Skip to main content
Erschienen in: Acta Diabetologica 5/2021

23.01.2021 | Original Article

The effects of saxagliptin on cardiac structure and function using cardiac MRI (SCARF)

verfasst von: Paul Sandhu, Jann P. Ong, Vinay Garg, Mustafa Altaha, Olubenga Bello, Sewa R. Singal, Subodh Verma, Andrew T. Yan, Kim A. Connelly

Erschienen in: Acta Diabetologica | Ausgabe 5/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose

A recent large cardiovascular outcome trial in patients with type 2 diabetes (T2DM) demonstrated excess heart failure hospitalization with saxagliptin. We sought to evaluate the impact of saxagliptin on cardiac structure and function using cardiac magnetic resonance imaging (CMR) in patients with T2DM without pre-existing heart failure.

Methods

In this prospective study, patients with T2DM without heart failure were prescribed saxagliptin as part of routine guideline-directed management. Clinical assessment, CMR imaging and biomarkers were assessed in a blinded fashion and compared following 6 months of continued treatment. The primary outcome was the change in left ventricular (LV) ejection fraction (LVEF) after 6 months of therapy. Key secondary outcomes included changes in LV and right ventricular (RV) end-diastolic volume, ventricular mass, LV global strain and cardiac biomarkers [N terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP)] over 6 months.

Results

The cohort (n = 16) had a mean age of 59.9 years with 69% being male. The mean hemoglobin A1c (HbA1c) was 8.3%. Mean baseline LVEF was 57% ± 3.4, with no significant change over 6 months (− 0.2%, 95% CI − 2.5, 2.1, p = 0.86). Detailed CMR analyses that included LV/RV volumes, LV mass, and feature tracking-derived strain showed no significant change (all p > 0.50). NT-proBNP and hsCRP levels did not significantly change (p > 0.20).

