![]() received speaker honorarium from Novartis, Novo Nordisk, Eli Lilly and Company, and Sanofi and attends advisory board meetings for Sanofi and AstraZeneca. is on the advisory board for Novo Nordisk, Eli Lilly and Company, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, Johnson & Johnson, Novartis, and AstraZeneca received grants paid to an institution as study physician by AstraZeneca and Bristol-Myers Squibb received research grant support through Hadassah Hebrew University Hospital from Novo Nordisk and is on the speaker's bureau for AstraZeneca, Bristol-Myers Squibb, Novo Nordisk, Eli Lilly and Company, Sanofi, Novartis, Merck Sharp & Dohme, Kyowa Hakko Kirin Co., Ltd., and Boehringer Ingelheim. Prospective Diabetes Study 74 (UKPDS) trial ( 28) therefore, the effects of treatment on albuminuria and eGFR might be dissimilar.ĭuality of Interest. Additionally, the multivariable analysis of variables associated with eGFR and ACR ( Supplementary Table 2) showed incomplete overlap between variables affecting albuminuria and eGFR, as was previously shown in the U.K. ![]() A somewhat similar result and conclusion was reported in the post hoc analysis of the ALTITUDE trial, in which the addition of aliskiren, a renin inhibitor, to treatment with ACEI or ARB was associated with decrease in ACR without renal or CV-protective effect ( 27). Possible explanations for this inconsistency might be the short duration of follow-up in SAVOR-TIMI 53 and/or the extent of the change in ACR. In the current study, treatment with saxagliptin reduced ACR without affecting the eGFR. The clinical significance of the reduction of albuminuria by saxagliptin, without any effect on other renal outcomes, on the development and progression of renal dysfunction and CV morbidity is unknown.Ī recent meta-analysis included 21 trials and 78,342 patients and demonstrated that reducing albuminuria by various pharmacological interventions was strongly associated with decreased progression to ESRD ( 25). Lastly, decreased ACR in saxagliptin-treated patients seemed to be independent of saxagliptin's effect on glycemia. Because the association between ACR levels and increased CV risk can be demonstrated even within the normoalbuminuric range, ACR reduction by saxagliptin in this range might have future possible positive effects not demonstrated in the present trial ( 22). The improvement in ACR was observed when ACR was analyzed as either a continuous or categorical variable at all baseline ACR and eGFR categories. The clinical significance of this observation is not known. The main finding of this prespecified secondary analysis is that treatment with saxagliptin was associated with a reduction in ACR compared with placebo. Treatment with saxagliptin was found to be safe with regard to renal outcomes however, the study did not demonstrate improvement in hard renal outcomes such as doubling of creatinine or initiation of renal replacement therapy. The SAVOR-TIMI 53 study included a large population of patients with T2D at high CV risk with diverse baseline renal characteristics, including a substantial number of patients with renal dysfunction and/or albuminuria. 1).ĭemographic characteristics and baseline measurementsįasting serum glucose (mg/dL), median (IQR) Of those patients, 44.4 and 19.5% with moderate and severe renal impairment, respectively, had normoalbuminuria ( Supplementary Fig. ![]() Although there was a tendency for higher ACR values with lower eGFR categories, there were still a substantial number of patients with normoalbuminuria among those with reduced eGFR ( Supplementary Fig. ![]() The number of patients in each eGFR and ACR group at baseline was balanced between treatment arms. The population distribution by eGFR and ACR categories at baseline, 1 year, and EOT is shown ( Supplementary Table 1). The saxagliptin and placebo arms were balanced with regard to baseline eGFR and ACR categories. A total of 9,696 (58.8%) patients had normoalbuminuria, 4,426 (26.8%) patients had microalbuminuria, 1,638 (9.9%) patients had macroalbuminuria, and 732 (4.4%) patients had no ACR measurement at baseline. Of the 16,492 patients, 13,916 (84.4%) had normal or mildly impaired renal function, 2,240 (13.6%) had moderate renal impairment, and 336 (2.0%) had severe renal impairment. Treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial (EOT) ( P = 0.021, P 50 mL/min/body surface area per 1.73 m 2 (BSA), −105 mg/g ( P = 0.011) for 50 ≥ eGFR ≥ 30 mL/min/BSA, and −245.2 mg/g ( P = 0.086) for eGFR 6.0 mg/dL, were similar as well. At baseline, 9,696 (58.8%) subjects had normoalbuminuria (albumin/creatinine ratio 300 mg/g). ![]()
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