Baseline albuminuria in patients with diabetic kidney disease (DKD) is strongly associated with progressive deterioration in kidney function (1). The remission of microalbuminuria in patients with type 2 diabetes and obesity attenuates the decline in estimated glomerular filtration rate (2). In the Microvascular Outcomes after Metabolic Surgery (MOMS) randomized controlled trial (RCT) (3), we demonstrated that the combination of best medical care and Roux-en-Y gastric bypass (RYGB) surgery is more effective in inducing remission of microalbuminuria than best medical care alone.

During the MOMS RCT, type 2 diabetes care guidelines were updated to reflect the potent renoprotective effects of sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in people with DKD (4). Thus, the rate of use of the combination of these two agents (Combo) in the study was increased. In this post hoc analysis of the MOMS RCT, our objective was to determine whether the combination of two potent renoprotective medications can match the reductions of albuminuria observed after RYGB.

The MOMS RCT protocol has previously been described in detail (3). In brief, 100 patients with CKDG1–3a, A2–3, urine albumin–to–creatinine-ratio (uACR) >30 mg/g, type 2 diabetes, and a BMI of 30–35 kg/m2 were randomized 1:1 to either best medical care or RYGB. Of the 49 patients, 27 (55%) randomized to best medical treatment received the Combo (empagliflozin 25 mg once daily and liraglutide 1.8 mg once daily) within the first 2 years of the study and formed the subgroup of interest for this post hoc analysis. A total of 44 patients who underwent RYGB and completed 2 years of follow-up were included in this analysis. uACR, estimated glomerular filtration rate, glycated hemoglobin (HbA1c), fasting plasma glucose, blood pressure, lipid profiles, and body weight were assessed at baseline and 2 years.

Both interventions resulted in significant reductions in uACR, but RYGB was significantly superior (mean difference 14.99 [95% CI 1.10; 28.87], P = 0.035) (Table 1). The percentage of patients who achieved remission of albuminuria/DKD was 59.3% in the Combo and 81.8% in the RYGB group (P = 0.043).

RYGB was superior to the Combo for reductions in HbA1c (mean difference 0.49 [95% CI 0.05; 0.93], P = 0.029) and LDL cholesterol (20.55 [6.30; 34.81], P = 0.005) but not systolic blood pressure (−0.75 [−8.51; 7.02], P = 0.82). The American Diabetes Association (ADA) triple end point was achieved in 25.9% in the Combo group and 44.2% in the RYGB group (P = 0.11).

In this post hoc analysis of the MOMS trial, the effect of inclusion of two potent renoprotective agents in best medical care for people with DKD did not quite match the renoprotective effects of RYGB. The surgical intervention remained superior in reducing albuminuria, remission of DKD, and improvements in cardiometabolic risk factors, including HbA1c and LDL cholesterol. Despite the statistical superiority of surgery, the differences in primary and secondary outcomes of the trial were of modest biological significance.

While modern pharmacotherapy for type 2 diabetes cannot fully recapitulate the pleiotropic impact of RYGB on DKD at the current time, with the rapid evolution of medicines, this might be possible in the future.

Clinical trial reg. no. NCT01821508, clinicaltrials.gov

Funding. This study was partly supported by research grants from Oswaldo Cruz German Hospital, Science Foundation Ireland (grant 12/YI/B2480), and the Swedish Medical Research Council (2015-02733). The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, Biotechnology and Biological Sciences Research Council, and National Institute for Health Research (NIHR); an Integrative Mammalian Biology Capacity Building Award; and an FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Biomedical Research Centre funding scheme.

The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care.

Duality of Interest. This study was also supported by funding from Johnson & Johnson Brasil. R.V.C. reports receiving grants from Johnson & Johnson Brasil during the conduct of the study. T.B.Z.P. reports receiving grants from Johnson & Johnson Brasil during the conduct of the study. A.D.M. reports receiving honoraria for lectures and serving on the scientific advisory board from Novo Nordisk, GI Dynamics, and Boehringer Ingelheim outside the submitted work. C.W.l.R. reports receiving honoraria for lectures and serving on the scientific advisory board from Novo Nordisk, GI Dynamics, Sanofi, Johnson & Johnson Brasil, Keyron, Herbalife Nutrition, and Boehringer Ingelheim outside the submitted work. No other potential conflicts of interest relevant to this article were reported.

Author Contributions. R.V.C., T.B.Z.P., and C.W.l.R. contributed to the study concept and design. R.V.C., T.B.Z.P., C.M.A., and C.W.l.R. contributed to acquisition, analysis, or interpretation of data. R.V.C., A.D.M., C.M.A., B.J., and C.W.l.R. contributed to drafting of the manuscript. R.V.C., A.D.M., C.M.A., T.B.Z.P., and C.W.l.R. contributed to critical revision of the manuscript for important intellectual content. T.M.d.S. contributed to statistical analysis. R.V.C. obtained funding. R.V.C., T.B.Z.P., C.M.A., and B.J. contributed to administrative, technical, or material support. R.V.C. and C.W.l.R. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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