EVIDENCE-BASED ANSWER
Sulfonylureas, metformin, thiazolidinediones, and non-sulfonylurea secretagogues differ little in their ability to decrease glycosylated hemoglobin (HbA1c) levels when used as initial monotherapy for diabetes mellitus type 2 (strength of recommendation [SOR]: A, based on systematic reviews); α-glucosidase inhibitors may also be as effective (SOR: B, based on systematic reviews with inconsistent results). Metformin is generally indicated in obese patients because it improves all-cause mortality and diabetes related outcomes (SOR: B, based on a single high-quality randomized controlled trial [RCT]). Insulin is generally not recommended as an initial agent (SOR: C, expert opinion).
CLINICAL COMMENTARY
Consider the advantages of each class to best meet your patient’s goals
Vincent Lo, MD
San Joaquin Family Medicine Residency, French Camp, Calif
Lifestyle modification is the cornerstone of initial treatment of type 2 diabetes. However, in clinical practice, medications (monotherapy or combination therapy) are often started along with diet and exercise recommendations. Physicians and patients should clearly understand the treatment goals before initiating therapy. Multiple factors often influence treatment goals, such as presence or absence of symptoms, age-related risks from potential hypoglycemia, degree of hyperglycemia, presence of morbidities (renal insufficiency, heart failure, obesity), cost of the medication, as well as patient or physician preferences. Despite their comparable efficacy in the reduction of HbA1c level, each class of oral hypoglycemic medication has a different mechanism of action and adverse side-effect profile. Therefore, physicians must consider the advantages and disadvantages of each class to choose a medication regimen that best meets their patient’s individual treatment goals.
Evidence summary
Oral agents are commonly prescribed for patients with diabetes mellitus type 2 when diet and exercise fail. Options for initiating therapy include sulfonylureas, metformin (Glucophage), α-glucosidase inhibitors, thiazolidinediones, and nonsulfonylurea secretagogues (repaglinide [Prandin] and nateglinide [Starlix]).
A systematic review with 31 placebo-controlled randomized trials (total n=12,185 patients) evaluated changes in HbA1c with monotherapy using 5 different classes of oral agents ( TABLE ).1 Except for the α-glucosidase inhibitor acarbose (Precose), which was less effective, all agents typically reduced HbA1c by 1% to 2%. However, in an additional 19 out of 23 randomized head-to-head studies (total n=5396) included in the same systematic review, all classes showed equal efficacy.
Head-to-head studies are difficult to compare since hypoglycemic medications may reach peak effects at different times. An RCT compared glimepiride (Amaryl), pioglitazone (Actos), and metformin over 12 months of use by 114 patients with diabetes.3 There was no difference among the groups in overall HbA1c reduction. However, glimepiride decreased HbA1c rapidly over 1 month and reached a nadir at 4 months. Pioglitazone did not reduce HbA1c until 6 months and reached its nadir at 7 to 9 months. Metformin produced an intermediate response.