Effects of metformin and intensive lifestyle interventions on the incidence of kidney disease in adults in the DPP/DPPOS

Abstract

Aims: We analyzed the incidence of kidney disease in the Diabetes Prevention Program Outcomes Study (DPPOS) by originally randomized treatment group assignment: Intensive Lifestyle (ILS), Metformin (MET) or Placebo (PLB).

Methods: The current analyses used a time-to-event approach in which the primary outcome was kidney disease, ascertained as urine albumin-to-creatinine ratio (ACR) ≥ 3.39 mg/mmol (30 mg/g) or eGFR <45 mL/min/1.73m², with confirmation required at the next visit, or adjudicated end-stage kidney disease (ESKD).

Results: At a median of 21 years following randomization in DPP, diabetes development was reduced in both the ILS (HR 0.73 [95%CI = 0.62, 0.85]) and MET groups (HR 0.85 [0.73, 0.99]) compared to the PLB group. Although risk for developing the primary kidney disease outcome was higher among those with incident diabetes compared to those without (HR 1.81 [1.43, 2.30]), it did not differ by intervention groups (ILS vs. PLB 1.02 (0.81, 1.29); MET vs. PLB 1.08 (0.86, 1.35). There was a non-significant metformin by age interaction (p = 0.057), with metformin being beneficial for kidney disease in the younger but potentially harmful in the older participants.

Conclusions: Development of kidney disease was increased in participants who developed diabetes but did not differ by original treatment group assignment.

Clinical trial registrations: Diabetes Prevention Program (DPP) Clinical trial reg. no. NCT00004992 DPP Outcomes Study (DPPOS) Clinical trial reg. no. NCT0038727.

Trial registration: ClinicalTrials.gov NCT00038727 NCT00004992.

Keywords: Albuminuria; Diabetes mellitus; Glomerular filtration rate; Kidney; Metformin; Nephropathy; Prevention; Type 2.