Diabetic medications with benefit in cardiac patients

In the past 1-2 years, strong evidence from randomized clinical trials has shown that certain diabetic medications have benefits in cardiac patients, including improved survival [1-3]. One of these medication classes is Sodium glucose co-transporter 2 (SGLT2inhibitors. The DAPA-HF trial showed the benefit of Dapagliflozin [1], EMPEROR trial showed the benefit of Empagliflozin [2] and CANVAS trial showed the benefit of Canagliflozin [3]. Long-term pharmacologic therapy in patients with heart failure with reduced ejection fraction and chronic kidney disease has been evaluated and proved to have survival benefits and reduce the disease progression through multiple mechanisms. In this blog, we will discuss some of the SGLT-2 inhibitors data, doses in diabetes and heart failure, and some of their common side effects.

Mechanism of action: SGLT2- inhibitors ( -gliflozin ) reduce blood glucose by increasing urinary glucose excretion and they reduce the risk of progression of diabetic kidney disease.

 

Agent name

 

Dose in heart failure patients

 

Usual dose for Diabetes Melleitus

 

Initial eGFR to initiate drug therapy

 

 

Side effects

 

 

 

Empagliflozin

 

 

 

 

10 mg once daily

With/without DM

 

 

 

 

10-25 mg once daily ,  taken with or without food

 

 

 

≥45 ml/minute/ 1.73 m2

 

 

 

-Vulvo-vaginal candidiasis

 

-urinary tract infections

 

-bone fractures

 

-thirst and Increased urine out put

 

– hypovolemia / reduced systolic pressure

 

-acute kidney injury

 

-increased risk of lower limb amputation

 

– DKA

 

-Necrotizing fasciitis (Fournier gangrene)

 

– long-term safety not established

 

 

 

 

Dapagliflozin

 

 

 

 

10 mg once daily

With/without DM

 

 

 

 

5-10 mg once daily , taken with or without food

 

 

 

≥45 ml/minute/ 1.73 m2

 

 

 

 

 

 

Canagliflozin

 

 

 

 

100 mg once daily

With type 2 DM

 

 

 

100-300 mg once daily , taken with or without food

 

 

 

≥30 ml/minute/ 1.73 m2

 Table 1: Summary of the doses, acceptable GFR and side effects of SGLT-2 inhibitors.

Abbreviations: GFR (Glomerular Filtration Rate), DKA (Diabetic Ketoacidosis)

     Contraindications and precautions — SGLT2 inhibitors should be avoided in the following clinical settings

  • Presence of type 1 DM.
  • Presence of type 2 DM with prior diabetic ketoacidosis (DKA) or a condition predisposing to DKA (including pancreatic insufficiency, drug or alcohol addiction).
  • Volume depletion or symptomatic hypotension.
  • eGFR <30 ml per minute per 1.73 m2(except for empagliflozin, for which the threshold is <20 ml per minute per 1.73 m2), end-stage kidney disease, or rapidly declining renal function.
  • Presence of the following conditions :
  • Frequent bacterial urinary tract infections or genitourinary yeast infections. •Presence of risk factors for foot amputation (including those with neuropathy, foot deformity, vascular disease, and/or history of previous foot ulceration).

In conclusion, SGLT-2 inhibitors have shown to have benefits in heart failure with reduced ejection fraction and chronic kidney disease. Health care practitioners, including primary care doctors, cardiologists, endocrinologists, nephrologists, clinical pharmacists and nurse practitioners among other members of the health care team, should familiarize themselves with these medications and their doses in order to provide the best care to our patients.

A special thank you to my sister, Rawan Ya’acoub, a clinical pharmacist and assistant professor at the University of Jordan, who helped me write this blog.

References:

  • McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19. PMID: 31535829.

 

  • Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. doi: 10.1056/NEJMoa2022190. Epub 2020 Aug 28. PMID: 32865377.

 

  • Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12. PMID: 28605608.

 

 

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