Published 9 November 2009, doi:10.1136/bmj.b4324
Cite this as: BMJ 2009;339:b4324

Research

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

¹ Steno Diabetes Center, Gentofte, Denmark, ² Institute of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark, ³ Faculty of Health Sciences, University of Århus, Århus, Denmark, ⁴ Hagedorn Research Institute, Gentofte, ⁵ Rigshospitalet, Department of Medical Endocrinology, University of Copenhagen, ⁶ University of Lund, Department of Endocrinology, Malmö, Sweden

Objectives To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes.

Design Randomised, double blind, double dummy, parallel trial.

Setting Secondary care in Denmark between 2003 and 2006.

Participants Non-obese patients (BMI 27) with preserved beta cell function.

Interventions After a four month run-in period with repaglinide plus metformin combination therapy, patients with a glycated haemoglobin (HbA_1c) concentration of 6.5% or more were randomised to repaglinide 6 mg or metformin 2000 mg. All patients also received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months. Insulin dose was adjusted aiming for a fasting plasma glucose concentration of 4.0-6.0 mmol/l. The target of HbA_1c concentration was less than 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached.

Main outcome measure HbA_1c concentration.

Results Of the 459 patients who were eligible, 102 were randomised, and 97 completed the trial. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA_1c concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA_1c 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P=0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments –2.51 kg, 95% confidence interval –4.07 to –0.95).

Conclusions In non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with insulin in combination with metformin was equivalent to that with insulin plus repaglinide. Weight gain seemed less with insulin plus metformin than with insulin plus repaglinide.

Trial registration NCT00118963 [ClinicalTrials.gov]

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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