Conclusions

In this cohort of stable ambulatory patients with T2DM without heart failure, saxagliptin treatment was not associated with adverse ventricular remodeling over 6 months as assessed using CMR and biomarkers.
Literatur
1.
Zurück zum Zitat MacDonald MR, Petrie MC, Hawkins NM et al (2008) Diabetes, left ventricular systolic dysfunction, and chronic heart failure. Eur Heart J 29(10):1224–1240CrossRef MacDonald MR, Petrie MC, Hawkins NM et al (2008) Diabetes, left ventricular systolic dysfunction, and chronic heart failure. Eur Heart J 29(10):1224–1240CrossRef
2.
Zurück zum Zitat MacDonald MR, Petrie MC, Varyani F et al (2008) Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure—an analysis of the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 29(11):1377–1385CrossRef MacDonald MR, Petrie MC, Varyani F et al (2008) Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure—an analysis of the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 29(11):1377–1385CrossRef
3.
Zurück zum Zitat Dauriz M, Targher G, Laroche C et al (2017) Association between diabetes and 1-year adverse clinical outcomes in a multinational cohort of ambulatory patients with chronic heart failure: results from the ESC-HFA Heart Failure Long-Term Registry. Diabetes Care 40(5):671–678CrossRef Dauriz M, Targher G, Laroche C et al (2017) Association between diabetes and 1-year adverse clinical outcomes in a multinational cohort of ambulatory patients with chronic heart failure: results from the ESC-HFA Heart Failure Long-Term Registry. Diabetes Care 40(5):671–678CrossRef
4.
Zurück zum Zitat Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369(14):1317–1326CrossRef Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369(14):1317–1326CrossRef
5.
Zurück zum Zitat Green JB, Bethel MA, Armstrong PW et al (2015) Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 373(3):232–242CrossRef Green JB, Bethel MA, Armstrong PW et al (2015) Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 373(3):232–242CrossRef
6.
Zurück zum Zitat McGuire DK, Alexander JH, Johansen OE et al (2019) Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation 139(3):351–361CrossRef McGuire DK, Alexander JH, Johansen OE et al (2019) Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation 139(3):351–361CrossRef
7.
Zurück zum Zitat McMurray JJV, Ponikowski P, Bolli GB et al (2018) Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. JACC Heart Fail 6(1):8–17CrossRef McMurray JJV, Ponikowski P, Bolli GB et al (2018) Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. JACC Heart Fail 6(1):8–17CrossRef
8.
Zurück zum Zitat Verma S, Goldenberg RM, Bhatt DL et al (2017) Dipeptidyl peptidase-4 inhibitors and the risk of heart failure: a systematic review and meta-analysis. CMAJ Open 5(1):E152–E177CrossRef Verma S, Goldenberg RM, Bhatt DL et al (2017) Dipeptidyl peptidase-4 inhibitors and the risk of heart failure: a systematic review and meta-analysis. CMAJ Open 5(1):E152–E177CrossRef
9.
Zurück zum Zitat Mannucci E, Mosenzon O, Avogaro A (2016) Analyses of results from cardiovascular safety trials with DPP-4 inhibitors: cardiovascular outcomes, predefined safety outcomes, and pooled analysis and meta-analysis. Diabetes Care 39(S2):S196–S204CrossRef Mannucci E, Mosenzon O, Avogaro A (2016) Analyses of results from cardiovascular safety trials with DPP-4 inhibitors: cardiovascular outcomes, predefined safety outcomes, and pooled analysis and meta-analysis. Diabetes Care 39(S2):S196–S204CrossRef
10.
Zurück zum Zitat Fu AZ, Johnston SS, Ghannam A et al (2016) Association between hospitalization for heart failure and dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: an observational study. Diabetes Care 39(5):726–734CrossRef Fu AZ, Johnston SS, Ghannam A et al (2016) Association between hospitalization for heart failure and dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: an observational study. Diabetes Care 39(5):726–734CrossRef
11.
Zurück zum Zitat Scirica BM, Braunwald E, Raz I et al (2014) Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 130(18):1579–1588CrossRef Scirica BM, Braunwald E, Raz I et al (2014) Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 130(18):1579–1588CrossRef
12.
Zurück zum Zitat Frederich R, Alexander JH, Fiedorek FT et al (2010) A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med 122(3):16–27CrossRef Frederich R, Alexander JH, Fiedorek FT et al (2010) A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med 122(3):16–27CrossRef
13.
Zurück zum Zitat Iqbal N, Parker A, Frederich R et al (2014) Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials. Cardiovasc Diabetol 13:33CrossRef Iqbal N, Parker A, Frederich R et al (2014) Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials. Cardiovasc Diabetol 13:33CrossRef
14.
Zurück zum Zitat Toh S, Hampp C, Reichman ME et al (2016) Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Ann Int Med 164(11):705–714CrossRef Toh S, Hampp C, Reichman ME et al (2016) Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Ann Int Med 164(11):705–714CrossRef
15.
Zurück zum Zitat Constantine G, Shan K, Flamm SD, Sivananthan MU (2004) Role of MRI in clinical cardiology. Lancet 363(9427):2162–2171CrossRef Constantine G, Shan K, Flamm SD, Sivananthan MU (2004) Role of MRI in clinical cardiology. Lancet 363(9427):2162–2171CrossRef
16.
Zurück zum Zitat Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ (2000) Reduction in sample size for studies of remodeling in heart failure by the use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2(4):271–278CrossRef Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ (2000) Reduction in sample size for studies of remodeling in heart failure by the use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2(4):271–278CrossRef
17.
