The effects of metformin versus repaglinide in non-obese patients with type 2 diabetes treated with insulin have been examined in a RCT conducted in secondary care in Denmark between 2003 and 2006.

The study included participants who had had type 2 diabetes for approximately 10 years, BMI ≤ 27 and preserved beta cell function. After a four month run-in period with repaglinide plus metformin combination therapy, those with a HbA1c ≥6.5% (n= 102 but 1 drop out) were randomised to repaglinide 6mg (n= 49) or metformin 2000 mg (n= 52) and 97 completed the trial. All patients received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units/d 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 HbA1c was < 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached. The main outcome measure was HbA1c concentration.

At the end of treatment:

• HbA1c concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin mean HbA1c 8.15% vs. 6.72% and insulin plus repaglinide 8.07% vs. 6.90%; p = 0.177).

• Total daily insulin dose and risk of hypoglycaemia were 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: –2.51kg).

The researchers conclude that in non-obese patients with type 2 diabetes, biphasic insulin aspart 70/30 plus metformin and biphasic insulin aspart 70/30 plus repaglinide are both safe and effective means of glycaemic regulation, but weight gain appeared less with insulin plus metformin than with insulin plus repaglinide.

An accompanying editorial discusses the implications of these findings for general practice, noting that the continuation of metformin after the introduction of insulin in non-obese patients with type 2 diabetes may therefore not only reduce weight but have beneficial cardiovascular effects in the longer term; and if metformin is contraindicated, repaglinide might be a reasonable alternative, at least for one year.