Aims: Poor glycemic control may contribute to the very high mortality rate in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) . Whether analogue compared to human insulin therapy associates with different outcomes is unknown.

Methods: Incident HD patients with T2D on insulin treatment enrolled at one of the 288 Fresenius Medical Care facilities across 7 European countries between 2007-20were identified using an established administrative data algorithm. All patients were censored after 3 years of observation. Following multiple imputation, inverse probably weighting (IPW) and instrumental variable (IV; using country) analyses were used to generate Cox-proportional hazards to estimate analogue compared to human insulin hazard ratios for all-cause mortality (ACM) , MACE, hospitalization, and confirmed hypoglycemia (<3.0 mmol/L during a dialysis session) .

Results: About 713 analogue users were compared to 733 subjects treated with human insulin. Significant variation in prescription by country was observed. IPW hazard ratios [95% confidence intervals] for patients on analogue compared to human insulin were 0.8[0.659-0.991] for ACM (p=0.042) , 0.817 [0.679-0.983] for MACE (p=0.033) , 0.757 [0.665-0.861] for hospitalization (p<0.001) , and 1.6[1.1419-2.268] for hypoglycemia (p=0.008) . Consistent strength and direction of the associations were observed in the IV analysis and across sensitivity analyses.

Conclusions: In this large, multinational cohort of patients with T2D on HD, compared to human insulins, analogue insulins were associated with better clinical outcomes, although hypoglycemia rates were increased. Whether analogue insulins represent the preferred therapy in this group requires confirmatory evidence from a clinical trial.


T. Ebert: Consultant; Sanofi, Santis. Research Support; AstraZeneca, Novo Nordisk. N. Sattar: None. M. Greig: None. C. Lamina: None. K. Eckardt: Consultant; Akebia Therapeutics, Inc. Research Support; Bayer AG, Evotec International GmbH, Fresenius Medical Care. Speaker's Bureau; AstraZeneca, Bayer AG, Otsuka Pharmaceutical Co., Ltd. J. Floege: Other Relationship; Novo Nordisk A/S. F. Kronenberg: Advisory Panel; Amgen Inc., Novartis AG. P. Stenvinkel: Advisory Panel; AstraZeneca, Baxter, Fresenius Medical Care, Reata Pharmaceuticals, Inc., Vifor Pharma Management Ltd. Speaker's Bureau; Astellas Pharma Inc., Bayer AG, Novo Nordisk. D.C. Wheeler: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Global Services, LLC, Merck Sharp & Dohme Corp., Mundipharma, Tricida, Inc., Vifor Pharma Management Ltd. Consultant; AstraZeneca. Speaker's Bureau; Amgen Inc., Astellas Pharma Inc. J. Fotheringham: Advisory Panel; Novartis Pharmaceuticals Corporation. Speaker's Bureau; Fresenius Medical Care, Novartis Pharmaceuticals Corporation, Vifor Pharma Management Ltd.


Amgen (Europe) GmbH- Rotkreuz, Switzerland- Swedish Research Council (grant 2009-1068) - Swedish Heart and Lung Foundation (20160384) - Njurfonden- Westmans Foundation- Novo Nordisk (Postdoctoral fellowship program run inpartnership with Karolinska Institutet, Stockholm,Sweden) - Karolinska Institutet Research Foundation - EFSD (EFSD Mentorship Programme supported by AstraZeneca) - German Research Foundation (SFB TRR 219, projects C1 and M1) - National Institute for Health Research (UK) (Clinician Scientist Award)

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