Zurück zum Zitat Chung AK, Das SR, Leonard D et al (2006) Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume: the Dallas Heart Study. Circulation 113(12):1597–1604CrossRef Chung AK, Das SR, Leonard D et al (2006) Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume: the Dallas Heart Study. Circulation 113(12):1597–1604CrossRef
18.
Zurück zum Zitat Grothues F, Smith GC, Moon JCC et al (2002) Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol 90(1):29–34CrossRef Grothues F, Smith GC, Moon JCC et al (2002) Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol 90(1):29–34CrossRef
19.
Zurück zum Zitat Götte MJW, Germans T, Rüssel IK et al (2006) Myocardial strain and torsion quantified by cardiovascular magnetic resonance tissue tagging: studies in normal and impaired left ventricular function. J Am Coll Cardiol 48(10):2002–2011CrossRef Götte MJW, Germans T, Rüssel IK et al (2006) Myocardial strain and torsion quantified by cardiovascular magnetic resonance tissue tagging: studies in normal and impaired left ventricular function. J Am Coll Cardiol 48(10):2002–2011CrossRef
20.
Zurück zum Zitat Ong G, Brezden-Masley C, Dhir V et al (2018) Myocardial strain imaging by cardiac magnetic resonance for detection of subclinical myocardial dysfunction in breast cancer patients receiving trastuzumab and chemotherapy. Int J Cardiol 261:228–233CrossRef Ong G, Brezden-Masley C, Dhir V et al (2018) Myocardial strain imaging by cardiac magnetic resonance for detection of subclinical myocardial dysfunction in breast cancer patients receiving trastuzumab and chemotherapy. Int J Cardiol 261:228–233CrossRef
21.
Zurück zum Zitat Verma S, Mazer D, Yan AT, Mason T, Garg V, Teoh H et al (2019) Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease. Circulation 140(21):1693–1702CrossRef Verma S, Mazer D, Yan AT, Mason T, Garg V, Teoh H et al (2019) Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease. Circulation 140(21):1693–1702CrossRef
22.
Zurück zum Zitat Opie LH, Commerford PJ, Gersh BJ, Pfeffer MA (2006) Controversies in ventricular remodelling. Lancet 367(9507):356–367CrossRef Opie LH, Commerford PJ, Gersh BJ, Pfeffer MA (2006) Controversies in ventricular remodelling. Lancet 367(9507):356–367CrossRef
23.
Zurück zum Zitat Borlaug BA, Redfield MM (2011) Diastolic and systolic heart failure are distinct phenotypes within the heart failure spectrum. Circulation 123(18):2006–2013CrossRef Borlaug BA, Redfield MM (2011) Diastolic and systolic heart failure are distinct phenotypes within the heart failure spectrum. Circulation 123(18):2006–2013CrossRef
24.
Zurück zum Zitat Juillière Y, Barbier G, Feldmann L et al (1997) Additional predictive value of both left and right ventricular ejection fractions on long-term survival in idiopathic dilated cardiomyopathy. Eur Heart J 18(2):276–280CrossRef Juillière Y, Barbier G, Feldmann L et al (1997) Additional predictive value of both left and right ventricular ejection fractions on long-term survival in idiopathic dilated cardiomyopathy. Eur Heart J 18(2):276–280CrossRef
25.
Zurück zum Zitat White WB, Cannon CP, Heller SR et al (2013) Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 369(14):1327–1335CrossRef White WB, Cannon CP, Heller SR et al (2013) Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 369(14):1327–1335CrossRef
26.
Zurück zum Zitat McGuire DK, Van De Werf F et al (2016) Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: secondary analysis of a randomized clinical trial. JAMA Cardiol 1(2):126–135CrossRef McGuire DK, Van De Werf F et al (2016) Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: secondary analysis of a randomized clinical trial. JAMA Cardiol 1(2):126–135CrossRef
27.
Zurück zum Zitat Fadini GP, Bonora BM, Albiero M et al (2017) DPP-4 inhibition has no acute effect on BNP and its N-terminal pro-hormone measured by commercial immune-assays. A randomized cross-over trial in patients with type 2 diabetes. Cardiovasc Diabetol 16(1):22CrossRef Fadini GP, Bonora BM, Albiero M et al (2017) DPP-4 inhibition has no acute effect on BNP and its N-terminal pro-hormone measured by commercial immune-assays. A randomized cross-over trial in patients with type 2 diabetes. Cardiovasc Diabetol 16(1):22CrossRef
28.
Zurück zum Zitat Pellicori P, Zhang J, Cuthbert J, Urbinati A et al (2020) High-sensitivity C-reactive protein in chronic heart failure: patient characteristics, phenotypes, and mode of death. Cardiovasc Res 116(1):91–100CrossRef Pellicori P, Zhang J, Cuthbert J, Urbinati A et al (2020) High-sensitivity C-reactive protein in chronic heart failure: patient characteristics, phenotypes, and mode of death. Cardiovasc Res 116(1):91–100CrossRef
29.
Zurück zum Zitat Jurcut R, Wildiers H, Ganame J et al (2008) Strain rate imaging detects early cardiac effects of pegylated liposomal Doxorubicin as adjuvant therapy in elderly patients with breast cancer. J Am Soc Echocardiogr 21(12):1283–1289CrossRef Jurcut R, Wildiers H, Ganame J et al (2008) Strain rate imaging detects early cardiac effects of pegylated liposomal Doxorubicin as adjuvant therapy in elderly patients with breast cancer. J Am Soc Echocardiogr 21(12):1283–1289CrossRef
30.
Zurück zum Zitat Scheen AJ (2020) Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: a systematic review of randomized controlled trials. Diabetes Metab 46(3):186–196CrossRef Scheen AJ (2020) Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: a systematic review of randomized controlled trials. Diabetes Metab 46(3):186–196CrossRef
Metadaten
Titel
The effects of saxagliptin on cardiac structure and function using cardiac MRI (SCARF)
verfasst von
Paul Sandhu
Jann P. Ong
Vinay Garg
Mustafa Altaha
Olubenga Bello
Sewa R. Singal
Subodh Verma
Andrew T. Yan
Kim A. Connelly
Publikationsdatum
23.01.2021
Verlag
Springer Milan
Erschienen in
Acta Diabetologica / Ausgabe 5/2021
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-020-01661-y

