it is unlikely to occur.
2. What are the risks of overtreatment in patients 70 years or older with type 2 diabetes?6 Tight control of diabetes leads to unnecessary hospitalizations in older patients. Sulfonylureas should be used with caution.
In older patients with type 2 diabetes, a consistent A1C level of less than 7% is associated with at least one hospitalization for the treatment of hypoglycemia. Treatment with a sulfonylurea or insulin magnifies the risk.
3. Do SGLT-2 inhibitors or GLP-1 receptor agonists improve patient-oriented outcomes in patients with type 2 diabetes?7 Both SGLT-2 inhibitors and GLP-1 receptor agonists reduce all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, and kidney failure in patients with diabetes.
SGLT-2 inhibitors, the diabetes medications ending inflozin (e.g., dapagliflozin [Farxiga]), and GLP-1 receptor agonists, the medications ending intide (e.g., dulaglutide [Trulicity]), decrease cardiovascular and renal outcomes to a greater extent than placebo or other treatments. They should be considered in addition to metformin and perhaps another glucose-lowering therapy for most patients with type 2 diabetes.
4. What effect do SGLT-2 inhibitors have on mortality, cardiovascular outcomes, and renal outcomes in patients with and without type 2 diabetes, heart failure, or kidney disease?8 Even in patients without diabetes, SGLT-2 inhibitors reduce all-cause and cardiovascular mortality and the progression of renal disease.
SGLT-2 inhibitors reduce all-cause and cardiovascular mortality regardless of the presence of type 2 diabetes, heart failure, or chronic kidney disease. Similar mortality reduction occurs in patients with diabetes regardless of comorbid heart failure and in patients with heart failure regardless of the presence of diabetes. SGLT-2 inhibitors also reduce the progression of renal disease in all patients.

A study in the United Kingdom identified 6,288 people 70 years and older with type 2 diabetes and three consecutive A1C measurements of less than 7%.6 Approximately 90% were taking a sulfonylurea. Compared with a similar group of people with type 2 diabetes who did not have A1C levels of less than 7% and were not taking a sulfonylurea, those with tight control were 2.5 times more likely to be hospitalized for severe hypoglycemia, with a 1 in 7 risk of hospitalization over 10 years. Use of a sulfonylurea or insulin was associated with severe hypoglycemia and death. A more relaxed A1C target of 7.0% to 8.0% is more appropriate, especially for older patients, and sulfonylureas should be used with caution.

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