Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus.

BACKGROUND: It is unclear whether patients with type 2 diabetes who have poor glycaemic control despite maximal oral hypoglycaemic agents (OHAs) should be commenced on insulin as monotherapy, or insulin combined with oral hypoglycaemic agents (insulin-OHA combination therapy).

OBJECTIVES: To assess the effects of insulin monotherapy versus insulin-OHA combinations therapy.

SEARCH STRATEGY: Eligible studies were identified by searching MEDLINE, EMBASE, and The Cochrane Library. Date of last search: May 2004.

SELECTION CRITERIA: Randomised controlled trials (RCTs) with 2 months minimum follow-up duration comparing insulin monotherapy (all schemes) with insulin-OHA combination therapy.

DATA COLLECTION AND ANALYSIS: Data extraction and assessment of study quality were undertaken by three reviewers in pairs.

MAIN RESULTS: Twenty RCTs (mean trial duration 10 months) including 1,811 participants, with mean age 59.8 years and mean known duration of diabetes 9.6 years. Overall, study methodological quality was low. Twenty-eight comparisons in 20 RCTs were ordered according to clinical considerations. No studies assessed diabetes-related morbidity, mortality or total mortality. From 13 studies (21 comparisons), sufficient data were extracted to calculate pooled effects on glycaemic control. Insulin-OHA combination therapy had statistically significant benefits on glycaemic control over insulin monotherapy only when the latter was applied as a once-daily injection of NPH insulin. Conversely, twice-daily insulin monotherapy (NPH or mixed insulin) provided superior glycaemic control to insulin-OHA combination therapy regimens where insulin was administered as a single morning injection. In more conventional comparisons, regimens utilising OHAs with bedtime NPH insulin provided comparable glycaemic control to insulin monotherapy (administered as twice daily, or multiple daily injections). Overall, insulin-OHA combination therapy was associated with a 43% relative reduction in total daily insulin requirement compared to insulin monotherapy. Of the 14 studies (22 comparisons) reporting hypoglycaemia, 13 demonstrated no significant difference in the frequency of symptomatic or biochemical hypoglycaemia between insulin and combination therapy regimens. No significant differences in quality of life related issues were detected. Combination therapy with bedtime NPH insulin resulted in statistically significantly less weight gain compared to insulin monotherapy, provided metformin was used +/-sulphonylurea. In all other comparisons no significant differences with respect to weight gain were detected.

REVIEWERS' CONCLUSIONS: Bedtime NPH insulin combined with oral hypoglycaemic agents provides comparable glycaemic control to insulin monotherapy and is associated with less weight gain if metformin is used.