The treatment of
NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50
NIDDM patients with secondary failure to
glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime
NPH insulin or a t.i.d. oral
metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined
therapies clearly improved glycaemic control.
HbA1 c were similarly reduced by the addition of either bedtime
NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or
metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma
glucose (FPG) and post-prandial plasma
glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time
NPH insulin was more effective on FPG reduction than
metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast,
metformin addition was more effective on PPPG reduction than bedtime
NPH insulin addition (-30+/-2% vs 20+/-3%, p<0.01). Serum
cholesterol was marginally but significantly decreased after
metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after
NPH insulin.
Body weight increase was significantly greater after
insulin addition than after
metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of
metformin rather than
NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG,
HbA1 c, post-
glucagon C-peptide levels,
insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in
NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime
NPH insulin or t.i.d.
metformin is similarly effective in improving glycaemic control.
Metformin is better accepted by patients and provides a modest advantage in terms of
body weight and
cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments.