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GUIDELINE WATCH | GENERAL MEDICINE
January 24, 2017
Oral Therapies for Managing Type 2 Diabetes in Adults: An Updated Guideline
Jamaluddin Moloo, MD, MPH Reviewing Fradkin JE and Rodgers GP., Ann Intern Med 2017 Jan 3;
Metformin continues to be recommended as first-line therapy — and it might be prescribed safely to some patients with lower glomerular filtration rates.Sponsoring Organization: American College of Physicians (ACP)
Target Audience: All clinicians
Background
In the U.S., 12 drug classes are approved for treating patients with type 2 diabetes. However, data to guide selection of agents are sparse. To fill this gap, the ACP has updated its 2012 guideline on the comparative effectiveness and safety of oral medications for type 2 diabetes in adults (Ann Intern Med 2012; 156:218). Recommendations are based on a systematic review of randomized trials and observational studies published through December 2015. Evaluated medications were metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase (DPP)-4 inhibitors, and sodium-glucose cotransporter (SGLT)-2 inhibitors.
Key Points
Lowering glycosylated hemoglobin (HbA1c) levels:
– Most drugs were similarly effective in lowering HbA1c levels, although DPP-4 inhibitors were inferior to metformin and sulfonylureas.
– All combination therapies with metformin were superior to metformin monotherapy.
Lowering risk for weight gain:
– Metformin was better for weight reduction than thiazolidinediones, sulfonylureas, or DPP-4 inhibitors.
– Combination therapies with metformin and an SGLT-2 inhibitor or a DPP-4 inhibitor were superior to metformin monotherapy for weight reduction.
– Thiazolidinediones and sulfonylureas were associated with more weight gain.
Harms of antidiabetic therapies:
– Sulfonylureas conferred greater risk for hypoglycemia than did other agents.
– Thiazolidinediones were associated with excess risk for heart failure.
– SGLT-2 inhibitors, alone or combined with metformin, heightened risk for genital mycotic infections compared with other therapies.
– The FDA now considers metformin to be safe for patients with mild renal impairment and for some patients with moderate renal impairment; metformin is contraindicated in patients with glomerular filtration rates ≤30 mL/minute/1.73 m2.
– The DPP-4 inhibitors saxagliptin (Onglyza) and alogliptin (Nesina) might confer risk for heart failure, particularly in patients with cardiac or renal disease.
Data for most intermediate and long-term clinical outcomes remain sparse; however, metformin monotherapy was associated with lower risk for cardiovascular (CV)-related death than was sulfonylurea monotherapy.
Recommendations
Prescribe metformin as first-line therapy (strong recommendation, moderate-quality evidence).
After discussing benefits, adverse effects, and costs with the patient, consider adding a sulfonylurea, a thiazolidinedione, an SGLT-2 inhibitor, or a DPP-4 inhibitor to metformin when glycemic control is inadequate (weak recommendation, moderate-quality evidence).
Comment
This updated guideline consolidates available data on the comparative effectiveness of oral diabetes medications; notably, the guideline does not offer guidance on when initial or add-on therapy is appropriate. Metformin still is recommended as initial pharmacologic therapy, and it now might be prescribed to patients with mild renal insufficiency. For most patients needing add-on therapy for glucose control, this update provides no strong guidance on selecting an optimal agent. In such cases, cost, efficacy, effect on weight, and side effects of the various agents should drive selection — similar to recommendations in the 2017 American Diabetes Association's (ADA's) Standards of Medical Care in Diabetes. However, the ADA also invites clinicians to “consider” prescribing the SGLT-2 inhibitor empagliflozin (Jardiance) for patients with established CV disease, as this drug was associated with lower incidence of adverse CV events in a recently published trial (NEJM JW Gen Med Oct 15 2015 and N Engl J Med 2015; 373:2117). Finally, keep in mind that this ACP guideline does not address use of injected antidiabetes drugs (insulin and glucagon-like peptide-1 receptor agonists).
Editor Disclosures at Time of Publication
Disclosures for Jamaluddin Moloo, MD, MPH at time of publication
Grant / Research support
Colorado Health Foundation
Citation(s):
Qaseem A et al. Oral pharmacologic treatment of type 2 diabetes mellitus: A clinical practice guideline update from the American College of Physicians. Ann Intern Med 2017 Jan 3; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links).
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Fradkin JE and Rodgers GP.Glycemic therapy for type 2 diabetes: Choices expand, data lag behind. Ann Intern Med 2017 Jan 3; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links).
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