Louis Potier1,2,3, Ronan Roussel4,5,6, Gilberto Velho6, Pierre-Jean Saulnier7,8,9, Anisoara Bumbu4, Odette Matar4, Fabrice Schneider7,8,9,10, Stéphanie Ragot7,8,9, Michel Marre4,5,6,11, Kamel Mohammedi12,13,14, Samy Hadjadj15. 1. Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, DHU FIRE, 46 rue Henri Huchard 75877, Paris Cedex 18, France. louis.potier@gmail.com. 2. UFR de Médecine, Paris Diderot University, Sorbonne Paris Cité, Paris, France. louis.potier@gmail.com. 3. Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France. louis.potier@gmail.com. 4. Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, DHU FIRE, 46 rue Henri Huchard 75877, Paris Cedex 18, France. 5. UFR de Médecine, Paris Diderot University, Sorbonne Paris Cité, Paris, France. 6. Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France. 7. CIC1402, INSERM, Poitiers, France. 8. UFR de Médecine et Pharmacie, Poitiers University, Poitiers, France. 9. Clinical Investigation Centre, CHU de Poitiers, Poitiers, France. 10. Department of Vascular Surgery, Centre Hospitalier Universitaire de Poitiers, Poitiers, France. 11. Fondation Ophtalmologique Adolphe de Rothschild, Paris, France. 12. Department of Diabetology, Endocrinology and Nutrition, Hôpital Haut-Lévêque, Bordeaux, France. 13. Bordeaux University, Bordeaux, France. 14. Inserm U1219 'Bordeaux Population Health', Bordeaux, France. 15. Institut du Thorax, Inserm, CNRS, CHU Nantes, Nantes, France.
Abstract
AIMS/HYPOTHESIS: Recently, safety data signalled an increased risk of amputations in people taking canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If this side effect is due to drug-induced hypovolaemia, diuretics should also increase that risk. The aim of this study was to analyse the association between diuretic use and the risk of lower limb events (LLEs) in people with type 2 diabetes. METHODS: SURDIAGENE (SUivi Rénal, DIAbète de type 2 et GENEtique) is a prospective observational cohort that includes people with type 2 diabetes enrolled from 2002 to 2012 and followed-up until onset of LLE, death or 31 December 2015, whichever came first. Primary outcome was the first occurrence of LLE, a composite of lower limb amputation (LLA) and lower limb revascularisation (LLR). The rates of primary outcome were compared between participants taking and not taking diuretics at baseline in a Cox-adjusted model. RESULTS: At baseline, of the 1459 participants included, 670 were taking diuretics. In participants with and without diuretics, the mean ages were 67.1 and 62.9 years and 55.8% and 59.8% were men, respectively. During a median follow-up of 7.1 years, the incidence of LLE was 1.80 per 100 patient-years in diuretic users vs 1.00 in non-users (p < 0.001). The HR for LLE in users vs non-users was 2.08 (95% CI 1.49, 2.93), p < 0.001. This association remained significant in a multivariable-adjusted model (1.49 [1.01, 2.19]; p = 0.04) and similar after considering death as a competing risk (subhazard ratio 1.89 [1.35, 2.64]; p < 0.001). When separated, LLA but not LLR, was associated with the use of diuretics: 2.01 (1.14, 3.54), p = 0.02 and 1.05 (0.67, 1.64), p = 0.84, respectively, in the multivariable-adjusted model. CONCLUSIONS/ INTERPRETATION: Among people with type 2 diabetes treated with diuretics, there was a significant increase in the risk of LLE, predominantly in the risk of LLA.
AIMS/HYPOTHESIS: Recently, safety data signalled an increased risk of amputations in people taking canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If this side effect is due to drug-induced hypovolaemia, diuretics should also increase that risk. The aim of this study was to analyse the association between diuretic use and the risk of lower limb events (LLEs) in people with type 2 diabetes. METHODS: SURDIAGENE (SUivi Rénal, DIAbète de type 2 et GENEtique) is a prospective observational cohort that includes people with type 2 diabetes enrolled from 2002 to 2012 and followed-up until onset of LLE, death or 31 December 2015, whichever came first. Primary outcome was the first occurrence of LLE, a composite of lower limb amputation (LLA) and lower limb revascularisation (LLR). The rates of primary outcome were compared between participants taking and not taking diuretics at baseline in a Cox-adjusted model. RESULTS: At baseline, of the 1459 participants included, 670 were taking diuretics. In participants with and without diuretics, the mean ages were 67.1 and 62.9 years and 55.8% and 59.8% were men, respectively. During a median follow-up of 7.1 years, the incidence of LLE was 1.80 per 100 patient-years in diuretic users vs 1.00 in non-users (p < 0.001). The HR for LLE in users vs non-users was 2.08 (95% CI 1.49, 2.93), p < 0.001. This association remained significant in a multivariable-adjusted model (1.49 [1.01, 2.19]; p = 0.04) and similar after considering death as a competing risk (subhazard ratio 1.89 [1.35, 2.64]; p < 0.001). When separated, LLA but not LLR, was associated with the use of diuretics: 2.01 (1.14, 3.54), p = 0.02 and 1.05 (0.67, 1.64), p = 0.84, respectively, in the multivariable-adjusted model. CONCLUSIONS/ INTERPRETATION: Among people with type 2 diabetes treated with diuretics, there was a significant increase in the risk of LLE, predominantly in the risk of LLA.
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