Type 2 Diabetes Mellitus: ACP Releases Updated Recommendations for Oral Pharmacologic Treatment
Am Fam Physician. 2017 Oct 1;96(7):472-473.
Key Points for Practice
• Metformin should be the first medication prescribed for diabetes when an oral agent is required.
• Combination treatment is superior to metformin alone for decreasing A1C levels, weight, and blood pressure.
• Medications should be selected based on benefits, possible harms, and cost.
From the AFP Editors
Type 2 diabetes mellitus, which occurs in up to 95% of persons with diabetes, is typically managed with lifestyle modifications (e.g., diet, exercise) and medication (e.g., oral drugs). When weight loss or lifestyle modifications are initially unsuccessful, medication is often prescribed. The American College of Physicians (ACP) previously released guidelines in 2012 regarding the effectiveness and safety of oral pharmacologic treatment for type 2 diabetes; however, new evidence has emerged and new drugs have been approved by the U.S. Food and Drug Administration. For this reason, the ACP has released updated guidelines for the management of type 2 diabetes with oral medication.
If glycemic control needs to be improved with medication in persons with type 2 diabetes, metformin should be prescribed because it can efficiently lower glycemic levels, is linked to losing weight and fewer occurrences of hypoglycemia, and is generally less expensive than other options. It is contraindicated in persons with decreased tissue perfusion, hemodynamic instability, advanced liver disease, alcohol abuse, acute unstable congestive heart failure, and conditions that can result in lactic acidosis.
Because combination treatment has been shown to be superior to metformin alone for decreasing A1C levels, weight, and blood pressure, adding a sulfonylurea, thiazolidinedione, or sodium glucose cotransporter-2 (SGLT-2) or dipeptidyl peptidase-4 (DPP-4) inhibitor can be considered when additional oral treatment is being discussed. The choice of drug should be based on a conversation with the patient about benefits, possible harms, and cost (Table 1).
Comparative Efficacy, Adverse Effects, and Costs for Add-on Oral Therapies to Metformin
|Comparative efficacy vs. other combinations with metformin (quality of evidence)||Comparative harms vs. other combinations with metformin/class adverse effects and FDA warnings||Agents||Fair price for a 60-day supply*||Adverse effects|
Sulfonylurea plus metformin favored for weight vs. TZD plus metformin (moderate)
Higher risk for hypoglycemia than with metformin combinations with TZD, DPP-4 inhibitor, or SGLT-2 inhibitor
Glipizide (Glucotrol), 5 mg
Diarrhea, gas, jitteriness, dizziness, uncontrollable shaking, red or itchy skin, rash, hives, and blisters
Glimepiride (Amaryl), 4 mg
Dizziness and nausea
Glyburide, 5 mg
Nausea and upper abdominal fullness
Glyburide (micronized, 6 mg)
Nausea and upper abdominal fullness
TZD plus metformin favored for short-term CVD mortality (rosiglitazone [Avandia] only) (low) and A1C vs. DPP-4 inhibitor plus metformin (moderate)
TZDs increase risk for congestive heart failure
Pioglitazone (Actos), 30 mg
Headache; muscle, arm, or leg pain; sore throat; and gas
May also be associated with increased risk for fracture or bladder cancer
Rosiglitazone, 2 mg
Headache, runny nose and other cold symptoms, sore throat, and back pain
DPP-4 inhibitor plus metformin favored for long-term all-cause mortality, long-term CVD mortality, and CVD morbidity vs. sulfonylurea plus metformin (low)
FDA warns that sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina) may be associated with potentially severe and disabling joint pain
Alogliptin, 25 mg
Headache, stuffy or runny nose, sore throat, and joint pain
DPP-4 inhibitor plus metformin favored for short-term CVD morbidity vs. pioglitazone plus metformin (low)
Linagliptin, 5 mg
Headache and joint pain
DPP-4 inhibitor plus metformin favored for weight vs. sulfonylurea plus metformin (high) or TZD plus metformin (moderate)
Saxagliptin, 5 mg
Sore throat, headache, and joint pain
Sitagliptin, 100 mg
Stuffy or runny nose, sore throat, headache, diarrhea, nausea, and joint pain
SGLT-2 inhibitor plus metformin favored for CVD mortality (low), A1C (moderate), weight (high), systolic blood pressure (high), and heart rate (moderate) vs. sulfonylurea plus metformin
Higher risk for genital mycotic infection than metformin alone or metformin combined with sulfonylurea or DPP-4 inhibitor
Canagliflozin, 300 mg
Excessive urination, including at night; increased thirst; constipation; and dry mouth
SGLT-2 inhibitor plus metformin favored for weight and systolic blood pressure (moderate) vs. DPP-4 inhibitor plus metformin
FDA warns that canagliflozin (Invokana) may be associated with increased risk of bone fracture and decreased bone mineral density
Dapagliflozin (Farxiga), 10 mg
Excessive urination, including at night,
Coverage of guidelines from other organizations does not imply endorsement by AFP or the AAFP.
This series is coordinated by Sumi Sexton, MD, Associate Deputy Editor.
A collection of Practice Guidelines published in AFP is available at https://www.aafp.org/afp/practguide.
Copyright © 2017 by the American Academy of Family Physicians.
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