Weitere Artikel der Ausgabe 5/2021

Acta Diabetologica 5/2021 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Ist Fasten vor Koronarinterventionen wirklich nötig?

Wenn Eingriffe wie eine Koronarangiografie oder eine Koronarangioplastie anstehen, wird häufig empfohlen, in den Stunden zuvor nüchtern zu bleiben. Ein französisches Forscherteam hat diese Maßnahme hinterfragt.

Typ-2-Diabetes: Ernährungsunsicherheit vervierfacht Risiko für schwere Hypoglykämien

04.06.2024 Typ-2-Diabetes Nachrichten

Wenn ältere Menschen mit Typ-2-Diabetes Schwierigkeiten beim Beschaffen und Zubereiten von Mahlzeiten haben, geht dies mit einem deutlich gesteigerten Risiko für schwere Hypoglykämien einher.

Mehr Brustkrebs, aber weniger andere gynäkologische Tumoren mit Levonorgestrel-IUS

04.06.2024 Levonorgestrel Nachrichten

Unter Frauen, die ein Levonorgestrel-freisetzendes intrauterines System (IUS) verwenden, ist die Brustkrebsrate um 13% erhöht. Dafür kommt es deutlich seltener zu Endometrium-, Zervix- und Ovarialkarzinomen.

GLP-1-Agonist Semaglutid wirkt kardio- und nephroprotektiv

03.06.2024 Semaglutid Nachrichten

Der GLP-1-Agonist Semaglutid hat in der FLOW-Studie bewiesen, dass sich damit die Progression chronischer Nierenerkrankungen bei Patienten mit Typ-2-Diabetes bremsen lässt. Auch in kardiovaskulärer Hinsicht war die Therapie erfolgreich.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.