Effects of early use of pioglitazone in combination with metformin in patients with newly diagnosed type 2 diabetes

Background: Type 2 diabetes is characterised by a progressive decline in HbA(1c) control over time. Early combination therapy, rather than sequential introduction of individual oral glucose-lowering agents, has been proposed to prevent this gradual rise in HbA(1c). This observational study assessed the effect of early dual combination oral glucose-lowering therapies within 6 months of diagnosis in newly diagnosed, drug-naive patients with type 2 diabetes. Patients and methods: This was an observational, open-label,non-randomised study in newly diagnosed patients with type 2 diabetes, aged 35-70 years, with HbA(1c) levels >8.0% at diagnosis or > 7.0% at the 3-6-month follow-up. Patients were allocated to dietary management alone if the HbA(1c) level was 7.0-8.0% at diagnosis. Metformin combined with gliclazide, repaglinide, or pioglitazone was given at diagnosis if the HbA(1c) was > 8.0%. Similar treatments were introduced at 3-6 months if the HbA(1c) was > 7.0%. Over a 3-year period, HbA(1c) was measured at 3-monthly intervals. All patients underwent regular dietetic review. Target HbA(1c) was <= 7.0%. Results. 416 patients were considered eligible for inclusion, with a mean ( +/-SD) age of 54.1 +/- 9.2 years, BMI of 33.5 +/- 6.1 kg/m(2), and baseline HbA(1c) of 8.6 +/- 1.7%. A mixed model analysis of variance on the 178 patients who started with combination therapy, either immediately or after a 3-6 month period on diet, showed that metformin plus gliclazide, repaglinide, or pioglitazone was associated with a gradual increase in HbA(1c) values. Amongst those patients treated with the mefformin/pioglitazone combination there was an estimated 0.1 % increase in HbA(1c)/year. This was much less pronounced than the rises seen in HbA(1c)/year of 0.5% with the metformin/gliclazide and metformin/repaglinide combinations. Conclusions: This preliminary analysis of an obervational, non-randomised, open-label ongoing study has shown that early use of combination therapy at time of diagnosis or within the first 3-6 months following diagnosis with metformin plus pioglitazone in newly diagnosed type 2 diabetes results in a slower deterioration in glycaemic control than that with metformin combined with either gliclazide or repaglinide, This may be due to the beta-cell protective properties of pioglitazone. These results need to be confirmed by further studies with a more robust design and methodology.