https://diabetes.acponline.org/archives/2017/01/13/2.htm

ACP releases updated guideline on oral pharmacologic treatment of type 2 diabetes

ACP recommended that clinicians prescribe metformin for type 2 diabetes when pharmacologic therapy is needed to improve glycemic control in a strong recommendation based on moderate-quality evidence.


ACP's updated guideline on oral pharmacologic treatment of type 2 diabetes recommends metformin as a first-line oral agent to improve glycemic control.

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The guideline, which updated the 2012 ACP guideline on the same topic, was based on a systematic review of randomized controlled trials and observational studies that were published through December 2015 and examined the comparative effectiveness of oral medications for type 2 diabetes. The guideline was endorsed by the American Academy of Family Physicians and was published online Jan. 3 by Annals of Internal Medicine.

The review found that while all oral diabetes medications reduced HbA1c levels, dipeptidyl peptidase-4 (DPP-4) inhibitors did not perform as well in this area as metformin and sulfonylureas. Metformin had the most positive effect on weight of all oral diabetes medications besides sodium-glucose cotransporter-2 (SGLT-2) inhibitors. SGLT-2 inhibitors also reduced blood pressure more than metformin did. Reductions in HbA1c, weight, and blood pressure were greater with metformin plus an SGLT-2 inhibitor or DPP-4 inhibitor than with metformin alone.

Compared with sulfonylureas, metformin monotherapy was associated with a lower hypoglycemia risk and associated with lower risk for cardiovascular death. Sulfonylureas were found to increase the risk for hypoglycemia, while thiazolidinediones were found to increase risk for congestive heart failure and SGLT-2 inhibitors were found to increase the risk for genital mycotic infections. Thiazolidinediones and sulfonylureas were associated with weight gain versus metformin, DPP-4 inhibitors, and SGLT-2 inhibitors.

The ACP guideline recommended that clinicians prescribe metformin for type 2 diabetes when pharmacologic therapy is needed to improve glycemic control. This is a strong recommendation based on moderate-quality evidence. The guideline committee noted that the FDA considers metformin contraindicated in patients with decreased tissue perfusion or hemodynamic instability, advanced liver disease, alcohol abuse, acute unstable congestive heart failure, or any condition that could lead to lactic acidosis. However, the committee said, the FDA recently declared metformin safe in patients who have mild kidney impairment and in some with moderate kidney impairment, although it remains contraindicated in those with an estimated glomerular filtration rate below 30 mg/min/1.73 m2.

The ACP guideline recommended that clinicians consider adding a sulfonylurea, a thiazolidinedione, an SGLT-2 inhibitor, or a DPP-4 inhibitor to metformin to improve glycemic control when a second oral therapy is considered. This is a weak recommendation based on moderate-quality evidence. ACP also recommended that clinicians and patients discuss medications' benefits, adverse effects, and costs before making a selection.

An accompanying editorial from the National Institutes of Health noted that there are now 12 classes of FDA-approved drugs available to treat type 2 diabetes, making it a challenge to maintain the appropriate level of glycemic control while considering patients' characteristics and preferences. The editorialists also stressed the lack of “long-term, head-to-head comparator studies of the many available glucose-lowering medications” to help clinicians determine which is best to add to metformin, stating that an in-progress trial from the National Institute of Diabetes and Digestive and Kidney Diseases may help provide further data.