Renal function in type 2 diabetes with rosiglitazone, metformin, and glyburide monotherapy

Abstract

Background and objectives: In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups.

Design, setting, participants, & measurements: A total of 4351 recently diagnosed, drug-naïve patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP.

Results: The ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR ≥30 mg/g), hypertension, or impaired eGFR (<60 ml/min per 1.73 m(2)).

Conclusions: Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators.

Trial registration: ClinicalTrials.gov NCT00279045.

Figure 1.

Mean or geometric mean levels of measures from a baseline-adjusted longitudinal normal errors regression model with 95% confidence limits. (A) Albumin-to-creatinine ratio (ACR, mg/g); (B) MDRD-estimated GFR (GFR; ml/min per 1.73 m²); (C) systolic BP (mmHg); (D) diastolic BP (mmHg).

Figure 2.

Cumulative incidence of events among groups with 95% confidence limits. (A) Progression from normal albumin-to-creatinine ratio (ACR <30 mg/g) to albuminuria (ACR ≥30 mg/g); (B) progression from normal or high estimated GFR (eGFR ≥60 ml/min per 1.73 m²) to impaired eGFR (<60 ml/min per 1.73 m²); (C) change from normal eGFR (60 ≤ eGFR ≤ 130 ml/min per 1.73 m²) to high eGFR (>130 ml/min per 1.73 m²); (D) onset of hypertension or initiation of antihypertensive medications.