Comparison of gliclazide vs linagliptin on hypoglycemia and cardiovascular events in type 2 diabetes mellitus: A systematic review

Table 3 Gliclazide ± metformin and linagliptin ± metformin (no comparator)

Ref./treatment	Primary study objective	Study design	Study population	CVD excluded	Number of participants	Study duration	Endpoint (hypoglycemia)	Hypoglycemia definition	Hypoglycemia results	Endpoint (MACE)	MACE definition	MACE results
Barnett et al[33], 2008/DINAMIC 1/Gliclazide	Compare the efficacy, tolerability and acceptability of gliclazide in SMBG vs non-SMBG group	Multicenter randomized parallel-group	T2D patients managed on diet alone	Not mentioned	610	6 mo	Safety endpoint (AE)	Grade 1: Suspected mild hypoglycemia	SMBG group: 8.7% patients had 51 HE: symptomatic (27), asymptomatic (11), SMBG-confirmed (11) and non-graded (2)	-	-	-
								Grade 2: Suspected moderate hypoglycemia	Non-SMBG group: 7.0% patients had 66 HE: Symptomatic (66) and non-graded (2). Two HE-related withdrawals
								Grade 3: Suspected severe hypoglycemia with need of third party assistance	No grade 3 or 4 symptoms
								Grade 4: Suspected severe hypoglycemia with need of medical assistance	Symptoms suggestive of nocturnal hypoglycemia: SMBG group: 3 and non-SMBG group: 7
Ross et al[42], 2015/Linagliptin/metformin vs linagliptin monotherapy	Change from baseline in HbA1c	Randomized, double-blind, active-controlled, parallel group, multinational	Newly diagnosed (≤ 12 mo) T2D and marked hyperglycemia (≥ 8.5 and ≤ 12.0%)	ACS, stroke or TIA < 3 mo	316	24 wk	Safety endpoint (AE)	Severe hypoglycemia: Requiring assistance from another person to administer carbohydrate or other resuscitative action	Linagliptin/metformin: 1.9% of patients and linagliptin: 3.2% of patients no severe hypoglycemia	-	-	No deaths

ACS: Acute coronary syndrome; AE: Adverse event; CVD: Cardiovascular disease; DINAMIC: Diamicron MR in NIDDM: Assessing Management and Improving Control; HbA1c: Glycosylated hemoglobin; HE: Hypoglycemic event; MACE: Major adverse cardiovascular event; SMBG: Self-monitoring of blood glucose; T2D: Type 2 diabetes; TIA: Transient ischemic attack.