Linagliptin in patients with type 2 diabetes and cardiovascular and/or renal disease: results from a cardiovascular and renal outcomes trial

Figures & data

Table 1. Summary of CVOTs of DPP4 inhibitors in patients with T2DM.

CVOT	Comparators	Participants randomized (N)	Characteristics of study population	Median duration of follow up (years)	Primary outcomes	CV outcomes	HF outcomes	Kidney outcomes
SAVOR-TIMI 53 [8]	Saxagliptin versus placebo	16,492	History of or at risk for CV events	2.1	CV death, MI, or stroke	No increased risk of ischemic events	Increased risk of HHF with saxagliptin (HR 1.27; 95% CI, 1.07 to 1.51)	Not designed to study kidney outcomes
EXAMINE [9,34]	Alogliptin versus placebo	5,380	Recent acute coronary syndrome	1.5	CV death, MI, or stroke	No increased risk of MACE	No significant difference (HR 1.07; 95% CI, 0.79 to 1.46)	Not designed to study kidney outcomes
TECOS [10]	Sitagliptin versus placebo	14,671	Existing CVD	3.0	CV death, MI, UA, or stroke	No increased risk of MACE	No increase in risk of HHF	Not designed to study kidney outcomes
CAROLINA [16]	Linagliptin versus glimepiride	6,042	Early T2DM and risk factors for or established atherosclerotic disease	6.3	CV death, MI, or stroke	No increase in risk of composite CV outcome	No significant difference (HR 0.90; 95% CI, 0.74 to 1.08)	Not designed to study kidney outcomes
CARMELINA [12,13]	Linagliptin versus placebo	6,979	High risk of CV and kidney events	2.2	CV death, MI, or stroke	No increase in risk of composite CV outcome	No increase in risk of HHF	No increased risk of composite kidney endpoint*; significant reduction in albuminuria progression

*Composite kidney endpoint of time to first occurrence of sustained end-stage kidney disease, renal death (adjudicated death due to kidney disease), or a sustained decrease of ≥40% in estimated glomerular filtration rate from baseline.

CI, confidence interval; CV, cardiovascular, CVD, cardiovascular disease, T2DM, type 2 diabetes mellitus, HF, heart failure, HHF, hospitalization for heart failure; HR, hazard ratio; MACE, major adverse cardiovascular events;

MI, myocardial infarction; UA, unstable angina.

Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–1326.

 PubMed Web of Science ®Google Scholar

White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–1335.

 PubMed Web of Science ®Google Scholar

Zannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015;385:2067–2076.

 PubMed Web of Science ®Google Scholar

Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232–242.

 PubMed Web of Science ®Google Scholar

Rosenstock J, Kahn SE, Johansen OE, et al. Effects of linagliptin vs glimepiride on major cardiovascular outcomes in patients with type 2 diabetes: The CAROLINA randomized clinical trial. JAMA. 2019. DOI:10.1001/jama.2019.13772.

 Web of Science ®Google Scholar

McGuire DK, Alexander JH, Johansen OE, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139:351–361.

 PubMed Web of Science ®Google Scholar

Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321:69–79.

 PubMed Web of Science ®Google Scholar