A meta-analysis of head to head studies involving α-glucosidase inhibitors included 8 trials comparing acarbose with sulfonylureas. In pooled results, sulfonylureas trended towards greater HbA1c reduction but did not reach significance (additional HbA1c decrease 0.4%; 95% confidence interval [CI], 0%–0.8%).4
A meta-analysis of head-to-head studies involving metformin showed equal efficacy compared with injected insulin (2 trials, 811 participants), α-glucosidase inhibitors (2 trials, 223 participants), and non-sulfonylurea secretagogues (2 trials, 413 participants).5 In 12 trials with 2067 patients, metformin decreased HbA1c more than sulfonylureas did (standardized mean difference [SMD] –0.14; 95% CI, –0.28 to –0.01). In 3 trials with 246 patients, metformin also produced greater HbA1c decreases than thiazolidinediones (SMD –0.28; 95% CI, –0.52 to –0.03). In the United Kingdom Prospective Diabetes Study (UKPDS), metformin improved diabetes-related outcomes and all-cause mortality in obese patients (relative risk of mortality=0.73; 95% CI, 0.55–0.97; P=.03; number needed to treat [NNT]=19).6
A systematic review with 22 RCTs (total n=7370), ranging in length from 12 weeks to 3 years, compared 2 oral agents with a single oral agent or placebo.1 Combinations of oral agents produced statistically significant additional improvement in HbA1c in 21 of 22 studies. The magnitude of this effect across the studies was on the order of a 1% change in HbA1c, although the data were not subject to a formal meta-analysis.
Inhaled insulin may expand the list of initial therapies for type 2 diabetes. A 12-week manufacturer-sponsored RCT with 134 patients (mean HbA1c=9.5) compared inhaled insulin with rosiglitazone (Avandia).7 More patients using inhaled insulin achieved an HbA1c <8.0 (82.7% vs 58.2%; P=.0003); however, inhaled insulin produced more adverse effects, including cough and hypoglycemia.
TABLE
Oral medications as monotherapy in type 2 diabetes mellitus1,2
| CLASS | DOSING INTERVAL | TYPICAL HBA1C REDUCTION | COST * PER MONTH† | CONTRAINDICATIONS/CAUTIONS |
|---|---|---|---|---|
| Sulfonylureas | 1x daily | 1.4%–1.8% | $ | DKA, caution in hepatic or renal disease |
| Metformin | 1–2x daily | 1.1%–2.0% | $$ | Congestive heart failure, acute or chronic metabolic acidosis, Cr ≥1.5 male, Cr ≥1.4 female, COPD, severe hepatic disease, alcoholism. Use caution in the elderly. |
| α-glucosidase inhibitors | 3x daily | 0.6%–1.0% | $$$ | Cr ≥2.0, abnormal baseline liver function tests, inflammatory bowel disease |
| Thiazolidinediones | 1–2x daily | 1.5%–1.6% | $$$–$$$$ | Class III to IV heart failure, baseline ALT >2.5 |
| Non-sulfonylurea secretagogues | 3x daily | 1.8%–1.9% | $$–$$$ | Caution with liver disease |
| * The “typical” range excludes the studies with the highest and lowest measured effects. | ||||
| † $ = $0 to $25; $$ = $25 to $60; $$$ = $60 to $120; $$$$ = $120 to $180. | ||||
| DKA, diabetic ketoacidosis; Cr, chromium; COPD, chronic obstructive pulmonary disease; ALT, alanine transaminease. | ||||
Recommendations from others
The International Diabetes Federation (IDF) recommends metformin as the initial oral agent unless contraindicated.8 A sulfonylurea is an acceptable alternative in patients who are not overweight. The IDF states that insulin should be added when oral agents fail.
The Institute for Clinical Systems Improvement (ICSI) says that the “single best choice drug for oral agent therapy for type 2 diabetes has not been determined” and must be chosen in the context of age, weight, and other comorbidities.9 The ICSI suggests metformin as an appropriate first agent for obese patients and recommends sulfonylureas or metformin as monotherapy for others because they are both economical and well tolerated. The American Diabetes Association does not specifically recommend a best initial agent or combination of agents for type 2 diabetes.10