Cochrane Briefs

Am Fam Physician. 2005 Mar 1;71(5):899.

Insulin Monotherapy vs. Combination Therapy

Clinical Question

Are combinations of insulin and oral agents more effective than insulin monotherapy in patients with type 2 diabetes mellitus?

Evidence-Based Answer

NPH insulin and metformin taken at bedtime appears to be the most favorable combination studied, but this conclusion is based on poor-quality, inconsistent studies that measure disease-oriented outcomes. There are no data on the effect of these drug combinations on patient-oriented outcomes.

Practice Pointers

Goudswaard and colleagues identified 20 randomized controlled trials (RCTs) with a total of 1,811 patients. The RCTs included 28 comparisons of insulin monotherapy with a combination of insulin and a sulfonylurea, metformin, or both. About one half of the patients were women. The mean age was 60 years, and patients had type 2 diabetes for a mean of 10 years. None of the studies assessed diabetic complications, diabetes-related mortality, or total mortality. In the United Kingdom Prospective Diabetes Study, treatment of overweight patients with insulin or sulfonylureas had no effect on individual or aggregate microvascular or macrovascular outcomes (36.8 versus 38.9 events per 1,000 patient years).1,2

The identified RCTs were fair quality, with a mean score of 2.8 on a seven-point quality scale. Most did not clearly describe how patients were allocated to treatment groups, and 11 RCTs did not blind patients, physicians, or persons evaluating outcomes. A variety of regimens were compared, and results were combined where appropriate. Differences between insulin monotherapy and combination approaches generally were small and inconsistent. The combination of an oral agent and insulin typically resulted in a slightly lower hemoglobin A1C level (0.1 to 0.4 percent), a difference that is unlikely to be clinically important. Patients taking the combination of insulin and metformin were less likely to gain weight than those taking insulin alone, but this combination was examined only in a single, relatively small RCT. There was no difference between groups in the likelihood of symptomatic hypoglycemia.

Goudswaard AN, et al. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;(4):CD003418.


1. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group [published correction appears in Lancet 1999;354:602]. Lancet. 1998;352:837–53.

2. Shaughnessy AF, Slawson DC. What happened to the valid POEMs? A survey of review articles on the treatment of type 2 diabetes. BMJ. 2003;327:266

Use of Beta Agonists in Preterm Labo

Clinical Question

Do betamimetics (i.e., beta agonists) improve outcomes for women with preterm labor?

Evidence-Based Answer

Treatment with betamimetics decreases the number of women with preterm labor who give birth within 48 hours, but it does not decrease the number of births within seven days. Limited evidence suggests that treatment with beta-mimetics does not decrease perinatal death or morbidity.

Practice Pointers

Betamimetics commonly are used to decrease uterine contractions in women with preterm labor. However, they may cause discomfort and life-threatening adverse effects such as pulmonary edema and hypokalemia. Anotayanonth and colleagues identified 11 randomized controlled trials of betamimetics in 1,332 women with preterm labor.

Compared with placebo, the betamimetic ritodrine significantly decreased the number of women who give birth within 48 hours (23 versus 39 percent; relative risk [RR], 0.63; 95 percent confidence interval [CI], 0.53 to 0.75). This corresponds to a number needed to treat of 6. It also reduced the risk of delivery within seven days. This benefit did not persist after the authors performed a sensitivity analysis with a random-effects model.

Most of the participants were at 32 weeks’ gestation or more. Maternal adverse effects included chest pain, dyspnea, tachycardia, palpitations, tremor, headache, hypokalemia, hyperglycemia, nausea and vomiting, and nasal stuffiness. The RR for cessation of treatment because of adverse events was 11.3 (95 percent CI, 3.8 to 33.5). There was no difference in the rate of perinatal and neonatal deaths. Treatment had no effect on neonatal morbidity such as respiratory distress syndrome, cerebral palsy, and necrotizing enterocolitis. Two trials comparing ritodrine with terbutaline in 183 women found that patients who took terbutaline had a higher incidence of hyperglycemia. There was no difference in maternal or neonatal outcomes.

Although no improvement in infant outcomes was found in this review, most of the trials were done before antenatal corticosteroids were used routinely. Also, most of the trials were done in university hospitals. More studies must be done to determine if a 48-hour delay in delivery to allow for patient transfer and a course of corticosteroids improves outcomes. In the meantime, a short trial of tocolysis for preterm labor is reasonable if corticosteroids or transfer is indicated.

Anotayanonth S, et al. Betamimetics for inhibiting preterm labour. Cochrane Database Syst Rev. 2004;(4):CD004352.


1. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 295: pain relief during labor. Obstet Gynecol. 2004;104:213.

Copyright © 2005 by the American Academy of Family Physicians.
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