. 2015 May;12(3):164–174. doi: 10.1177/1479164115570301

Table 1.

Key inclusion criteria in CAROLINA.

Insufficient glycaemic control	Elevated risk of CV events defined as any 1 (or more) of the criteria (a, b, c or d)
(a) HbA1c 6.5%–8.5% while patient is treatment naive 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% 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 specimens in the previous 12 months (iii) Proliferative retinopathy defined as retinal neovascularisation or previous retinal laser coagulation therapy (c) Age ⩾ 70 years (d) At least two of the following CV risk factors: (i) T2D 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

Insufficient glycaemic control

Elevated risk of CV events defined as any 1 (or more) of the criteria (a, b, c or d)

(a) HbA1c 6.5%–8.5% while patient is treatment naive 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% 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 specimens in the previous 12 months
- (iii) Proliferative retinopathy defined as retinal neovascularisation or previous retinal laser coagulation therapy
(c) Age ⩾ 70 years
(d) At least two of the following CV risk factors:
- (i) T2D 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

CAROLINA: CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes; IC: informed consent; T2D: type 2 diabetes; BP: blood pressure; SU: sulphonylurea; MI: myocardial infarction; MDRD: modified diet in renal disease; eGFR: estimated glomerular filtration rate; CV: cardiovascular.