Type 2 diabetes is the most common form of the disease, affecting 90 to 95 percent of patients with diabetes, or about 29.1 million people in the United States.
In an effort to address this national health concern, the American College of Physicians (ACP) recently released updated guidance on oral pharmacologic treatment of type 2 diabetes,(annals.org) which the AAFP has endorsed.
In its evidence-based clinical practice guideline published online Jan. 3 by the Annals of Internal Medicine, the ACP recommended physicians prescribe metformin to patients with type 2 diabetes when medication is needed to improve glycemic control.
The guideline further noted that if an additional oral medication is needed to reduce hyperglycemia, physicians may consider adding a sulfonylurea, thiazolidinedione, sodium–glucose cotransporter-2 (SGLT-2) inhibitor or dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin.
- On Jan. 3, the American College of Physicians (ACP) released an evidence-based clinical practice guideline on oral pharmacologic treatment of type 2 diabetes, which the AAFP has endorsed.
- In its guideline, which was published in Annals of Internal Medicine, the ACP recommended physicians prescribe metformin to patients with type 2 diabetes when medication is needed to improve glycemic control.
- If an additional oral medication is needed to reduce hyperglycemia, the ACP recommended physicians consider adding a sulfonylurea, thiazolidinedione, sodium--glucose cotransporter-2 inhibitor or dipeptidyl peptidase-4 inhibitor to metformin.
This update of the ACP's 2012 guideline utilized data from a number of new studies that evaluated medications for this disease, including several newly FDA-approved agents.
According to the ACP Clinical Guidelines Committee, the strong recommendation to prescribe metformin as first-line therapy to lower high blood sugar was based on moderate-quality evidence.
"Metformin, unless contraindicated, is an effective treatment strategy because it has better effectiveness, is associated with fewer adverse effects and is cheaper than most other oral medications," said ACP President Nitin Damle, M.D., M.S., in a news release.(www.acponline.org) "The escalating rates of obesity in the U.S. are increasing the incidence and prevalence of diabetes substantially. Metformin has the added benefit of being associated with weight loss."
Metformin also beats out sulfonylurea monotherapy when it comes to cardiovascular mortality, according to the guideline.
It should be noted that the FDA has stated that metformin is contraindicated in patients with decreased tissue perfusion or hemodynamic instability, advanced liver disease, alcohol abuse, acute unstable congestive heart failure, or any condition that might lead to lactic acidosis.
"However," said the guideline, "the FDA recently concluded that metformin is safe in patients with mild kidney impairment and in some patients with moderate kidney impairment (but is contraindicated in those with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2)."
Regarding its other recommendation to add a second oral medication for some patients, the ACP said physicians should select any such drug based on a discussion with patients.
"Adding a second medication to metformin may provide additional benefits," Damle said in the release. "However, the increased cost may not always support the added benefit, particularly for the more expensive, newer medications. The ACP recommends that clinicians and patients discuss the benefits, adverse effects and costs of additional medications."
Although the evidence reviewed showed that combination therapies with metformin were more effective than metformin monotherapy in reducing hemoglobin A1c (HbA1c) levels, weight and blood pressure in patients with type 2 diabetes, the data could not support making this a strong recommendation.
"This recommendation is graded as weak because of the fine balance between benefits and harms for the various drug combinations," said the guideline.
The ACP also noted that its evidence review didn't include therapies that combined more than two medications and that combination therapies were associated with an increased risk for adverse effects compared with monotherapy.
Further Guideline Details
The updated ACP guideline was based on a systematic review of randomized controlled trials and observational studies published through December 2015 on the comparative effectiveness of metformin, thiazolidinediones, sulfonylureas, DPP-4 inhibitors and SGLT-2 inhibitors for type 2 diabetes.
The guideline group assessed study quality, extracted data and summarized results based on the totality of evidence identified by using several databases. Outcomes evaluated were
- the intermediate outcomes HbA1c, weight, systolic blood pressure and heart rate;
- all-cause mortality;
- cardiovascular and cerebrovascular morbidity and mortality;
- retinopathy, nephropathy and neuropathy;
- and harms.
Guideline committee members used the ACP's guideline grading system, which is adapted from the system developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) working group,(www.gradeworkinggroup.org) to indicate the quality of evidence assessed and the strength of each guideline recommendation; evidence gaps also were identified.
Among those gaps, said the guideline's authors, was a lack of evidence to evaluate clinical outcomes, including mortality, cardiovascular morbidity, and micro- or macrovascular outcomes, for most drugs and drug comparisons.
In addition, said the authors, "The evidence review did not address whether patients who are already taking sulfonylureas and have stable HbA1c levels should switch to another medication. No data exist regarding the best time to add oral therapies to lifestyle modifications."
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