The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system - PubMed (original) (raw)

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The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system

Guntram Schernthaner et al. Diab Vasc Dis Res. 2014 Sep.

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Abstract

Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway.

Keywords: Diabetic nephropathy; glomerular filtration rate; incretin; renal impairment; type 2 diabetes.

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Conflict of interest statement

Declaration of conflicting interests: Guntram Schernthaner has received lecture fees from Amgen, AstraZeneca/Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline (GSK), Merck Sharp & Dohme (MSD), Novartis, Novo Nordisk, Sanofi-Aventis, Servier and Takeda. Carl Erik Mogensen has declared no conflicts of interest. Gerit-Holger Schernthaner has received scientific grants and/or educational grants and/or travel grants and/or slide honoraria, and/or lecture honoraria, and/or advisory board honoraria, and/or contract research and/or partner research from/with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Medtronic, Menarini, Merck, MSD, Novo Nordisk, Novartis, Pfizer, Sanofi, Sanofi-Aventis, Servier and Takeda in the past 10 years.

Figures

Figure 1.

Prevalence of CKD among US adults by disease stage – National Health and Nutrition Examination Survey (NHANES), United States, 1999–2004. Data source: Saydah et al. CKD: chronic kidney disease.

Figure 2.

DPP-4 effects beyond glucose lowering. Source: Republished with permission of The Endocrine Society, from Ussher and Drucker. ©2014. BNP: B-type (brain) natriuretic peptide; DPP-4: dipeptidyl peptidase-4; GIP: glucose-dependent insulinotropic polypeptide; GLP-1: glucagon-like peptide-1; NPY: neuropeptide; PYY: peptide YY; SDF-1α: stromal cell-derived factor-1α; SP: substance P.

Figure 3.

Antidiabetes therapy in patients with CKD. Source: Modified from Schernthaner et al., by permission of Oxford University Press. CKD: chronic kidney disease; ESRD: end-stage renal disease; RI: renal impairment. aInsulin dosing should be monitored and adjusted depending upon the patient’s response. bSitagliptin dose adjusted to 50 mg once daily for patients with moderate RI, or to 25 mg once daily for patients with severe RI or ESRD. cSaxagliptin dose adjusted to 2.5 mg once daily for patients with moderate-to-severe RI, or ESRD. dVildagliptin dose adjusted to 50 mg once daily for patients with moderate-to-severe RI, or ESRD. eGlimepiride dose should be started at 1 mg daily for all patients with RI. fMetformin dose in patients with moderate RI varies according to national guidelines.

Figure 4.

Changes in eGFR over time in T2DM patients with moderate RI treated with (a) canagliflozin and (b) dapagliflozin. Moderate RI = baseline eGFR ≥30 and <50 mL/min/1.73 m2; Moderate RI = baseline eGFR ≥30 and <60 mL/min/1.73 m2. Placebo (circles, solid line), dapagliflozin 5 mg (squares, dashed line) and dapagliflozin 10 mg (triangles, dotted line). Source: Reprinted by permission from Yale et al. ©2013 Blackwell Publishing Ltd; Reprinted by permission from Macmillan Publishers Ltd: Kidney International (Kohan et al. Copyright©2014). CANA: canagliflozin; eGFR: estimated glomerular filtration rate; LS: least squares; PBO: placebo; RI: renal impairment; SE: standard error; T2DM: type 2 diabetes mellitus.

Figure 5.

Proportion of participants in canagliflozin cardiovascular safety study in patients with T2DM experiencing a ≥1-step progression in albuminuria stage. Source: Coelln-Hough et al. T2DM: type 2 diabetes mellitus.

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The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system - PubMed (original) (raw)