Table 1.

Key inclusion criteria CAROLINA®

Insufficient glycaemic control defined as one of the criteria (A or B)	AND	Elevated risk of cardiovascular events defined as any (one or more) of the criteria (A, B, C or D)
(A) HbA1c 6.5 - 8.5% (48–69 mmol/mol) while patient is treatment naïve or treated with:  (I) Metformin monotherapy  (II) α-Glucosidase inhibitor monotherapy (e.g. acarbose, voglibose)  (III) Metformin plus α-glucosidase inhibitor (e.g. acarbose, voglibose)  (B) HbA1c 6.5 - 7.5% (48–58 mmol/mol) while patient is treated with:  (I) SU monotherapy  (II) Glinide monotherapy (e.g. repaglinide, nateglinide)  (III) Metformin plus SU (for a maximum of 5 years)  (IV) Metformin plus glinide (for a maximum of 5 years)  (V) α-Glucosidase inhibitor plus SU (for a maximum of 5 years)  (VI) α-Glucosidase inhibitor plus glinide (for a maximum of 5 years)		(A) Previous vascular disease: (I) MI (>6 weeks prior to informed consent IC) (II) Documented coronary artery disease (⩾50% luminal diameter narrowing of left main coronary artery or in at least two major coronary arteries in angiogram) (III) Percutaneous coronary intervention (>6 weeks prior to IC) (IV) Coronary artery bypass grafting (>4 years prior to IC) or with recurrent angina following surgery (V) Ischaemic or haemorrhagic stroke (>3 months prior to IC) (VI) Peripheral occlusive arterial disease (B) Evidence of vascular-related end-organ damage: (I) Moderately impaired renal function (as defined by MDRD formula) with eGFR 30–59 ml/min/1.73 m2 (II) Random spot urinary albumin:creatinine ratio ⩾30 μg/mg in two of three unrelated specimens in the previous 12 months. (III) Proliferative retinopathy defined as retinal neovascularization or previous retinal laser coagulation therapy (C) Age ≥ 70 years (D) At least two of the following cardiovascular risk factors: (I) T2DM duration >10 years (II) Systolic BP > 140 mmHg (or on at least 1 BP-lowering treatment) <6 months prior to IC (III) Current daily cigarette smoking (IV) LDL-cholesterol ⩾ 135 mg/dL (3.5 mmol/L) (or specific current treatment for this lipid abnormality) <6 months prior to IC

Table adapted from Marx et al. 2015 [21]. CAROLINA: CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes; IC: informed consent; T2DM: type 2 diabetes mellitus; BP: blood pressure; SU: sulphonylurea; MI: myocardial infarction; MDRD: modified diet in renal disease; eGFR: estimated glomerular filtration rate