Combining insulin with metformin or insulin secretagogue in nonobese patients (diab2)

[FRSM]

Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial

"...Discussion
Abstract
Introduction
Methods
Results
Discussion
References

Principal findings
In this randomised, double blind study, 101 non-obese patients with type 2 diabetes who had glycaemic failure after four months on oral hypoglycaemic agents combination therapy received metformin plus biphasic insulin aspart 70/30 or repaglinide plus biphasic insulin aspart 70/30 for 12 months. Both treatment groups achieved similar and near optimal glycaemic regulation with similar doses of insulin, which suggests that metformin and repaglinide are equally effective diabetes treatments in such patients. Weight gain, however, seemed less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30.
The incidence of mild symptomatic and major hypoglycaemia was not significantly different between treatments. The rate of major hypoglycaemia was 0.1-0.2 per year, which corresponds to one such episode every five to ten years per patient. The number of non-hypoglycaemia related serious adverse events was low.

We used near maximal daily doses of metformin (2000 mg) and repaglinide (6 mg) and observed a tendency towards lower pre-breakfast and post-breakfast levels of self monitored plasma glucose with insulin plus metformin (p=0.055 and p=0.051, respectively; fig 4). Hence, we cannot exclude the possibility that in our population of non-obese patients with type 2 diabetes, higher doses of metformin and repaglinide would have resulted in notable glycaemic differences between treatment groups.

In contrast to present consensus statements recommending that insulin secretagogues are stopped after initiation of insulin therapy,7 our data suggest a clinically relevant effect of insulin and insulin secretagogues in combination, even in patients with long standing diabetes in whom beta cell failure otherwise could be anticipated (that is, in the present study patients had preserved beta cell function despite approximately 10 years of diabetes). Patients in our study achieved good glycaemic control using a single oral hypoglycaemic agent in combination with insulin therapy. Such therapy could thus be more convenient than two or more oral hypoglycaemic agents in combination with insulin therapy. This suggestion is supported to some degree by the observed low drop out rate and satisfactory compliance....."

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