ROLE OF METFORMIN IN ADPKD: EXPERIENCE FROM A TERTIARY CARE CENTRE IN EASTERN INDIA

Introduction:

ADPKD, the most common of the inherited renal cystic diseases, accounts for 2.6% cases of CKD in India. Metformin acting via the AMPK pathway has shown to impact cystogenesis and in preclinical animal models retards the progression of ADPKD. Few studies have highlighted the safety profile of Metformin in ADPKD patients but large studies on therapeutic efficacy are lacking. We evaluated the effect of Metformin therapy on the progression of ADPKD by comparing the changes of height adjusted total kidney volume (htTKV) and of estimated glomerular filtration rate (eGFR) in between groups on Metformin and Placebo over a period of 12 months across different Mayo imaging classes

Methods:

ADPKD patients were randomized into Metformin and Placebo arm in 2:1 ratio and followed up by annual monitoring of htTKV by MRI and eGFR by Creatinine measurement. All received standard of care therapy with anti-hypertensives and dietary interventions, with additional intervention of daily Metformin in the intervention arm. Each group was compared in terms of eGFR loss and percentage increase in htTKV with further sub classification into Mayo Class based on htTKV. Data was analysed as per Intention to treat analysis with group mean or median as missing data imputation

Results:

Total 254 patients with polycystic Kidneys were screened, of which 224 patients fulfilled the inclusion criteria. Further 33 patients were excluded due to various reasons as atypical Class 2 PKD on MRI, Mutations other than PKD1,2 on evaluation. Final analyses included 121 patients in Metformin arm and 71 in placebo arm (51% male and 49% female). Pain in abdomen was the most common presenting symptom at the time of diagnosis. Hypertension (63%) was the most prevalent comorbidity.

The patients were grouped according to the respective Mayo Imaging class due to the variation in the baseline parameters and difference in the rate of progression of disease. Classes A and B were analyzed together, and Classes C, D and E were analyzed together.

In Mayo Class 1A and 1B, comparison of the median loss and percentage change of eGFR showed no significant difference in both arms. No difference in median increase and percentage change of htTKV from the baseline values was observed.

In Mayo class 1C, 1D and 1E, no difference could be observed in terms of median loss and percentage change of eGFR in both arms. However, the median increase in htTKV in both the arms showed a significantly less increase in the group on Metformin therapy. Similarly, the percentage change was significantly less in the metformin arm as compared to the placebo arm. It shows a possible benefit in terms of reduction in the progression of ADPKD with Metformin therapy. Higher incidence of dyspepsia was noted in the Metformin arm, though the difference was statistically insignificant.

Conclusions:

Metformin therapy showed significant benefit in terms of htTKV changes in Mayo class 1C, 1D and 1E. However, it did not translate into significant benefit in regards to prevention of loss of eGFR in any of the Mayo classes. As the period of study was short, there is a need for larger study with longer follow up to establish the accurate role of Metformin in the treatment of ADPKD.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.