IngentaConnect Effects of early use of pioglitazone in combination with metformi...

Abstract:

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-naïve 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/m², 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 metformin/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 β-cell protective properties of pioglitazone. These results need to be confirmed by further studies with a more robust design and methodology.

Keywords: COMBINATION THERAPY; GLYCAEMIC CONTROL; METFORMIN; PIOGLITAZONE; TYPE 2 DIABETES

Document Type: Case report

DOI: 10.1185/030079907X210606

Affiliations: 1: Diabetes Centre, Victoria Hospital, Kirkcaldy, Fife, UK 2: Hunton Bridge, King's Langley, Hertfordshire, UK 3: Takeda Global Research & Development Centre (Europe) Ltd, London, UK

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