No increased risk of hospitalization for heart failure for patients treated with dipeptidyl peptidase-4 inhibitors in Taiwan

: Dipeptidyl peptidase-4 inhibitors (DDP-4Is) or gliptins have been extensively studied in recent years. These studies have shown the safety and efficacy of gliptins in managing hyperglycemia in diabetic patients. However, there is ongoing debate on whether DDP-4Is are associated with a higher risk for developing heart failure. It is expected that long-term data from patients who are currently prescribed DDP-4Is will provide a clearer understanding of their potential benefits. This should also help guide the development of future guidelines. The focus of this perspective is on associations between the “use of DPP-4Is” and “increased risk of heart failure”. Thus, we examine several key publications and reviews on clinical trials on this class of oral antidiabetic medications. For this communication, the pertinent literature has been critically analyzed to provide an evidence-based overview of the evolving concept of DPP-4Is-induced risk of heart failure.

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The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: a ten-year prospective observational study

BMC Endocrine Disorders ◽

10.1186/s12902-021-00689-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Vaia Lambadiari ◽

Aikaterini Kountouri ◽

Foteini Kousathana ◽

Emmanouil Korakas ◽

Georgios Kokkalis ◽

...

Keyword(s):

Bullous Pemphigoid ◽

Prospective Observational Study ◽

Dipeptidyl Peptidase ◽

Dermatology Department ◽

Steroid Administration ◽

Dipeptidyl Peptidase 4 ◽

Increased Risk ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

A Prospective Study

Abstract Background Bullous pemphigoid is the most common bullous chronic autoimmune skin disease. Recent studies have suggested dipeptidyl-peptidase 4 inhibitors as possible predisposing agents of bullous pemphigoid. The objective of our study was to prospectively estimate the association between gliptins and the development of bullous pemphigoid. Methods We conducted a prospective study which included all patients diagnosed with biopsy-proven bullous pemphigoid in the Dermatology Department of our hospital between April 1, 2009 and December 31,2019. The diagnosis of bullous pemphigoid was based on specific clinical, histological and immunological features. Results Overall 113 consecutive patients (age 75 ± 13 years, 62 females) with the diagnosis of bullous pemphigoid were enrolled. Seventy-six patients (67.3%) suffered from type 2 Diabetes and 52 (46%) were treated with dipeptidyl-peptidase 4 inhibitors. The most frequent prescribed gliptin was vildagliptin, being administered to 45 cases (39.8% of total patients enrolled, 86.5% of the patients treated with gliptins). Gliptins were withdrawn immediately after the diagnosis of bullous pemphigoid, which together with steroid administration led to remission of the rash. Conclusions This study revealed that treatment with dipeptidyl-peptidase 4 inhibitors, especially vildagliptin, is significantly associated with an increased risk of bullous pemphigoid development.

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Dipeptidyl Peptidase-4 Inhibitors and the Risk of Heart Failure

Circulation ◽

10.1161/circulationaha.118.038399 ◽

2019 ◽

Vol 139 (3) ◽

pp. 362-365 ◽

Cited By ~ 8

Author(s):

Faiez Zannad ◽

Patrick Rossignol

Keyword(s):

Heart Failure ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitors

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Dipeptidyl peptidase-4 inhibitors and cardiovascular and renal disease in type 2 diabetes: What have we learned from the CARMELINA trial?

Diabetes and Vascular Disease Research ◽

10.1177/1479164119842339 ◽

2019 ◽

Vol 16 (4) ◽

pp. 303-309 ◽

Cited By ~ 10

Author(s):

Nordin MJ Hanssen ◽

Karin AM Jandeleit-Dahm

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Side Effect ◽

Dipeptidyl Peptidase ◽

Safe Alternative ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

Favourable Safety ◽

Favourable Safety Profile

Dipeptidyl peptidase-4 inhibitors are a relatively new class of oral anti-hyperglycaemic drugs to treat type 2 diabetes through prevention of degradation of incretins by the dipeptidyl peptidase-4 enzyme. The large trials evaluating the dipeptidyl peptidase-4 inhibitors sitagliptin, alogliptin and saxagliptin demonstrated safety for cardiovascular disease. Post hoc analyses on renal endpoints yielded similar findings. Linagliptin is the latest dipeptidyl peptidase-4 inhibitor evaluated in the CARMELINA trial. CARMELINA included individuals with type 2 diabetes and high cardiovascular and renal risk. Even in this setting, linagliptin displayed cardiovascular safety. CARMELINA also removed initial concerns for heart failure as a class-specific side-effect of dipeptidyl peptidase-4 inhibitors, as no signal for heart failure was found. Although numerically low, CARMELINA did confirm increased rates of pancreatitis in the linagliptin group, suggesting that pancreatitis is a class-specific side-effect of dipeptidyl peptidase-4 inhibitors. Linagliptin reduced progression of albuminuria, but had no effect on other hard renal endpoints. Overall, dipeptidyl peptidase-4 inhibitors are safe but do not confer significant reductions in complications observed for some of the other new glucose-lowering drugs. However, linagliptin is a safe alternative in renal impairment, without dose adjustment. Furthermore, dipeptidyl peptidase-4 inhibitors may hold value as alternatives to sulfonyl-urea derivatives or as an add-on therapy to delay insulin prescription given their favourable safety profile.

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